1- A new drug is being developed to treat COPD.

It has been found to be safe in healthy volunteers, and seems effe tive in small-s ale trials in patients. !he effe ts of the drug are short-lived when it is withdrawn. What is the most appropriate design for the next phase of trials? Case- ontrol study Cohort study Double-blind rossover "C! Double-blind parallel groups "C! Open-label parallel groups "C! A randomised controlled trial (RCT) is the gold standard for evaluating a new intervention The drug has !een found to !e safe" so an open#la!el trial is unnecessar$% a dou!le#!lind trial reduces the potential for !ias The dou!le#!lind parallel groups RCT would !e a suita!le design &owever" a crossover design is more powerful if the disease to !e treated is chronic and sta!le" and there is little ris' of carr$#over effects (continued action of the drug after it is withdrawn) These conditions are met" and so the !est answer is dou!le#!lind crossover RCT (#Which of the following statements !est descri!es a t$pe#( error? "is# of a false-positive result Alpha error "is# of dete ting a treatment differen e when there is none "is# of not dete ting a signifi ant differen e when there is one $one of the above A t$pe#( or !eta error occurs when the null h$pothesis is wrongl$ accepted" ie a false#negative )or example" in a clinical trial" a t$pe#( error has occurred when the stud$ fails to detect a significant difference !etween the two drugs on trial when in fact there is one This can happen if the sample si*e is too small +tudies therefore have to have ade,uate power to find a difference if one exists )ormulae are availa!le to help wor' out the minimal sample si*e re,uired -#Which statement !est descri!es a crossover trial? Drugs with long-term effe ts are typi ally used %a h patient re eives only one drug %a h patient will usually re eive all drugs within the study Patients are always blinded to whi h drug they are re eiving &elf-limiting illnesses are easily studied .n a crossover trial" the patient (who usuall$ has a chronic sta!le disease) receives one drug (or place!o) and after a washout period" the other .n this Correct answer Correct answer Correct answer

wa$" confounding can !e greatl$ reduced .f a drug had long#lasting effects it ma$ not !e eas$ to see which of the trial drugs was having an effect A self#limiting illness is difficult to stud$ in this wa$ test is used to ompare the mean height in two populations. A random sample is ta#en from ea h population and the differen e in sample means is 1' m, with a ()* onfiden e interval from +, m to ,, m. /#.f the true means in the two populations are 012 cm and 031 cm" which one of the following statements is correct? !he test shows we an be ()* sure there is a differen e !here is no differen e in height between the two populations A type-1 error has o A type-, error has o urred urred Correct answer

A paired t-test should have been used The correct test to compare the means of two different populations is an unpaired t#test We have !een told the true means and the$ are different" so option 4 is incorrect The 516 confidence interval for the difference in means includes *ero" so the test has not detected a significant difference The null h$pothesis (no difference in means) is false" !ut the test has not re7ected it% this is a t$pe#( error &owever" if the null h$pothesis were true and the test re7ected it" this would !e a t$pe#0 error )-A team of onsultants has identified a set of 1' lini al symptoms they believe may help an insuran e ompany predi t how long a person will be off wor# after suffering whiplash in-ury in a ar a ident. %a h symptom is assessed separately as ' . absent, 1 . present. !o determine e/a tly how useful these 1' symptoms are, ,'' patients with whiplash in-uries were assessed within 0 days of their a ident and then followed up until all had returned to wor#. Which of the following methods is !est for anal$sing the results from this stud$? 1ultiple linear regression &eries of one-way analyses of varian e, with time off wor# as the out ome 2dependent3 variable and ea h symptom in turn as the predi tor 2independent3 variable Paired t-test omparing time off wor# with total symptom s ore Pearson orrelation oeffi ient of total symptom s ore against time off wor# &pearman orrelation oeffi ient of total symptom s ore against time off wor# The !est option is A 8xcept for C (which is invalid)" the other options can also !e used" !ut are less desira!le A paired t#test compares a single measure (varia!le) recorded on a single Correct answer

group of individuals on two different occasions .n this instance" two different measures are !eing anal$sed" al!eit measured on the same individuals Clearl$" therefore" option C is invalid The total score (ie total num!er of s$mptoms present) is used in options 9 and 8 as the potential predictor of time off wor' This is fine if it can !e reasona!l$ assumed that each s$mptom is e,uall$ important and thus can !e given e,ual weight in the prediction .n which case" a :earson correlation (option 9) would !e valid if either the total score or time off wor' can !e assumed to follow a ;ormal distri!ution < !ut if !oth measures are non# ;ormal" +pearmans correlation coefficient (option 8) must !e used &owever" the assumption of e,ual weight is unnecessaril$ simplistic" so these options are pro!a!l$ su!optimal The series of one#wa$ anal$ses of variance suggested !$ option 4 attempt to loo' at the predictive a!ilit$ of each s$mptom separatel$" so is argua!l$ !etter than using the total scores &owever" this is a piecemeal anal$sis" which cannot easil$ indicate the relative importance of each s$mptom +$mptoms with the highest level of statistical significance are pro!a!l$ most predictive < !ut are the$ independentl$ predictive (ie do the$ provide different information in a prediction) and what weights should !e allocated to each s$mptom? =ption A answers !oth of these important ,uestions" so is optimal A multiple regression anal$sis with time off wor' as the outcome (dependent) varia!le and all 02 s$mptoms as predictor (independent) varia!les" will determine which of the s$mptoms significantl$ < and" importantl$" independentl$ < predict time off wor' The regression coefficients will also provide estimates of the relative weight of each s$mptom in the prediction )or example" if the regression coefficient for s$mptom > is dou!le that of the coefficient for s$mptom ?" the weights allocated to s$mptoms > and ? when calculating total scores should reflect this =rdinar$ linear regression ma$ !e accepta!le since all patients were followed up until the$ returned to wor' &owever" it ma$ !e more sensi!le to use Cox regression as this is designed specificall$ for the anal$sis of time to an event occurring This would also allow the stud$ to !e terminated earl$ if some patients had not returned to wor' when the stud$ had to end (ie had a ver$ severe in7ur$)" as it can correctl$ handle censored data !reatment 4 is li ensed as an effe tive treatment for lung an er. !he pharma euti al ompany that mar#ets treatment 4 believes it has a benefi ial effe t on 5uality of life. 6efore embar#ing on a full-s ale randomised ontrolled trial, the ompany tested its hypothesis in an open study restri ted -ust to patients pres ribed treatment 4. %a h patient ompleted a validated 5uality-of-life s ale at the start of treatment and then 1, months later. !he s ale gives integer values between ' and )'7 s ores above 8' are onsidered to be desirable. Which of the following methods is !est for presenting the results from this stud$? Change in the proportion of patients with s ores above the desired ut-off level, with its ()* onfiden e limits Chi-s5uare test and p-value for pre- and post-study proportions above the desired ut-off level Average hange in s ale s ores, with its ()* onfiden e limits

Correct answer

1ean s ores at the start and end of the treatment period, with their standard deviations 9npaired t-test statisti and p-value only 8xcept for 4 (which is invalid)" the other options can also !e used" !ut are less desira!le Reducing scores from a continuous scale to a !inar$ (dichotomous) measure is rarel$ optimal statisticall$ The primar$ anal$sis of this ,ualit$#of#life scale should !e !ased on the actual scores &owever" an evaluation of the proportions of patients a!ove and !elow the desired cut#off point ma$ provide an informative secondar$ anal$sis < in which case" option A should !e used =ption 4 can !e used onl$ for comparing independent groups The patients in the pre# and post#stud$ groups are the same people (ie the samples are dependent)" so the appropriate significance test is the @c;emar test% the Chi#s,uare test is invalid A significance test statistic and its p#value will indicate the extent to which the changes in ,ualit$#of#life scores were consistent across patients 8ven assuming that the scores follow a ;ormal distri!ution" option 8 provides ver$ limited information% appropriate summar$ statistics are also needed to ,uantif$ the degree of change that occurred .f the scores are ;ormall$ distri!uted" mean scores at the start and end of the stud$ can !e used (option 9) &owever" standard deviations onl$ provide information a!out the extent to which the scores varied !etween individual patients at the two assessments% information on the varia!ilit$ in the change scores would !e more useful &ence" option C is optimal Confidence intervals can !e computed for either the mean or median change" depending on the distri!ution of the scores .f the confidence interval does not contain the value *ero (the result that would occur if the treatment does not affect ,ualit$#of#life scores)" the change can !e accepted as statisticall$ significant @ore importantl$" the confidence interval indicates the most li'el$ range of values for the true population effect of treatment > on ,ualit$ of life" so is much more informative than a significance test :-A )-year, randomised ontrolled trial to ompare two treatments for redu ing the ris# of a se ondary 1I has -ust ended. %ligible patients were randomised to one of the treatments ; wee#s after the initial 1I. It re5uired , years to re ruit the number of patients needed to give the study ade5uate power. All patients were followed up either to re-infar tion or to the end of the study. !he proportions of patients with reinfar tions were 1,* and 1:* for treatments A and 6, respe tively. Which of the following methods is !est for anal$sing the results from this stud$? Chi-s5uare test of re-infar tion proportions Co/ proportional ha<ards regression 1ann+=hitney 9-test of median times to re-infar tion 9npaired t-test of mean times to re-infar tion Correct answer

>ogisti regression ;one of the other options should !e considered seriousl$ Aiven the wa$ in which the ,uestion is worded" the most o!vious anal$sis appears to !e option A (the Chi#s,uare test) &owever" not all patients have !een studied for the same length of time :atients recruited near the start of the stud$ will have !een followed up for almost 1 $ears% those enlisted later ma$ have !een followed up for !arel$ - $ears Randomisation ma$ even this out to a degree" !ut the total follow#up times in the two stud$ groups will still !e une,ual 4ecause option A reall$ re,uires a fixed follow#up time for all patients" it can !e onl$ !e used here if the stud$ period is restricted to the time for which the last patient recruited was followed up =ption 8 suffers from the same pro!lem The outcome (dependent) varia!le in a logistic regression is whether or not the outcome of interest (re#infarction) has occurred" so a fixed follow# up period is needed .ncluding time of follow#up as a predictor (independent) varia!le would seem to !e an o!vious wa$ round this < effectivel$" this is what option 4 does" !ut in a more effective wa$ statisticall$ Times to an event rarel$ follow a ;ormal distri!ution" so comparing means with a t#test is inappropriate" as this does rel$ on the varia!les !eing normall$ distri!uted @ore importantl$" onl$ a!out 0/6 of the patients recruited have experienced the event of interest" so mean or median times to re#infarction cannot !e computed" ma'ing options C and 9 invalid The Cox (proportional odds) regression method was devised specificall$ for this t$pe of stud$ in which man$ patients fail to reach the end#point (ie in statistical terms" are censored) and in which follow#up time varies 4oth issues are dealt with specificall$ in the mathematical theor$ underl$ing the method" ma'ing option 4 the onl$ sensi!le option 0-An on ologist has gained the impression that many women diagnosed as having breast an er also have high levels of wor#-related stress. What t$pe of design would !e the most practical to test this possi!le association? ?roup omparative, randomised ontrolled trial Cross-over, randomised ross-over trial Prospe tive ohort study "etrospe tive ase- ontrol study Prospe tive observational study Although the !est option is 9" some of the other answers could !e considered .n this context" a randomised controlled trial (RCT) of an$ description (options A and 4) would !e wholl$ inappropriate < and pro!a!l$ unethical" as it would involve randomising women to low# or high#stress 7o!s and then waiting to see how man$ develop !reast cancer )rom a strict scientific viewpoint" this is the !est wa$ to esta!lish a causal association < !ut the ideal is Correct answer

not alwa$s accepta!le A prospective o!servational stud$ (option 8) is also inappropriate =!servational surve$s are used primaril$ to measure a single characteristic of interest in a population .f the o!7ective is to loo' for (causal) associations !etween two or more characteristics (as is the case here)" a slightl$ different approach is needed =ption C (a prospective cohort stud$) is similar in most respects to the simple surve$ offered !$ option 8 An important difference is that the stud$ population is divided at the start of the stud$ into those individuals exposed to the ris' factor (in a high#stress 7o!) and those who are not (in a low#stress 7o!) 4oth groups (cohorts) are followed up for an appropriate period and the incidence of the outcome of interest (!reast cancer) compared !etween the two groups This is the next !est scientific approach to esta!lishing association when an RCT cannot !e underta'en Bnfortunatel$" the design has two ma7or disadvantagesC it would ta'e a considera!le length of time to complete (pro!a!l$ in excess of 02 $ears in this case) and would involve huge num!ers of women (as the incidence of !reast cancer is small) .n practice" option 9 < a retrospective case#control stud$ < is optimal Women who have suffered the outcome (have 7ust !een diagnosed as having !reast cancer) are identifiedC these are the cases 8ach case is matched with at least one woman of the same age and demographic characteristics who have not suffered the outcome (have not !een diagnosed as having !reast cancer)C these are the controls The proportions of cases and controls exposed to the ris' factor (have a high#stress 7o!) are compared This design re,uires a relativel$ small num!er of participants and can !e completed within a short time < !ut it does re,uire retrospective recall of important data !$ the participants ;evertheless" it is the !est option for this stud$ @-In a small double-blind study of pain following dental surgery, patients are randomly allo ated to re eive either an analgesi tablet or a mat hing pla ebo tablet 1 hour preoperatively. All patients were as#ed to rate their pain at ; hours after surgery using the following s aleA ' . nil, 1 . mild, , . moderate, 8 . severe. What is the !est statistical test for anal$sing the results of this stud$? Chi-s5uare test One-way analysis of varian e 1ann+=hitney 9-test Bisher e/a t test 9npaired &tudent t-test Although the !est answer to this ,uestion is C" all the other answers have some virtue :ain is measured here using an ordinal categorical scale )re,uentl$" such scales are considered to !e continuous (more correctl$" pseudo#continuous) and the literature contains man$ instances of this practice .f this approximation is made then options 4 or 8 are !oth appropriate tests < one#wa$ anal$sis of Correct answer

variance is identical mathematicall$ to the unpaired +tudent t# test when 7ust two groups are !eing compared &owever" approximating to a continuous scale is pro!lematic hereC there are onl$ four points on the scale% each point is given a specific definition% and the distances !etween the points are unli'el$ to !e e,ual (moving from moderate to mild will not !e the same as moving from mild to moderate) +trictl$" !oth tests also re,uire the data to follow a ;ormal(Aaussian) distri!ution < this is unli'el$ with a short ordinal scale =ptions 4 and 8 are thus the least desira!le =ptions A and 9 are also effectivel$ the same test 4oth ta'e the extreme opposite view to that adopted a!ove and treat the pain scale as !eing wholl$ categorical (ie nominal) This" too" has some reason to it" and examples can !e seen in the literature The )isher exact test is mathematicall$ ver$ complex and" even with modern computer power" can ta'e a long time to compute The Chi#s,uare test is an approximation to the )isher exact test" which is !ased on a ver$ much simpler alge!raic formula that can !e computed in a few moments with 7ust a simple calculator &owever" the scale is specificall$ designed to have an ordering to it" and it is inefficient to ignore this =ptions A and 9 are !etter than 4 and 8" !ut still not optimal =ption C is a non#parametric test" which does not assume an$ underl$ing distri!ution for the data !ut does ta'e account of the ordering across the scale points There is a statistical pro!lem in that man$ o!servations will !e the same (ie tied)" !ut as the stud$ is descri!ed as small this should not !e a ma7or concern There is no ideal anal$sis for this stud$ < !ut option C ma'es the !est use of the data and the least du!ious assumptions a!out the statistical properties of the pain scale 5#Regarding statistical methodolog$" which of the following statements is most applica!le? !he median and mean do not differ even when the population distribution is s#ewed 1ean refers to the value that o urs with the highest fre5uen y !he value of CrD 2 oeffi ient of variation3 ranges from -1 to E1 In iden e is defined as the number of ases seen in the population at any given time !he probability that a given result ould have been obtained purely by han e is higher when the p-value is '.'1 rather than '.') :revalence is defined as the num!er of cases seen in the population at an$ given time The value occurring with the highest fre,uenc$ is the mode The lower the p#value" the lower the possi!ilit$ that the result is due to chance 02#Which of the following statements is most appropriate regarding the relative ris' of a disease? Always lies between <ero and one Correct answer

Is always positive 1easures the in reased 2or de reased3 ris# of the fa tor when the individual has the disease 1easures the ris# of the disease in the population !a#es the value <ero when the ris# is e5ually li#ely in those e/posed and une/posed to the fa tor of interest

Correct answer

The relative ris' is alwa$s positive" !ut it can ta'e a value that is greater than one .t measures the increased (D 0) or decreased (E 0) ris' of the disease if the factor is present compared to when it is a!sent and is the ratio of two ris's in the population The relative ris' ta'es the value one (unit$) when the ris's in those with and without the factor are e,ual 00#Which of the following descri!es the standard deviation of a set of o!servations? It is a measure of the pea# values of the data It is the s5uare root of the varian e It is a measure of spread, whi h is e5ual to the range It is not affe ted by outliers It is an appropriate measure of spread for s#ewed data The standard deviation is a measure of the spread of the data and is calculated as the s,uare root of the variance .t is different from the range" which is also a measure of spread The standard deviation is a sort of average of the deviations of each o!servation from the mean" whereas the range is simpl$ the difference !etween the largest and smallest o!servations The standard deviation is affected !$ outliers and would !e larger than expected if outliers are present .f the data are s'ewed" the standard deviation will tend to overestimate the spread in the data 0(#Which is the most characteristic feature of an ogive? !he first per entile has ((* of the observations in the ordered set below it !he first de ile is e5ual to the ('th per entile and has 1'* of the observations in the ordered set below it !he mean is e5ual to the )'th per entile !he range is the differen e between the 1st and ((th per entiles !he inter5uartile range lies between the first and third 5uartiles Correct answer Correct answer

An ogive is a continuous cumulative fre,uenc$ curve The first percentile has 556 of the o!servations in the ordered set a!ove it" not !elow it The first decile is e,ual to the 02th percentile (not the 52th percentile)" although it does have 026 of the ordered o!servations !elow it The median is e,ual to the 12th percentile The range is the difference !etween the largest and smallest o!servations 0-#What does the p#value refer to?

!he probability that the null hypothesis is true !he probability that the alternative hypothesis is true !he probability of having in orre tly re-e ted the null hypothesis !he probability of obtaining the observed results or results whi h are Correct more e/treme if the null hypothesis is true answer A value that is always less than '.') The null h$pothesis is either true or false The p#value must relate what is in the sample to what is in the population The alternative h$pothesis is either true or false .t is the pro!a!ilit$ of o!taining the o!served or more extreme results if the null h$pothesis is true The cut#off of 2 21 is usuall$ used to indicate significance" !ut the p#value can ta'e an$ value !etween 2 and 0 0/#Which of the following is a characteristic of sampling? A sample statisti is a point estimate of a population parameter &ampling error arises when we trans ribe data in orre tly $o riteria for sample sele tion are involved in random sampling Bor a set of observations, the standard deviation is always less than the standard error of the mean !he inferential pro ess involves drawing on lusions about the sample +ampling error arises when onl$ a portion of the population is studied Random sampling implies that the sample has !een selected from a sampling frame in such a wa$ that ever$ individual has the same chance of !eing selected .n random sampling" defined criteria for sample selection are laid down The standard error of the mean is the standard deviation divided !$ the s,uare root of the sample si*e" hence it must alwa$s !e smaller than the standard deviation .nference is the process of drawing conclusions a!out the population using the sample information 01#Regarding statistical definitions" which of the following statements is true? $ull hypothesis des ribes the probability that a relationship e/ists between two samples Analyti al statisti s are the same as inferential statisti s Des riptive statisti s do not provide mean values from data !he mode is the measurement that lies e/a tly between ea h end of a range of values ran#ed in order &#ewed data invalidates further statisti al analysis The null h$pothesis sets out the assertion that a relationship !etween two samples does not exist" anal$tical statistical methods set a!out disproving the null h$pothesis" ie demonstrating a relationship 9escriptive statistics provide mean" median and mode values for a distri!ution The mode is the most commonl$ o!served value% the median is the measurement that lies exactl$ !etween each end of a range of values ran'ed in order Correct answer

Correct answer

03#Which of the following is a characteristic of confidence intervals? !he intervals are smaller with a smaller sample si<e !hey indi ate the presen e or otherwise of a statisti al differen e between two groups A ()* onfiden e interval means that there is only a )* han e that the true mean value for the variable lies outside the ranges 5uoted In an odds ratio, if the ()* onfiden e interval in ludes unity, then this indi ates a signifi ant differen e !he narrower the onfiden e interval, the greater the signifi an e

Correct answer

Confidence intervals descri!e the range of values around a mean" an odds ratio" a p#value or a standard deviation within which the true value lies A narrow confidence interval emphasises the significance of the result" !ut it is the p#value that descri!es significance" not the confidence interval around it 0F#The results of a statistical stud$ were expressed as followsC R G H2 3F" p E 2 0 D 2 21 Which of the following options applies? A negative "-value indi ates an inverse asso iation " stands for standard oeffi ient A positive "-value indi ates la # of asso iation !his study indi ates there is a strong asso iation p F '.1 G '.') is signifi ant A positive R#value means that as one varia!le increases" so does the other A negative R#value means that as one varia!le decreases" the other increases i e the correlation is inversed An association or lac' of association is indicated !$ how close the value of R is to *ero and its statistic significance is denoted !$ its p#value .n this stud$" the R#value is positive" indicating association &owever" this association does not seem to !e statisticall$ significant as the p#value is greater that 2 21 :#values E 2 21 are considered to !e significant 0I#Regarding definitions of true# and false#positive and #negative rates" which of the following is true? !he true-positive rate is the same as spe ifi ity !he false-negative rate is al ulated as 21 + sensitivity3 A perfe t test would have a sensitivity of at least 0'* !he false-positive rate is al ulated as 2false-positiveHItrue-positive E false-positiveJ3 !he true-negative rate is 21 + false-negative rate3 The true#positive rate" ie the sensitivit$" provides a measure of how well the test correctl$ identifies patients with disease The true#negative rate" i e the specificit$" reflects how well the test correctl$ identifies patients without disease The true#negative rate is calculated as (0 < false#positive Correct answer Correct answer

rate) The false#positive rate is the proportion of negative instances that were erroneousl$ reported as !eing positive This is calculated as (false# positiveJ(total num!er of negative instances) G false positiveJ(true negative H false negative) A perfect test should have a sensitivit$ of 0226 and a specificit$ of 0226 1(-In a randomised ontrolled trial of alternative treatments for ysti fibrosis, the primary out ome variable is hange in lung fun tion. It is e/pe ted that the response will be affe ted by the severity of the disease, the age of the patient, the entre at whi h the patient is treated and the baseline level of lung fun tion. .n the +tatistical Anal$sis :lan it is most important that? !he trial is analysed by an analysis of ovarian e that in orporates Correct only the variables spe ified above answer !he trial is analysed by an analysis of ovarian e that in ludes all variables that are statisti ally signifi ant at the )* level !he hanges in lung fun tion are analysed using the unpaired &tudent t-test &ubgroup analyses are performed for all the variables e/pe ted to affe t the hange in lung fun tion >ung fun tion measurements are standardised for age, se/ and height prior to any other analysis .t provides an efficient anal$sis without introducing !ias =ption 4 can give results that are misleadingl$ precise through what is" in effect" multiple testing" and the :#value can !e distorted =ption C is a valid test" !ut a ver$ inefficient test +u!group anal$ses should !e used sparingl$ and onl$ with varia!les expected to modif$ the treatment effect" so 9 is wrong +tandardised lung function measurements can !e useful in epidemiological studies" !ut are unnecessar$ in a trial where change in lung function is !eing examined" so 8 is incorrect (2#.f two new screening tests for colon cancer and for pancreatic cancer are introduced" !oth of the tests have the same sensitivit$ and specificit$" and the$ are applied to the general population aged !etween 11 and 35 $ears" then which of the following statements would !est appl$? 6oth tests will have the same positive predi tive value, and both tests will have the same negative predi tive value !he positive predi tive value for the olon an er test will be higher and the negative predi tive value for the olon test will be higher !he positive predi tive value for the olon an er test will be higher Correct and the negative predi tive value for the pan reati test will be higher answer !he positive predi tive value for the pan reati an er test will be higher and the negative predi tive value for the pan reati an er test will be higher !he positive predi tive value for the pan reati an er test will be higher and the negative predi tive value for the olon an er test will be higher The easiest wa$ to chec' the possi!ilities is to ma'e up a numerical example with chosen sensitivit$ and specificit$" and with two different

prevalence rates .f sensitivit$ G 516" specificit$ G 526" and we compare prevalences of 06 and 16 and loo' at the expected num!ers in 02"222 su!7ects" we haveC :revalence G 06 :ositi ;egati Tot ve ve al Cases 51 Contr 552 ols 1 I502 022 552 2

:ositive predictive value G 51J(552 H 51) ;egative predictive value G I502JI501 :revalence G 16 :ositi ;egati Tot ve ve al Cases /F1 Contr 512 ols (1 I112 122 512 2

:ositive predictive value G /F1J(/F1 H 512) (higher than !efore) ;egative predictive value G I112JI1F1 (lower than !efore) Whatever prevalence we choose" the higher prevalence will have the higher ::K and the lower ;:K As colon cancer is more common than pancreatic cancer" C is correct (0#.f the prevalence of Rett s$ndrome is 0 per 02"222 and a genetic screening test applied in infanc$ has a sensitivit$ of 526 and a specificit$ of 55 556" then !he positive predi tive value is less than )'* and the negative predi tive value is greater than ((.((* !he positive predi tive value is less than )'* and the negative predi tive value is less than ((.((* !he positive predi tive value is greater than )'* and the negative predi tive value is greater than ((.((* !he positive predi tive value is greater than )'* and the negative predi tive value is less than ((.((* !he positive predi tive value and the negative predi tive value annot both be al ulated Correct answer

To see this" ta!ulate the expected num!ers in a population" which" to ma'e the num!ers easier" we will ta'e as 0"222"222C

Test positive Rett ;on# Rett Total 52 L022 052

Test negative 02 L555"I22 555"I02

Total 022 555"52 2 0"222"2 22

We form the column of totals first from the prevalence of Rett s$ndrome" and then use the sensitivit$ applied to the first row and specificit$ applied to the second row to o!tain the ta!ulated num!ers (we actuall$ expect 55 55H tests in the non#Rett population) The positive predictive value is therefore 52J052 (E 126) The negative predictive value is 555"I22J555"I02 (D 55 556) ,,-In an age-Hse/-mat hed, ase- ontrol study, ,' hildren with hroni asthma were ompared with ,' ontrols from the same general pra ti e. !heir birthweights were ompared using a paired t-test. !his showed that the ontrols were 1)' g heavier with a standard error of 1'' g. Which is the most appropriate conclusion? A lower birthweight auses an in reased in iden e of asthma 6irthweight is not asso iated with the subse5uent development of asthma !here is a statisti ally signifi ant asso iation 2P F '.')3 between low birthweight and the development of asthma !here is insuffi ient eviden e to on lude whether or not birthweight Correct affe ts the development of asthma answer !he study design is inappropriate The fairl$ negative option 9 is the most appropriate conclusion )rom association in an o!servational stud$" we cannot infer cause and effect" so option A must !e wrong +tatement 4 is stronger than the stud$ 7ustifies The fact that a significant association has not !een shown in this stud$ does not impl$ that in a larger stud$ an association might not !e found =ption C is incorrect as the ratio of the difference in weights" divided !$ its standard error" is onl$ 0 1" and therefore : D 2 21 )inall$" the stud$ design would !e perfectl$ reasona!le for the purpose and therefore option 8 is incorrect ,8-In an observational study of ,'' patients with asthma, for ed vital apa ity 2BKC3 was measured at the start and end of a )-year period. Potential predi tors of a hange in BKC were re orded at the start of the )-year period. A orrelation oeffi ient of '.8 2P F '.')3 was reported for the orrelation of asthma duration and hange in BKC after ) years. Which of the following is the most appropriate conclusion? In reasing duration of asthma auses a greater rate of loss of lung fun tion Duration of asthma does not have a signifi ant effe t on rate of hange in lung fun tion

?reater rate of de line in lung fun tion is signifi antly asso iated with a shorter duration of asthma 6igger rates of redu tion in BKC tend to be seen in patients with a longer duration of asthma 6e ause of possible onfounding, no on lusions an be formed

Correct answer

.n answering this ,uestion care has to !e ta'en with the directions of the associations Remem!er that a decline in lung function corresponds to a negative change in )KC and the correlation is positive Thus option C is correct A is incorrect" !oth through impl$ing cause and effect and also !ecause the direction of the association is wrong =ption 4 is misinterpreting the :#value" which does show a significant association 9 is also interpreting the direction of the association incorrectl$ Although in such an o!servational stud$ confounding is possi!le" it does not mean that conclusions from such a stud$ cannot !e made and therefore 8 is incorrect ,;-In a ross-se tional study of :'' hildren, mental ability s ores were al ulated from a standardised test. !he orrelation between lead in their blood and their ability s ore was reported as r . +'.'), P F '.'). What does this show? %/tra patients should be re ruited and randomised to the treatments in su h a way that a balan e in mean age is a hieved Ligher levels of lead in the blood are asso iated with lower ability Correct s ores answer !he asso iation between lead in the blood and ability s ore is li#ely to be due to han e !he null hypothesis for the signifi an e test is that lead in the blood is asso iated with lower ability s ores !he probability that lead in the blood affe ts the ability s ore is more than ()* =ption A is incorrectl$ concluding cause and effect from an association in an o!servational stud$ =ption C is misinterpreting the given :#value The onl$ h$pothesis !eing tested is that lead in the !lood and a!ilit$ scores are not associated" so 9 is incorrect =ption 8 is a wa$ in which significance tests are often classicall$ misinterpreted ,)-In a ross-over trial omparing two drugs to treat hildren suffering from enuresis, the number of dry nights was re orded in ea h of two ,@-day periods of treatment. Which of the following strategies for anal$sis is the most appropriate? Constru t a ontingen y table with the number of dry nights forming the olumns, and the treatments forming the rows, and apply a Chi-s5uared test Bor ea h hild, identify the treatment produ ing the greater number of dry nights, and apply an appropriate test of signifi an e to test the null hypothesis that the proportion of Cpreferen esD for ea h treatment is the same Apply a paired t-test if the differen es in the number of dry nights are Correct appro/imately symmetri al, otherwise apply a =il o/on &igned "an# answer

&um !est Apply a non-parametri test to ompare the distribution of the number of dry nights for the two treatments Cal ulate the orrelation oeffi ient between the number of dry nights on ea h treatment, and test for a signifi ant orrelation .n a cross#over trial it would !e sensi!le to allow for the possi!ilit$ of an order effect in the data" !ut none of the options allows for this The answers are therefore not perfect for the ,uestion posed !ut the !est answer is C .f there is no order effect" this would !e a good method of anal$sing the data =ption A ignores the pairing and would therefore !e a poor method of anal$sis =ption 4 is a reasona!le approach !ut" !ecause it is compressing the data" would !e less efficient than option C =ption 9 ignores the pairing and should not !e chosen for that reason =ption 8 would not answer the relevant ,uestion as correlation !etween the responses to the two treatments is of no interest here (3#.n a randomised controlled trial of treatments for heart failure in which the primar$ end#point is death" which is the most important of the following? !o have an independent Data 1onitoring Committee to review the Correct data as it a umulates answer Bor the trial statisti ian to e/amine the data whenever a death o urs and stop the trial as soon as the log ran# test shows P F '.') !o have a learly defined set of rules for a se5uential analysis of the data, and only to stop the trial if it is indi ated by this analysis !he !rial &teering Committee should be #ept aware of the results throughout the trial !o ensure that all patients have a minimum of 8 monthsD follow-up before in lusion in the analysis =ption 4 is a classical mista'e to ma'e where the data is tested repeatedl$ without ta'ing into account the multiple testing of the data that is implied =ption C gets round this pro!lem" !ut to suggest that the trial would onl$ !e stopped on this !asis is inappropriate as other factors" such as intolera!le adverse effects of treatment" would also need to !e considered" as would results from other newl$ pu!lished studies .t is considered good practice for the Trial +teering Committee to !e unaware of the results as the trial progresses" and therefore 9 is wrong =ption 8 sounds plausi!le !ut is an unusual restriction and is indeed undesira!le @an$ patients ma$ die within the first - months of treatment and therefore this option would !e inappropriate ,0-In a randomised, ontrolled, parallel group trial to ompare two treatments for lowering blood pressure, omparison of the mean ages at the time of randomisation shows an average differen e of 8 years between the two treatments. A t#test shows that the difference is highl$ significant (: E 2 20) !his should be ignored as we #now the allo ation to treatment was at randomisation An analysis should be underta#en to see if the imbalan e alters the

Correct

on lusions of the trial !he validity of the trial is ompromised !he patients should have been stratified by age when underta#ing the randomisation %/tra patients should be re ruited and randomised to the treatments in su h a way that a balan e in mean age is a hieved

answer

.m!alance in a !aseline varia!le will inevita!l$ sometimes occur in well# conducted" randomised controlled trials Bnder such circumstances the approach descri!ed in option 4 is a sensi!le one to choose =ption A is plausi!le" !ut good practice would not allow what might !e an important difference in !aseline varia!les to !e simpl$ ignored The im!alance ma$ !e a nuisance in interpretation !ut it certainl$ does not invalidate the trial" so C is incorrect =ption 9 sounds li'e !eing wise after the event and adopting this approach would ensure !alance !$ age &owever" it ma$ not !e of great importance in relation to response to treatment" and therefore it would not alwa$s !e sensi!le to stratif$ !$ age as suggested in 9 =ption 8 is undou!tedl$ the worst of the five answers ,@-In a group of @' sub-e ts, measurements of diastoli blood pressure 2D6P3 are found to be appro/imately normally distributed with a mean of 0; mmLg and a standard deviation of : mmLg. Which of the following statements is most li'el$ to !e true? Appro/imately ;' sub-e ts will have D6P levels between :@ mmLg and @' mmLg !here will be ;' sub-e ts with measured D6P levels higher than 0; mmLg and ;' patients with measured levels lower than 0; mmLg Appro/imately 18 sub-e ts will have a measured D6P level that is less Correct than :@ mmLg and , will have a 6P whi h is above @: mmLg answer $obody will have a D6P level of (' mmLg or higher Appro/imately ,0 sub-e ts will have measured D6P levels above @' mmLg Remem!ering that around two#thirds of values lie within 0 +9 of the mean" one#third will therefore lie outside 0 +9" and half of these (one#sixth) will !e less than 0 +9 !elow the mean (ie E 3I mm&g) Thus around I2J3 G 0- are expected to !e E 3I mm&g Around ( 16 will !e higher than ( +9s a!ove the mean (ie I3 mm&g) and so two such cases are expected Therefore approximatel$ 01 will !e E 3I mm&g or D I3 mm&g )or A" around 1- (two# thirds) will !e !etween 3I mm&g and I2 mm&g Although on average half will !e !elow the mean and half a!ove" it is unli'el$ that exactl$ /2 will !e so" ma'ing 4 incorrect As 52 mm&g is ( 3F +9s a!ove the mean" values D 52 mm&g will !e relativel$ uncommon (around 2 16) .t is therefore ,uite possi!le that no!od$ will have a 94: D 52 mm&g" !ut there is still an apprecia!le chance that someone in the group will !e D 52 mm&g" so 9 is less appropriate than C =ption 8 corresponds to one#third !eing a!ove I2 mm&g" whereas the correct fraction is one#sixth (5#.n the design of a randomised controlled trial" to what does the power of the stud$ refer?

!he si<e of treatment differen e that the trial an be e/pe ted to dete t !he probability of re-e ting the null hypothesis that the treatments have the same effe t !he han e that a lini ally signifi ant differen e will be observed !he probability of a type-, error !he probability of a statisti ally signifi ant treatment effe t if the true Correct treatment differen e is at a prespe ified level answer .t uses a specified si*e of treatment difference" !ut A is not correct =ption 4 would !ecome correct if it was extended to sa$ when there is a prespecified treatment difference" !ut is incorrect as it stands C loo's plausi!le" !ut the difference !eing specified in the power calculation might not correspond to a clinicall$ significant difference (the difference might !e set higher) so C is incorrect :ower is often defined as 0 minus the pro!a!ilit$ of a t$pe#( error" so 9 is wrong 8'-A lini al trial was designed to ompare the use of a heater probe plus in-e tion of thrombin versus the use of a heater probe plus pla ebo in-e tion into the bleeding sites of haemorrhagi gastri ul ers. "esults showed 1: out of 1,0 patients re5uired emergen y surgery in the thrombin arm, and 18 out of 1,' patients re5uired emergen y surgery in the pla ebo arm. An appropriate anal$sis would use which of the following? 1 $emarDs test An unpaired t-test Analysis of ovarian e Chi-s5uare test >og-ran# test The correct answer is 9" as the data can !e arranged into a ( M ( contingenc$ ta!le @c;emars test is applied to !inar$ data" !ut is onl$ applica!le to paired data" so A is incorrect The t#tests are applica!le to ,uantitative varia!les" so 4 is also incorrect The same applies to =ption C .f the time to failure of treatment was !eing recorded" 8 would !e possi!le" !ut the ,uestion onl$ reports success or failure" so it is also incorrect -0#.n a parallel group trial" which of the following claims for randomisation is the most appropriate? It guarantees that all variables are well balan ed a ross the treatment groups prior to treatment Any differen es in response found between the treatment groups must be due to the treatments rather than han e It prevents systemati differen es between the treatment groups at baseline It results in a simplified analysis of the trial It ensures that an e5ual number of patients re eive ea h treatment Correct answer

Correct answer

The purpose of randomisation is to prevent s$stematic differences !etween treatment groups" so option C is the correct answer Although we will often get good !alance across the treatment groups" unfortunatel$ randomisation does not guarantee this" so option A is incorrect 8ven if randomisation is underta'en in a trial" this does not guarantee that differences in response found !etween the treatment groups must !e due to the treatment We ma$ still !e unluc'$ and find a false#positive result" so 4 is incorrect We ma$ hope that randomisation leads to a simplified anal$sis of the trial compared to an$ other option !ut it is not the primar$ o!7ective" so 9 would not !e the answer of choice )inall$" randomisation can !e used to ensure an e,ual num!er of patients receive each treatment% however" in some trials we will deli!eratel$ wish to have a randomisation ratio such as -C(" so randomisation does not impl$ e,ual num!ers on each treatment and 8 is incorrect 8,-A ross-over trial is being planned to ompare the effi a y of two drugs in the treatment of rheumatoid arthritis. Which of the following design considerations should $ou adopt? !here should be a run-in period when the patient re eives a pla ebo !he design should be simplified by avoiding randomisation as patients re eive both treatments A washout period, where the patient re eives pla ebo, should ta#e pla e between the administration of the two treatments If either drug is thought to be a disease-modifier, plans to run a ross- Correct over trial should be abandoned answer Only patients who will guarantee to omplete both treatments should be re ruited .f an$ treatment in a cross#over trial is a disease#modifier (in the most extreme case" 'ills or cures the patient)" then the interpretation of results in an$ su!se,uent period !ecomes impossi!le =ption A will ,uite often !e appropriate" !ut there will !e situations when a place!o run#in will !e considered unethical =ption 4 would simpl$ !e !ad practice" as onl$ !$ randomisation of the treatment order can we !e assured that we are guarding ade,uatel$ against !ias A wash#out period !etween treatments is often useful in cross#over trials !ut" as in option A" the use of a place!o treatment will" in some situations" !e unethical Although we would li'e to ensure that all patients who enter trials complete them" the suggestion in option 8 would almost certainl$ !e deemed unethical 88-A randomised ontrolled trial has been ondu ted to evaluate fish-oil apsules against orn-oil apsules 2as a ontrol group3 to determine the antihypertensive effe ts in a group of mild, untreated hypertensive patients. &ow are the results !est summarised? !he signifi an e level of a test to ompare blood-pressure hanges in the two treatment groups &eparate levels of signifi an e for ea h treatment to evaluate whether the blood pressure has been signifi antly redu ed in ea h ase 1eans and standard deviations for the blood pressures before

treatment and after treatment in ea h of the treatment groups 1ean and onfiden e interval for the differen e in redu tion in blood pressure between the two treatments 1eans and onfiden e intervals for the redu tion in blood pressure in ea h of the treatment groups

Correct answer

As the stud$ is controlled" it is the difference !etween the active intervention group and the control that is of importance =ptions C and 8" which relate to the changes within each of the treatment arms" might well !e supplementar$ information !ut would not !e the most important =ption 4 descri!es !ad practice" as separate tests for the two treatment arms are inappropriate =ption A is a perfectl$ reasona!le thing to do and would almost certainl$ !e reported as well as option 9 &owever" it conve$s less information than option 9" which is therefore to !e preferred 8;-A group of ;'' male asthmati s attending a hospital out-patient lini had their for ed vital apa ity 2BKC3 assessed at the start and end of a )-year period. !he mean annual redu tion in BKC was :' ml and the standard error of the mean annual redu tion in BKC was ; ml. Which of the following statements is the most appropriate? ()* of patients had redu tions in BKC between ,:' ml and 8;' ml over a )-year period Almost all patients had a lower BKC at the end of the study, ompared with their level at the beginning ()* onfiden e limits for the mean annual redu tion in BKC are appro/imately ), ml and :@ ml ()* onfiden e limits for the mean annual redu tion in BKC are appro/imately ): ml and :; ml Cal ulation of onfiden e intervals re5uires that the data are normally distributed

Correct answer

The 516 confidence limits will !e the mean plus or minus two standard errors as given in this answer =ption 9 is incorrect !ecause the limits given correspond to the mean plus or minus one standard error The statement 8 is not a necessar$ condition for the calculation of confidence intervals =ption A relates to the distri!ution of individuals within the population" whereas the standard error has !een calculated for a parameter that is the mean =ption 4 loo's convincing" !ut !ac'#calculating from the standard error of the mean to the standard deviation within the population shows that the standard deviation is I2 ml" and therefore an apprecia!le proportion of patients will have increased their )KC 8)-In a study of 1'' normal males aged ;'+;( years, the B%K1 levels were found to be appro/imately normally distributed with a mean value of 8.)' litres, and ()* onfiden e limits for the mean were al ulated as 8.8;+8.:: litres. Which of the following statements is most accurate? )* of sub-e ts will have B%K1 levels less than 8.8; l ,.)* of sub-e ts will have B%K1 levels less than 8.8; l

If another group of normal males of the same age was studied, the sample mean would have a ()* han e of being between 8.8; l and 8.:: l !he ()* onfiden e limits an be used to s reen sub-e ts for abnormal respiratory fun tion !he range of values 8.8;+8.:: l e/ lude the population mean with probability '.')

Correct answer

Confidence intervals relate to values of the population mean and tell $ou how precisel$ $ou have determined the mean Confidence intervals are usuall$ expressed in terms of limits that include the population mean with pro!a!ilit$ 2 51 =ption 8 is stating this in a slightl$ indirect wa$ (meaning that there is a 16 chance that the true population mean is not included in this range" in other words a 516 chance that the true population mean is included within this range) =ptions A and 4 can !e dismissed straight awa$ as the statements refer to su!7ects rather than the population mean +imilarl$" =ption C is a statement a!out the sample mean rather than a statement a!out the population mean =ption 9 is incorrect !ecause limits for an$ varia!le need to !e !ased on the distri!ution of the individuals rather than on confidence intervals for means 8:-!he total ost to the $L& of two treatments for hole yste tomy are to be ompared in the setting of a randomised ontrolled trial. A total of ;' patients have re eived ea h treatment. !he distribution of the osts is seen to be strongly positively s#ewed. Which of the following is the preferred method of anal$sis to assess whether average costs differ significantl$? A paired t-test An independent samples t-test An independent samples t-test applied to the logarithms of the osts A =il o/on &igned "an#s &um !est A 1ann+=hitney 9-test .t might loo' at first sight as though either =ption C or 8 would !e a good answer (as the distri!utions are positivel$ s'ewed) We have to remem!er" however" that the ,uestion relates to comparing costs" and an$ transformation of the data or ran'ing of the data would mean that we were no longer directl$ comparing costs Thus" although option 4 is not the optimal wa$ of anal$sing the data" it is the !est of the five choices offered =ptions A and 9 are inappropriate !ecause the$ onl$ appl$ to paired data 80-In a randomised ontrolled trial to ompare two drugs 2A and 63 for the se ondary prevention of myo ardial infar tion, in the first year there were five deaths in 1'' patients treated with drug A and ten deaths in 1'' patients treated with drug 6. !he results are reported as 4, . 1.1), P . '.,@. Which of the following statements is most appropriate? Correct answer

!here is a ,@* probability that the death rate with drug A is lower at one year than the death rate with drug 6 !here is a 0,* probability that the null hypothesis of e5ual drug effe ts is true !he null hypothesis of e5ual drug effe ts has not been disproved !he two drugs may be onsidered e5uivalent A larger trial would definitely have given statisti ally signifi ant results

Correct answer

!he statisti al signifi an e of a result is the probability 2Mp valueM3 that the observed relationship 2e.g., between variables3 or a differen e 2e.g., between means3 in a sample o urred by pure han e and that in the population from whi h the sample was drawn, no su h relationship or differen es e/ist. !he p value in this ase signifies a ,@* han e of in orre tly re-e ting the null hypothesis 2i.e. the hypothesis that there is no differen e between the , groups, drug A and drug 63. !he fa t that the differen es between the , groups in this ase are non-signifi ant does not imply e5uivalen e between the drugs, and therefore option D is in orre t. A larger trial may or may not have given statisti ally signifi ant results and therefore option % is also in orre t. 8@-After treatment with one of two antihypertension agents in a randomised ontrolled trial 2)' patients per treatment group3, the hanges in diastoli blood pressure appear to be appro/imately symmetri ally distributed within ea h treatment group. Which of the following statements is most appropriate for anal$sis of the trial data? As the results may not be normally distributed, a non-parametri test for independent samples, su h as the 1ann+=hitney 9-test, should be applied As the results may not be normally distributed, a non-parametri test for paired samples, su h as the =il o/on &igned "an# &um !est, should be applied A paired sample t-test should be applied to test the null hypothesis that both treatments produ e the same mean redu tion in diastoli blood pressure An independent sample t-test should be applied to test the null Correc hypothesis that the same mean redu tion in diastoli blood pressure t answer o urs with ea h treatment !he hanges in blood pressure should be assessed as being of lini al signifi an e or not, and a Chi-s5uared test should be applied to ompare the proportions e/perien ing a lini ally signifi ant improvement in diastoli blood pressure The t#test does not re,uire data to !e exactl$ normall$ distri!uted in order for it to !e applied" the test !eing ro!ust The approximatel$ s$mmetrical distri!ution will !e ade,uate to ensure that the test is valid =ption A would not !e chosen !ecause a non#parametric test would give less power =ption 4 is incorrect as the data is not paired and this also applies to =ption C =ption 8 would !e a valid anal$sis to underta'e !ut it would have the ma7or disadvantage that its power would !e far less than =ption 9

8(-In a ohort study of 1''' non-smo#ers and 1''' smo#ers, ;)' of the smo#ers and )' of the non-smo#ers developed COPD. What is the relative ris' of smo'ing for C=:9? ( 1H( @ 1H@ 0 Relative ris' (RR) G (incidence among exposed)J (incidence among unexposed) .ncidence among exposed G /12J0222 G 2 /1 .ncidence among unexposed G 12J0222 G 2 21 RR G 2 /1J2 21 G 5 &everal samples were randomly ta#en from a population for a study. /2#Which of the following statements is correct regarding the sample means and the population mean for the varia!le under stud$? !he distribution of sample means will be negatively s#ewed if the variable is distributed in the population with a positive s#ew !he distribution of sample means will be positively s#ewed if the variable is distributed in the population with a positive s#ew !he mean of the sample means will be different to the population mean if the variable is not distributed normally in the population !he distribution sample means will be normally distributed even if the Correct population values are not normally distributed answer !he standard error of the sample mean is independent of the sample si<e The central limit theorem states thatC The random sampling distri!ution of means would alwa$s tend to !e normal" irrespective of the population distri!ution for which the samples were drawn &ence" even if the population distri!ution is s'ewed or in an$ non#normal distri!ution" the sample means would !e normall$ distri!uted The theorem also states that the mean of the random sampling distri!ution of means is e,ual to the mean of the original population /0#.n addition" the standard deviation of the random sampling distri!ution of means (sx) is e,ual to the standard deviation of the population (s) divided !$ the s,uare root of the si*e of the samples (sx G sJNn) .n a positivel$ s'ewed distri!ution A 1ean in reases, median remains the same, mode in reases 1ean remains the same, median remains the same, mode Correct answer

in reases 1ean in reases, median in reases, mode in reases 1ean remains the same, median remains the same, mode remains the same 1ean in reases, median in reases, mode remains the same

Correct answer

A positivel$ s'ewed distri!ution would have a relativel$ small num!er of ver$ large values .magine a normal distri!ution to which a few o!servations with large values are added This would produce a positive s'ew The mean is the measure of the central tendenc$ that is most sensitive to extreme scores The mode is uninfluenced !$ the small num!er of extreme values as it onl$ indicates the value that occurs most fre,uentl$ in the distri!ution The opposite events would occur in a negativel$ s'ewed distri!ution /(#Which of the following o!servations is ver$ sensitive to extreme scores in a distri!ution? 1ean 1edian 1ode )'th entile All are e5ually affe ted @ean" median and mode are measures of central tendenc$ The$ coincide if the distri!ution of values is normal and the fre,uenc$ pol$gon assumes a !ell#shaped Aaussian distri!ution &owever" with extreme scores" the distri!ution gets s'ewed and the measures ma$ !e affected @ode is the o!served value that occurs at the greatest fre,uenc$ in a distri!ution and is totall$ uninfluenced !$ a small num!er of extreme scores The median is the o!servation that divides the fre,uenc$ distri!ution !$ half and is e,ual to the 12th centile .t responds to the num!er of extreme o!servations !ut not their value" and therefore is useful as a measure of central tendenc$ in extremel$ s'ewed distri!utions The mean is the average value of o!servations" and therefore ver$ sensitive to extreme values in a distri!ution /-#What is the t$pe#0 error most closel$ related to? Correlation oeffi ient !he p value Positive predi tive value &tandard deviation &tandard error of the mean A t$pe#0 or alpha error occurs when the null h$pothesis is falsel$ re7ected .n other words" a significant difference is found !etween two drugs when" in actual fact" there is none" and instead the result has occurred !$ chance A p value of 2 21 indicates there is a pro!a!ilit$ of 1J022 (0 in (2) that the result ma$ have occurred !$ chance Correct answer Correct answer

;;-A trial was ondu ted to loo# for oagulation abnormalities in patients with tuber ulosis. &erum fibrinogen levels were ta#en as a riterion to diagnose oagulation abnormalities. !he sub-e ts were divided into three groups + those without tuber ulosis, those with pulmonary tuber ulosis and those with disseminated fulminant tuber ulosis. !he mean fibrinogen level was al ulated for ea h group of patients and ompared for signifi ant differen e between the groups. /1#Which of the following tests would !e ideal for this measurement? Chi-s5uare test &tudentDs t test "egression analysis A$OKA Pearson test The appropriateness of a test to examine a statistical pro!lem depends upon the scale of measurement (nominal" ordinal" interval" ratio) and the t$pe of ,uestion !eing as'ed The Chi#s,uare test is used for nominal data to find out if there is a significant difference !etween the proportion of o!servations falling in each group < for example" comparing the proportion of children developing measles !etween a group receiving a new measles vaccine and a group not given the vaccine The +tudents t test is used to compare one or two means" whereas A;=KA (anal$sis of variance) is used for more than two means" as in this scenario The :earson test is used to assess the correlation (strength of association) !etween two varia!les" whereas regression techni,ues are used to predict the value of one varia!le !ased on the other /3#Which of the following statements !est descri!es the standard deviation? It is derived from the p value It is derived from the 2varian e3, It is a measure of how lose the sample mean is to the population mean It is a measure of the spread of the sample distribution Its numeri al value is 1.(: The standard deviation (+9) indicates the spread of a distri!ution of o!servations A greater +9 represents a greater spread of values .t is derived from the s,uare root of the variance The standard error is a measure of how close the sample mean is to the population mean .f the sample were normall$ distri!uted" 3I6 of the values would lie within O 0 +9 a!out the mean and 516 of the values would lie within O 0 53 +9s a!out the mean /F#Which of the following t$pes of studies have the greatest pro!lems with recall !ias? Case- ontrol studies Correct answer Correct answer

Correct answer

Cohort studies Crossover trials "andomised ontrolled trials &ystemati reviews A case#control trial studies groups of people with an illness and compares them with control su!7ects to tr$ and identif$ a causal factor" !ut !iases ma$ creep into their interpretation of past events Cohort studies follow su!7ects through time and" while potentiall$ time#consuming" the$ have less recall !ias 9ou!le#!linding helps to remove !ias from !oth the patient and researcher +tatisticians anal$sing data from randomised controlled trials should also !e !linded +$stematic reviews can !e confounded !$ the authors own pre7udice" or !ias in searching" selecting and interpreting evidence /I#Which one of the following groups is arranged as nominal scale data? LotH old LotHhotterHhottest @1+('H(1+1''H1'1+11' NC ,01+,@'H,@1+,('H,(1+8'' #elvin $one 9ata alwa$s come in one of the four scales of measurementC ;omin 9ata are divided into ,ualitative groups" such as hotJcold" with no al implication of order 9ata are placed in an order (hotJhotterJhottest)" although the =rdin a!solute levels are un'nown and no conclusion can !e made a!out al the si*e of the interval 9ata are placed in an order% and the exact value of the measurement is given" usuall$ in measured ,uantities representing the difference !etween two measurements (I0<52J50<022J020<002 PC) That is" differences !etween ar!itrar$ pairs of measurements can !e .nterv meaningfull$ compared Ratios !etween num!ers on the scale are not al meaningful" so operations such as multiplication and division cannot !e carried out directl$ 4ut ratios of differences can !e expressed% for example one difference can !e twice another .f the measurement scale does not have an a!solute *ero (i e no num!ers exist !elow the *ero) this is called interval data Ratio &ere" there is a value of 2 'elvin" and it isnQt possi!le to get !elow this (i e a!solute *ero)" therefore the ratio !etween the values is meaningful" eg (F0<(I2J(I0<(52J(50<-22 'elvin Correct answer

/5#A child is !eing monitored for !od$ weight and it has !een determined that its current weight is in the /2th centile This means thatC It is ;'* as heavy as the average weight of hildren of that age group in the population

It is :'* as heavy as the average weight of hildren of that age group in the population ;'* of the hildren of that age group in the population weigh less than this hild :'* of the hildren of that age group in the population weigh less than this hild It is ;'* as heavy as the heaviest hild of that age group in the population

Correct answer

Centile ran's provide a wa$ of giving information a!out an individual score in relation to all the other scores in a population .f all the values for a varia!le in a population were arranged in order" a particular percentage of o!servations would !e !elow it )or example" the (1th centile would !e the value at which (16 of o!servations would !e less than that value A practical application of centile ran'ings is in monitoring the growth of children 12#Which of the following !est descri!es a positivel$ s'ewed distri!ution? 1ean, median and mode lie at the same point 1ean lies to the left of the mode 1ean lies to the left of the median 1ean annot be reliably al ulated 1ean lies to the right of the median Correct answer

.f a distri!ution is as$mmetric it is either positivel$ s'ewed or negativel$ s'ewed A distri!ution is said to !e positivel$ s'ewed if the scores tend to cluster toward the lower end of the scale (that is" the smaller num!ers) with increasingl$ fewer scores at the upper end of the scale (that is" the larger num!ers) .n other words" the long slope of the curve is in the positive direction (i e longer tail on the right" in the higher values) When the varia!le is s'ewed to the left (i e negativel$ s'ewed) the mean shifts to the left the most" the median shifts to the left the second most" and the mode the least affected !$ the presence of the s'ew in the data Therefore" when the data are negativel$ s'ewed" this happensC mean E median E mode When the varia!le is s'ewed to the right (i e " positivel$ s'ewed)" the mean is shifted to the right the most" the median is shifted to the right the second most" and the mode the least affected Therefore" when the date are positivel$ s'ewed" this happensC mean D median D mode 10#.n a sample from a normal distri!ution" what statistic !est descri!es the precision with which the population mean can !e estimated? Coeffi ient of variation &#ewness

&tandard deviation &tandard error Karian e A 516 confidence interval for the population mean is given !$ the sample mean 0 53 times the standard error" so the standard error determines the precision with which the mean can !e estimated (ie a smaller standard error leads to a narrower confidence interval) The standard deviation and the variance (which is the standard deviation s,uared) descri!e the variation across the population The coefficient of variation (the standard deviation divided !$ the mean) is an appropriate measure for distri!utions where all values are positive" so it is not appropriate here The s'ewness descri!es how as$mmetrical the distri!ution is < the normal distri!ution is s$mmetrical so it has a s'ewness of *ero ),-!wenty-three onse utive adult patients attending a dermatology outpatientsD lini with atopi dermatitis are assessed with the si/ area, si/ sign, atopi dermatitis 2&A&&AD3 s ore. !he mean &A&&AD s ore is found to be ,@ with a ()* onfiden e interval of ,:.) to ,(.). Which of the following statements !est descri!es the interpretation of the 516 confidence interval? ()* of the entire 9O adult population will have an &A&&AD s ore between ,:.) and ,(.) ()* of patients in this population have an &A&&AD s ore between ,:.) and ,(.) ()* of the patients in the sample of ,8 had an &A&&AD s ore between ,:.) and ,(.) =e are ()* onfident that the mean &A&&AD s ore in the 9O adult population is between ,:.) and ,(.) =e are ()* onfident that the mean &A&&AD s ore in this population Correct is between ,:.) and ,(.) answer The 516 confidence interval for the mean is an interval that has a 516 chance of containing the true value of the mean for this population (ie the population of all adult patients attending a dermatolog$ outpatients clinic with atopic dermatitis) The 516 confidence interval tells us a!out the precision with which we can estimate the mean" and not a!out the distri!ution of individual values in the sample We certainl$ cannot draw conclusions a!out the entire BR population from these results" which onl$ appl$ to atopic dermatitis outpatients )8-In a ertain population, total holesterol has a normal 2?aussian3 distribution, with )* of values being less than ; mmolHl and )* of values over 0 mmolHl. What are the mean" median and mode of total cholesterol in this population? 1ean . ; mmolHl7 median . ; mmolHl7 mode . ; mmolHl Correct answer

1ean . ; mmolHl7 median . ).) mmolHl7 mode . 0 mmolHl 1ean . ).) mmolHl7 median . 1.) mmolHl7 mode . 0 mmolHl 1ean . ).) mmolHl7 median . ).) mmolHl7 mode . ).) mmolHl 1ean . ).) mmolHl7 median . ).) mmolHl7 mode . 0 mmolHl The normal distri!ution is a s$mmetrical !ell#shaped distri!ution" and as with all s$mmetrical unimodal distri!utions" the mean" median and mode are all e,ual We 'now that 16 of values are !elow / mmolJl and 16 a!ove F mmolJl" and as the distri!ution is s$mmetrical" the midpoint (corresponding to the mean" median and mode of the distri!ution) must !e halfwa$ !etween these two points The mean" median and mode are therefore all 1 1 mmolJl );-Investigators hypothesise that lower staffing levels in intensive therapy units 2I!9s3 at night may lead to worse out omes for patients admitted at night than those admitted during the day. An observational ohort study of all I!9 admissions is planned to investigate this hypothesis. Which would !e the !est method to control for selection !ias in anal$sing the results of this stud$? 6linding Case-mi/ 2ris#3 ad-ustment Double-data entry "andomisation "epeated measurement +election !ias occurs when the chance of !eing assigned a particular treatment depends on factors that are lin'ed to the outcome )or example" if patients who are at higher ris' of d$ing are more li'el$ to receive a new treatment then a stud$ comparing the ris' of death in patients receiving the new treatment to those who are not will !e !iased against the new treatment The !est wa$ to remove selection !ias is through randomisation &owever" this is not possi!le in some cases We cannot randomise the time when patients are admitted to .TB" !ut we can control the anal$sis for 'nown confounding factors < this is called case#mix (or ris') ad7ustment )or example" patients admitted to .TB following elective surger$ are 'nown to !e at ver$ low ris'% the$ are also more li'el$ to !e admitted during the da$ than the night We should therefore include surgical status as an explanator$ varia!le in the model 4linding (which controls o!server !ias) can also !e ruled out as it is impossi!le in this situation 9ou!le#data entr$ will improve the accurac$ of the data and repeated measurements will improve the precision" !ut neither can affect selection !ias Correct answer Correct answer

))-In a trial of a new drug ompared to standard therapy, the ris# of ompli ations in the ontrol arm is ,.;* and the ris# of ompli ations in the treatment arm is 1.@*. What is the a!solute ris' reduction associated with the new treatment? '.:* 1.@* ,.;* ,)* 88* A 'e$ ,uestion needed to interpret the results of a clinical trial is whether the measured effect si*e is clincall$ important Three commonl$ used measures of effect si*e are relative ris' reduction (RRR)" a!solute ris' reduction (ARR)" and the num!er needed to treat (;;T) to prevent one !ad outcome A!solute ris' reduction is 7ust the a!solute difference !etween the control group event rate (C8R) and the event rate in the experimental group (88R)C this can !e expressed as the formula C8R # 88R The a!solute ris' reduction in the example used in this ,uestion is therefore difference in ris' !etween the control arm and the treatment arm" !eing ( /6 minus 0 I6 G 2 36 The other commonl$ used measure is the relative ris' reduction" which measures how much the ris' is reduced in the experimental group compared to a control group This is calculated as the a!solute ris' reduction expressed as a percentage of the ris' in the control arm ((C8R # 88R)JC8R)" in this case 2 3J( / or (16 Relative ris' reduction is often more impressive than a!solute ris' reduction )urthermore" the lower the event rate in the control group" the larger the difference !etween relative ris' reduction and a!solute ris' reduction !he mean age of patients admitted to a ute hospitals in the 9O is reported to be )) years. !he re ords of 1'' onse utive admissions to a single hospital are being e/amined to test whether admissions to this hospital are older or younger than average. !he mean age of the 1'' admissions is )@ years, with a standard deviation of 10 years. A one-sample t-test is used to ompare this to the national average and is reported as Ct . 1.0:, p . '.'@D. 13#What conclusion can !e !est drawn from this test using a 516 confidence level? !he mean age of admissions to this hospital is )) years !he mean age of admissions to this hospital is )@ years !he mean age of admissions to this hospital is not e5ual to )) years =e annot re-e t the hypothesis that the mean age is )) years =e annot re-e t the hypothesis that the mean age is )@ years Correct answer

Correct answer

The o!served mean of 1I $ears is consistent (at the 516 confidence level) with the h$pothesised mean of 11 $ears This is shown !$ the p#value" which is greater than 2 21 A sample of admissions is not sufficient to ena!le us to draw definite conclusions a!out all admissions < the mean age of all admissions to this hospital is unli'el$ to !e exactl$ 11 or exactl$ 1I A positive test result (p E 2 21) would have ena!led us to conclude that the mean age is not e,ual to 11 $ears The h$pothesis that was !eing tested was that the mean age of admissions is 11 $ears < we cannot draw an$ conclusions relating to other h$potheses (eg that the mean age is 1I $ears) 1F#&ow would $ou !est descri!e the statistical !enefit of increasing the sample si*e of a stud$ comparing two treatments? A larger sample si<e de reases the probability of a type-1 error A larger sample si<e ensures that the sample must be representative of the population A larger sample si<e produ es more pre ise estimates A larger sample si<e removes the need for randomisation A larger sample si<e will in rease the magnitude of the differen e between the two treatments The pro!a!ilit$ of a t$pe#0 error (re7ecting the null h$pothesis when it is true) is the significance level" which is fixed in advance (often at 16) .ncreasing the sample si*e reduces the standard error" meaning the estimate is more precise and the pro!a!ilit$ of a t$pe#( error (not re7ecting the null h$pothesis when it is false) is reduced ;o matter how large the sample is" we can never !e certain that it is representative of the population Randomisation is still necessar$ with large sample si*es !ecause the sample si*e does not affect !iases such as selection !ias The sample si*e does not affect the magnitude of the treatment difference" !ut it will ma'e us more li'el$ to !e a!le to detect a given difference as a result of the increased precision 1I#.f all mem!ers of a population each have an independent pro!a!ilit$ of (16 of carr$ing a certain disease" what is the distri!ution of the num!er of people carr$ing the disease in a random sample of 0( people drawn from this population? 6inomial with n . 1,, p . '.,) Chi-s5uared with 8 degrees of freedom Poission with lambda. 8 $ormal with mean . 8, standard deviation . 1.) 9niform with p . 1H1, The !inomial distri!ution descri!es the num!er of times an event occurs from a fixed num!er of opportunities when the pro!a!ilit$ that the event occurs at each opportunit$ is constant and independent The distri!ution is characterised !$ the num!er of opportunities (n) and the pro!a!ilit$ of an Correct answer

Correct answer

event (p) .n this case" the opportunities are the sampled mem!ers of the population" and an event is carr$ing the disease )(-A group of patients attending an outpatients lini have their systoli blood pressure measured before and after their appointment, and are as#ed to grade their satisfa tion with the appointment. !he variables re orded areA 2i3 se/, 2ii3 initial blood pressure, 2iii3 end blood pressure and 2iv3 satisfa tion rating 2graded A for satisfied, 6 for neutral and C for dissatisfied3. What are the scales of measurement of each of these different varia!les? 2i3 $ominal, 2ii3 ontinuous, 2iii3 ontinuous, 2iv3 ordinal 2i3 $ominal, 2ii3 ontinuous, 2iii3 ordinal, 2iv3 nominal 2i3 $ominal, 2ii3 ordinal, 2iii3 ordinal, 2iv3 ordinal 2i3 Ordinal, 2ii3 ontinuous, 2iii3 ordinal, 2iv3 ontinuous 2i3 Ordinal, 2ii3 ontinuous, 2iii3 ontinuous, 2iv3 nominal A nominal varia!le consists of categories that have no natural order% an ordinal varia!le consists of ordered categories% a continuous (or scale) varia!le has meaningful numeric values that can !e added and su!tracted +ex is a nominal varia!le as we cannot sa$ that male D female or female D male The satisfaction rating is an ordinal varia!le as the responses can !e ordered !$ the amount of satisfactionC A D 4 D C 4oth the initial !lood pressure measurement and the end !lood pressure are continuous varia!les :'-A study shows a signifi ant positive asso iation between i e- ream sales and the number of ases of severe sunburn presenting at an AP% department. Which of the following is the most li'el$ explanation for this association? Cause and effe t Coin iden e Common ause Confounding Correlation 4oth ice#cream sales and cases of sun!urn increase as a result of hot and sunn$ weather < this is a common cause .t would !e wrong to conclude that ice#cream causes sun!urn As we can find a plausi!le reason for the association" there are no grounds to conclude it is coincidence There is no o!vious confounding factor !etween ice#cream and sun!urn An example of confounding would !e a stud$ comparing a new pain#relief ta!let to no treatment < the effect of the drug is confounded with the place!o effect" where 7ust giving the patient an$ ta!let ma$ improve their perception of the pain Correlation is another term for association (often linear association) and as such is not an explanation of the Correct answer Correct answer

association :1-A study e/amines the relationship between blood pressure and age using linear regression. !he result is reported as the e5uationA Q . @1.8 E 1.847 where Q is systoli blood pressure in mmLg and 4 is age in years. &ow would $ou !est descri!e the interpretation of the regression coefficient of 0 -? A ()* onfiden e interval for the mean systoli blood pressure in this population is @1.8 R 1.8 mmLg On average, age in reased by 1.8 years for every additional 1-mmLg in rease in systoli blood pressure On average, systoli blood pressure in reased by 1.8 mmLg for every Correct additional year of age answer !he average systoli blood pressure measurement must be multiplied by 1.8 for every additional year of age !he range of systoli blood pressures observed in this population was @1.8 1.8 mmLg The regression e,uation allows us to predict an average s$stolic !lood pressure given a patients age +o" for example" a patient aged /2 would have a predicted s$stolic !lood pressure of 0-- - mm&g (I0 - H S0 - M /2T) and a patient aged 12 would have a predicted s$stolic !lood pressure of 0/3 - mm&g (I0 - H S0 - M 12T) The intercept term" I0 -" tells us the predicted s$stolic !lood pressure at age *ero" although this would not !e a relia!le prediction as it is li'el$ to !e outside the age range of the population in the stud$ The coefficient" 0 -" tells us how much" on average" the s$stolic !lood pressure increases for each additional $ear of age < ie an increase of 0 - mm&g ever$ $ear Patients presenting with a sudden onset of severe o ipital heada he have a 1'* han e of having had a subara hnoid haemorrhage 2&AL3. 3(#.f a computed tomograph$ (CT) scan has 526 sensitivit$ for detecting +A&" lum!ar puncture (U:) following a negative CT has 556 sensitivit$ and !oth have perfect specificit$" then what is the pro!a!ilit$ that a patient who tests negative on !oth CT and U: has had an +A&? 1H(1 1H('1 1H(''1 1H(1 E 1H('1 1H(1 S 1H('1 The pretest pro!a!ilit$ of +A& is 026" so we consider 022 patients undergoing CTC 02 with +A& and 52 without =f the 02 with +A&" 0 will test negative (sensitivit$ G 526)% of the 52 without +A&" all 52 will test negative (perfect specificit$ G 0226) The post#test pro!a!ilit$ of +A& following a negative CT is 0J50 This is now our pretest pro!a!ilit$ for the U:" so we consider 5022 patients" 022 with +A& and 5222 without =f Correct answer

the 022 with +A&" 0 will test negative (sensitivit$ G 556)% of the 5222 without +A&" all 5222 will test negative (perfect specificit$ G 0226) Therefore" the post#test pro!a!ilit$ of +A& following a negative result in !oth tests is 0J5220 :8-A study is being planned to investigate any lin# between environmental e/posure to pesti ides and new ases of an er. Which of the following stud$ designs is most appropriate? Case- ontrol study Case series Cohort study Cross-se tional survey "andomised ontrolled trial A randomised controlled trial is usuall$ considered the gold standard stud$ design" however it is not suita!le here as it would !e neither practical nor ethical to randomise su!7ects to exposure to pesticides A case series would consist of a num!er of patients with cancer who have a past histor$ of exposure to pesticides While this ma$ !e suggestive of a lin'" it is a ver$ low level of evidence A cross#sectional surve$ would evaluate the prevalence of cancer rather than the incidence A cohort stud$ could answer the stud$ ,uestion !$ following up an entire population over time" measuring exposure to pesticides and o!serving for an outcome of cancer This design is" however" li'el$ to !e prohi!itivel$ expensive A case#control stud$" the past histor$ of pesticide exposure in a group of patients with cancer (cases)" would !e compared to that of a group of patients without cancer (controls) This would ena!le us to answer the stud$ ,uestion !ut avoids the need for long and expensive follow#up re,uired for a cohort stud$ A study is designed to assess the safety of re ombinant human erythropoietin 2rh%PO3 when used in premature infants of less than 88 wee#s gestation to redu e postnatal haemoglobin de line. Out of 81 infants given the treatment none suffered serious side-effe ts. 3/#What should !e concluded from this stud$? rh%PO is safe rh%PO is safe when used in dosages used in this study $othing on lusive an be said, a larger study is needed rh%PO does not ause serious side-effe ts when used in moderate doses Premature infants of less than 88 wee#s gestation an safely be given rh%PO 4ecause 2J-0 have serious side#effects does not mean that no infants ever will" so the drug has not !een shown to !e safe (A" 4" 9 and 8 are incorrect) Correct answer Correct answer

.f -6 of infants were to have serious side#effects from ta'ing the drug" then we would onl$ expect to get 0 in a sample of -2 and it would not !e that surprising to get none A larger stud$ needs to !e done to tr$ and get a more precise estimate of the percentage who will suffer serious side#effects hopefull$ discounting larger percentages About ,* of the 9O population have diabetes.D 31#Which of the following statistical concepts is !eing descri!ed here? In iden e >ifetime ris# 1ortality Prevalen e "elative ris# :revalence descri!es the num!er of cases existing at a time#point compared with the incidence" which is the num!er of new cases occurring during a particular period Uifetime ris' is the pro!a!ilit$ of experiencing a particular condition at an$ time during ones life < for a given individual this ma$ depend on one or more ris' factors @ortalit$ is the rate of deaths < and deaths among those with dia!etes have not !een mentioned Relative ris' descri!es the ris' for one group compared to another" for example the ris' of dia!etes in men compared to women ::-In a study of the re urren e of olore tal adenomas, )' patients were randomised to re eive daily aspirin and )' to re eive pla ebo. After 1 year, at least one adenoma was observed in 1) patients re eiving aspirin and ,' patients re eiving pla ebo. What was the relative ris' reduction associated with aspirin? 1'* ,)* 8'* ;'* 0)* .n the group of 12 patients receiving aspirin there were 01 recurrences" so the ris' of recurrence in these patients was -26 .n the group of 12 patients receiving place!o there were (2 recurrences" so the ris' of recurrence in these patients was /26 The a!solute ris' reduction associated with aspirin was therefore 026 (/26 < -26) The relative ris' reduction is the a!solute ris' reduction as a proportion of the ris' in the control patients" that is (16 (026J/26) :0-In a review of the use of inhaled orti osteroids for the treatment of a ute asthma, the published results of a number of randomised ontrolled trials were ombined to produ e a single estimate of the odds ratio for an out ome of hospital admission. Correct answer Correct answer

Which techni,ue is !eing descri!ed here? Cohort analysis Cost-effe tiveness analysis >ife-table analysis 1eta-analysis &urvival analysis The term meta#anal$sis refers to the techni,ue of com!ining the results of multiple studies (usuall$ randomised controlled trials) to produce one single estimate of treatment effect 4$ com!ining man$ studies" greater precision in this estimate can !e achieved than from an$ one stud$ alone Cohort anal$sis relates to following a group of patients (a cohort) over time Cost#effectiveness anal$sis relates the clinical effectiveness of a treatment to its financial cost Uife#ta!le anal$sis and survival anal$sis !oth refer to techni,ues in which patients are followed up until an event occurs (usuall$ death) and the chance of surviving to an$ given point in time is estimated :@-A ase- ontrol study investigating the effe t of #eeping pet birds on the ris# of lung an er enrolled ,'' patients presenting with lung an er and ,1' ontrols who were free of lung an er. Of the ,'' ases, @' reported a history of at least : monthsD e/posure to a pet bird7 of the ,1' ontrols, 0' reported su h an e/posure. What was the odds ratio for the development of lung cancer associated with 'eeping pet !irds in this stud$? 1 @H0 ),H;) :H) ;H8 Correct answer We construct the following ta!leC 8xposed to pet !irds ?es ;o Total Case @' 1,' ,'' Control 0' 1;' ,1' !otal 1)' ,:' ;1' The odds of an event are calculated as the num!er of times that the event occurs divided !$ the num!er of times that the event does not occur The odds ratio for lung cancer in this scenario is the odds of !eing exposed to pet !irds among the cases (I2J0(2 G (J-) divided !$ the odds of !eing exposed to pet !irds among the controls (F2J0/2 G 0J() +o the odds ratio is /J- ((Jdivided !$ 0J() .t is important to remem!er that as this is a Correct answer

case#control stud$" we cannot calculate the relative ris' (the ris' of !eing a case if exposed divided !$ the ris' of !eing a case if not exposed) The odds ratio is an approximation to the relative ris' if the event is rare A randomised ontrolled trial omparing a new drug for seasonal rhinitis to urrent best treatment uses an e5uivalen e design, on luding that the two treatments are e5uivalent. 35#Which of the following statements !est descri!es the results of the trial? !he ()* onfiden e interval for the treatment effe t fell entirely Correct within prespe ified limits answer !he design of the study was inappropriate as neither treatment was ompared to pla ebo !he out omes in the two arms of the trial were identi al !he results of the study were in on lusive, indi ating that a larger study needs to be performed !here was no statisti ally signifi ant differen e between the two treatments An e,uivalence design is used to show that two treatments are clinicall$ e,uivalent" and will often !e used when a new treatment is considered to !e cheaper or simpler than the esta!lished one < !ut not necessaril$ more effective 8,uivalence limits are set !efore the trial and e,uivalence is esta!lished if we can !e 516 confident that the true treatment effect lies within these limits )or example" if the treatments are !eing compared with a relative ris'" we ma$ set e,uivalence limits of 2 5 and 0 0" indicating that a difference of up to 026 is considered to !e e,uivalent .t is possi!le that one treatment ma$ !e (statisticall$) significantl$ !etter than the other while still !eing clinicall$ e,uivalent" for example if the 516 confidence interval was 0 20 to 0 2I with the e,uivalence limits given earlier As one of the two treatments is esta!lished (and presuma!l$ proven to !e efficacious) it is not necessar$ to include a place!o arm in the trial 0'-A study reports that in a ertain $L& !rust the median door-to-needle time for re eiving thrombolysis following myo ardial infar tion was ,0 minutes, with a lower 5uartile of 1@ minutes and an upper 5uartile of 88 minutes. !he $ational &ervi e Bramewor# target is that 0)* of eligible patients should re eive thrombolysis within 8' minutes of hospital admission. Which of the following statements !est descri!es whether this Trust is meeting the target? Qes, be ause the lower 5uartile is less than 8' minutes Qes, be ause the median is less than 8' minutes Qes, be ause the upper 5uartile is greater than 8' minutes $o, be ause the median is less than 8' minutes

$o, be ause the upper 5uartile is greater than 8' minutes .n a distri!ution" (16 of values lie !elow the lower ,uartile" (16 !etween the lower ,uartile and the median" (16 !etween the median and the upper ,uartile and the final (16 a!ove the upper ,uartile .n this stud$" the upper ,uartile therefore represents the time within which F16 of patients are receiving throm!ol$sis .f the target is !eing met and F16 of patients receive throm!ol$sis within -2 minutes of admission" then the upper ,uartile must !e !elow -2 minutes As the upper ,uartile is greater than -2 minutes" the target is not !eing met

Correct answer

0@-In a study of the effe t of annabinoids in redu ing pain in multiple s lerosis, parti ipants were as#ed to rate their level of pain on a s ale of ' 2no pain3 to 1' 2worst pain imaginable3. Which of the following statements is correct? !he pain s ale is a ontinuous measurement !he pain s ale is an interval measurement !he pain s ale is a nominal measurement !he pain s ale is an ordinal measurement $one of the above An ordinal measurement consists of a num!er of categories that have a natural order !ut the actual values are meaningless .f a patient gives a score of (" then their pain is worse than if the$ had given a score of 0 &owever" the difference !etween a score of 0 and ( ma$ not !e the same as !etween a score of ( and - (the order is meaningful !ut not the value) A nominal measurement has no natural order (eg maleJfemale)" a continuous measurement has meaningful values (eg age) and an interval measurement is the result of dividing a continuous measurement into groups (eg age groups) 0(-In an audit of renal biopsies, there were 10 ompli ations in ); biopsies performed by onsultants 281*3 and : ompli ations in ;( biopsies performed by registrars 21,*3. !he ompli ation rates are ompared using a Chi-s5uared test, reported as C4 , . ).), p . '.',D. &ow should these results !e interpreted? In a given biopsy in the future, a ompli ation is signifi antly more li#ely to o ur if it is performed by a onsultant In a given biopsy in the future, a ompli ation is signifi antly more li#ely to o ur if it is performed by a registrar =e annot draw any on lusion on ompli ation rates in future biopsies as onsultants may have performed more diffi ult biopsies in Correct answer

Correct answer

the audit =e annot draw any on lusion on ompli ation rates in future biopsies as no information has been given regarding the nature of the ompli ations =e annot draw any on lusion on ompli ation rates in future biopsies as the numbers are too small Although the complication rate for consultants in the audit was significantl$ higher than for registrars (p G 2 2()" this ma$ have !een due to the consultants performing more technicall$ difficult procedures This is an example of selection !ias" which can !e a ma7or pro!lem in statistical anal$sis of audit data To remove such a !ias completel$ it is necessar$ to randomise patients to either consultant or registrar +ome attempt to remove the !ias could !e made !$ ad7usting for factors that are 'nown to !e associated with a higher ris' of complications @'-In an "C!, 1''' patients were randomised to re eive either an a tive drug or a pla ebo. Of the )'' randomised to pla ebo, ,' re eived the a tive drug. Of the )'' randomised to the a tive drug, 1' did not re eive the treatment. !he results are to be analysed on an Cintention to treatD basis. What is the final sample si*e in each arm in the anal$sis? )1' treatment, ;(' pla ebo )1' treatment, ;@' pla ebo )'' treatment, )'' pla ebo ;(' treatment, )'' pla ebo ;(' treatment, ;@' pla ebo .n an intention to treat anal$sis" all patients are allocated to treatment groups as randomised" regardless of what treatment the$ actuall$ received 4oth crossovers (patients receiving the treatment the$ were not allocated) and drop#outs (patients receiving no treatment) are anal$sed as if the$ had received their allocated treatment < the$ are neither excluded from the anal$sis nor anal$sed in the arm corresponding to the treatment the$ received .n this wa$" the anal$sis assesses the effectiveness of treating patients with the new drug as opposed to the efficac$ of the drug itself I0#.f screening for !reast cancer !$ mammograph$ has a sensitivit$ of F16 and a specificit$ of 516 in a certain population" what is the positive predictive value? 1H1: )H,; 1(H,; 1)H1: !here is not enough information to al ulate the positive predi tive value Correct answer Correct answer

.n addition to sensitivit$ and specificit$" the prevalence of the disease in the population is re,uired to calculate positive (or negative) predictive value

:ositive predictive value (::K) is the proportion of those testing positive who actuall$ have the disease ('nown as true positives" T:) The num!er of those testing positive who do ;=T have the disease is thus also ta'en into account (false positives" ):) ::K G T:J(T:H):) :ositive predictive value can !e calculated directl$ from the sensitivit$ (A) and specificit$ (4) of the diagnostic test" and the prevalence of the disease in the population (p) asC ::K G A M pJS(0<4) M (0<p)T Bsing the same notation" negative predictive value (;:K) is calculated asC ;:K G 4 M (0<p)JS(0<A) M pT Thus in the example given" without 'nowing the prevalence of !reast cancer in the population !eing tested (and without 'nowing the num!er of true positive and false positive test results)" we cannot calculate the positive predictive value here A study is investigating the relationship between body mass inde/ and systoli blood pressure in a group of individuals. I(#Which of the following graphical methods would !est illustrate the results? 6ar hart 6o/ and whis#er plot Listogram Pie hart & atter plot Correct answer .n a scatter plot" two continuous varia!les are plotted against one another A scatter plot of s$stolic !lood pressure against !od$ mass index (4@.) would therefore show an$ relationship !etween the two A !ar chart could !e used to show the mean s$stolic !lood pressure in different 4@. groups (for example" 4@. E (1" 4@. (1<(5 and 4@. -2) A !ox and whis'er plot or a num!er of histograms could !e used to compare the distri!ution of s$stolic !lood pressure !etween such groups &owever" an$ plot that involved grouping one of the varia!les would lose some information A pie chart is used to illustrate percentages" and would !e of little use here In a study of hypertension, systoli blood pressure measurements are found to be appro/imately normally distributed with a mean 1)' mmLg and varian e 1''. I-#Which of the following statements is correct? Appro/imately ()* of measurements in this population lie between Correct 18' and 10' mmLg answer

Lalf of the patients had a systoli blood pressure below 1'' mmLg !he differen e between the highest and lowest measurements was 1'' mmLg !he distribution of blood pressure measurements is s#ewed =e an be ()* onfident that the mean of the population lies between 1;@ and 1), mmLg This ,uestion tests $our understanding of normal distri!ution and variance The distri!ution is approximatel$ normal" so it is not s'ewed .n a normal distri!ution the median e,uals the mean so approximatel$ half the patients had a measurement !elow 012 mm&g The difference !etween the highest and lowest measurements is called the range We have no information a!out the range" and so option C is incorrect Kariance is the standard deviation s,uared" so a variance of 022 means the standard deviation is 02 mm&g A confidence interval for the mean is calculated from the standard error" which is the standard deviation divided !$ the s,uare root of the sample si*e" ie +8 G +9Js,rt(n) We do not 'now the sample si*e so we cannot compute a confidence interval .n a normal distri!ution" approximatel$ 516 of measurements lie within ( standard deviations of the mean" ie !etween 0-2 and 0F2 mm&g in this scenario @;-Cholesterol is measured in populations from 6ritain, Binland, Tapan and the 9&A, and the four groups are ompared using a one-way analysis of varian e 2anova3. Which of the following graphical methods could !est !e used to illustrate the results? 6ar graph showing the mean holesterol level of ea h group 6o/ plot showing the median, 5uartiles and range for ea h group Bour histograms showing the distribution of holesterol within ea h group Plot of the mean holesterol level with a ()* onfiden e interval Correct for ea h group answer & atter plot of holesterol level against group A scatter plot is used to illustrate the relationship !etween two continuous varia!les% one of the varia!les here is not continuous (group) and so a scatter plot is not suita!le 4ox plots and histograms show the distri!ution of a continuous varia!le These would !e useful for chec'ing the assumption that the distri!ution within each group is approximatel$ normal" !ut are less useful for illustrating the results of the anova The one#wa$ anova compares the means of the groups" so displa$ing the means is the !est wa$ to illustrate the results The means should !e presented with confidence intervals to give the reader an idea of whether the differences !etween the groups were significant @)-!he annual numbers of reported ases of leptospirosis in the 9&A over the 1'-year period from 1(@) to 1((; wereA )0, ;1, ;8, );, (8, 00, )@, );, )1, 8@. What was the mean" median and modal num!er of cases per $ear? 1ean . );, median . );, mode . );

1ean . );, median . @), mode . (8 1ean . ):.:, median . );, mode . ); 1ean . ):.:, median . );, mode . (8 1ean . ):.:, median . @), mode . (8 The mean here is found !$ summing all the values and dividing !$ 02% this gives a mean G 13 3 )or the median and mode" it will help to rewrite the values in ascending orderC ie -I" /0" /-" 10" 1/" 1/" 1F" 1I" FF" 5- The median is the middle value when the values are placed in order )or an even num!er of values it is halfwa$ !etween the two middle values" although in this case that is irrelevant as !oth middle values are 1/ .f $ou forgot to sort the values !efore loo'ing for the middle value" $ou will have got the incorrect answer I1 The mode is the most common value This is 1/" which occurs twice" whereas all other values occur onl$ once The maximum value is 5-% this is not the mode E J+TR=;A D I3#.n a stud$ the odds of disease in the group who smo'e is 2 (1 This means which one of the followingC &mo#ing auses disease Bor every ; who smo#e, 1 has the disease Bor every ) who smo#e, 1 has the disease !he disease o urs ; times more often in those who smo#e A larger sample is needed !he odds in a given group 2in this ase smo#ers3 is defined as the number with diseaseHnumber without disease. =dds in this example are given as 2 (1 G 0J/ i e 0 smo'er with the diseaseJ/ without disease Adding together the num!er of smo'ers with (0) and without disease (/)" the total group can !e considered to !e 0 H / G 1 smo'ers Therefore for 1 smo'ers" 0 has the disease and C is correct @0-A study of hospital admissions reports a produ t moment orrelation oeffi ient between age and length of hospital stay of " . '.0: with a ()* onfiden e interval of '.:0+'.@). &ow should these results !e interpreted? Inade5uate provision of nursing homes prevents the dis harge of older patients Older age was signifi antly asso iated with a longer length of stay Older patients are si #er and re5uire longer stays in hospital Older patients die more 5ui #ly leading to shorter hospital stays !here was no signifi ant relationship between age and length of stay A product moment correlation coefficient greater than *ero indicates a positive association" so older age is associated with longer sta$s As the Correct answer Correct answer

Correct answer

confidence interval excludes the value *ero" this association is significant 8ither A or C ma$ !e true" !ut we do not have enough information to !e a!le to reach these conclusions @@-In a trial of a new an er drug, the mortality in the ontrol arm was 1,.)* and the relative ris# for patients re eiving the new treatment was '.@. &ow man$ patients must !e treated with the new drug to save one life? @ 1' ,) ;' @' The mortalit$ in the experimental arm was 2 I M 0( 16 G 026" so the a!solute ris' reduction is ( 16 (0( 16 < 026) or 0 in /2 +o /2 patients must !e treated to save one life% this is called the num!er needed to treat To confirm this" if /2 patients were treated with the control treatment we would expect 1 deaths (0( 16)" !ut if /2 patients were treated with the new treatment we would expect / deaths (026) @(-A study is being planned to investigate the effi a y of antibioti s to redu e urinary atheter-asso iated sepsis in elderly male patients who are at ris# of pressure sores. What stud$ design is most appropriate? Double-blind, pla ebo- ontrolled, randomised ontrolled trial 2"C!3 Open-label, "C! omparing antibioti s with no antibioti s Prospe tive audit of antibioti use and patient out omes "etrospe tive audit of patient notes 9nblinded, pragmati "C! omparing the use of antibioti s in all patients with the usual pra ti e An audit" whether prospective or retrospective" would !e confounded !$ the li'elihood that anti!iotics will !e given to patients who are considered to !e at higher ris' of sepsis Randomisation is necessar$ to remove this association A pragmatic design would evaluate the effectiveness of introducing a protocol for giving anti!iotics to this patient group &owever" it would not evaluate the efficac$ of anti!iotics as some patients in the control arm ma$ !e given anti!iotics as usual practice To evaluate efficac$" anti!iotics must !e compared to no anti!iotics The least !iased method is to use a place!o for the control arm in a dou!le#!lind trial ('-An study of patients re eiving peritoneal dialysis 2PD3 as renal repla ement therapy is arried out to test the hypothesis that an in reasing number of episodes of PD-asso iated peritonitis is asso iated with de reased time to failure of the peritoneal membrane. Which of the following procedures is appropriate for anal$sing the results? Correct answer Correct answer

B-test Orus#al+=allis test One-sample t-test One-way analysis of varian e 2A$OKA3 &pearmanDs ran# orrelation Correct answer The one#sample t#test compares the mean of a sample to a prespecified value" while the )#test compares the variances of two independent samples < neither is appropriate for this situation 8ither A;=KA or the non#parametric alternative of the Rrus'al<Wallis test could !e used to test the h$pothesis that the time to failure is different among patients with different num!ers of episodes of :9 peritonitis &owever" +pearmans ran' correlation tests for an association !etween the num!er of episodes of :9 peritonitis and the ran' order of the failure times A significant negative correlation would indicate that an increasing num!er of episodes is associated with decreasing failure time A randomised ontrolled trial ompared re urren e rates for patients re eiving a new drug ompared to the standard treatment. !he relative ris# of re urren e for the e/perimental group ompared to the ontrol group was '.( with a ()* onfiden e interval of '.0+1.1. 50#&ow should these results !e interpreted? "e urren e rates with the new drug were onsistent 2with ()* onfiden e3 with anywhere between a 8'* de rease and a 1'* in rease ompared to the standard treatment "e urren e was signifi antly higher 2at the )* level3 in patients re eiving the new drug ompared to the standard treatment "e urren e was signifi antly lower 2at the )* level3 in patients re eiving the new drug ompared to the standard treatment !he differen e between the treatments was too small to be of any lini al importan e !here was no differen e between the treatments Correct answer

The confidence interval for the relative ris' includes the num!er 0" so the trial did not find a statisticall$ significant difference !etween the treatments &owever" 7ust !ecause the difference was not significant this does not mean there was no difference We have not !een given enough information to !e a!le to ma'e a value 7udgement a!out whether this difference is clinicall$ significant +tatistical insignificance does not necessaril$ impl$ clinical insignificance (,-A patient is admitted with a suspe ted DK!. !he patient has a high lini al s ore giving a pretest probability for DK! of ,H) 2;'*3. .f a clinical test has a sensitivit$ of 526 and a specificit$ of I26 to detect 9KT" what is the post#test pro!a!ilit$ for this patient if the test is negative? 1H,) 1H1)

1H18 1H1, @H,)

Correct answer

+uppose we have 12 patients with a pretest pro!a!ilit$ of (J1 =n average" (2 of these will have a 9KT =f the (2 with a 9KT" 0I will test positive (sensitivit$ G 526) =f the -2 without a 9KT" (/ will test negative (specificit$ G I26) We construct the following ta!leC 9K ;o T 9KT Test positive Test negative Total 0I 3 ( (/ Tot al (/ (3 12

(2 -2

The post#test pro!a!ilit$ given a negative test result is the proportion of patients who tested negative !ut actuall$ have a 9KT This is (J(3 or 0J0Alternativel$" $ou could reach this answer !$ converting the pretest pro!a!ilit$ to the pretest odds (odds G pro!a!ilit$J(0 < pro!a!ilit$))" multipl$ing !$ the li'elihood ratio for a negative for a negative result (UR<) to o!tain the post#test odds" and converting this !ac' to the post#test pro!a!ilit$ The other answers could !e o!tained (incorrectl$) !$C multipl$ing the pretest pro!a!ilit$ !$ 0 < sensitivit$ (option A)% multipl$ing the pretest pro!a!ilit$ !$ UR< (option 4)% failing to convert the post#test odds to the pro!a!ilit$ scale (option 9)% and multipl$ing the pretest pro!a!ilit$ !$ the specificit$ (option 8) (8-A new s reening test is to be applied in a population. !he test has a sensitivity of ((* and a spe ifi ity of ('*. .f the prevalence of the disease is 02 per 0222 population" on average what proportion of those that test positive will trul$ have the disease? 1H11 1H1' 1H, (H1' ((H1'( +uppose that 02"222 people are tested" the prevalence of the disease is 06 (02 per 0222) so 022 of these will have the disease and 5522 will not =f the 022 with the disease" 55 will test positive (sensitivit$ G 556)" and of the 5522 without the disease" 552 will test positive (specificit$ G 526) We can now construct the ta!le !elowC E J+TR=;A D 9isea se Correct answer

?es Test positive Test negative Total 55 0 022

;o

Tota l

552 02I5 I50 I500 2 552 0222 2 2

The proportion of those that test positive who trul$ have the disease is 55J (55 H 552) G 0J00 This is the positive predictive value E J+TR=;A D Clini ally obese patients are randomised to re eive either intensive dieti ian follow-up or normal treatment. 5/#Which of the following tests is appropriate to test whether the mean weight loss is different !etween the two groups? Analysis of varian e B-test Independent samplesD t-test Paired samplesD t-test U-test An )#test is used to compare the variances of two groups Anal$sis of variance is used to compare the means of more than two groups A V#test is used to compare the means of two groups when the variances of the two groups are 'nown < this is not the case here" so we re,uire a t#test =ur two samples are not paired (as" for example" two measurements on the same group of patients would !e) so we re,uire the independent samples t#test ()-!he average weight of a group of 1'' patients is :' #g, standard deviation ) #g. =eights are normally distributed. The standard error of the weights is which one of the following? 1, #g '.: #g ) #g >arger than the standard deviation &maller than the standard deviation Correct answer Correct answer

+tandard error G standard deviation J the s,uare root of n (022 in this case" hence 8 is correct (:-In a sample of :; patients admitted to an intensive are unit, the mean APACL% II illness severity s ore was 1; with varian e 1:. Which of the following is an approximate 516 confidence interval for the mean score?

: to ,, 1' to 1@ 18 to 1) 18.) to 1;.) 18.0) to 1;.,) An approximate 516 confidence interval for the mean is given !$ the mean twice the standard error The standard error is the standard deviation divided !$ the s,uare root of the sample si*e" and the standard deviation is the s,uare root of the variance +o we haveC +tandard deviation G 03 G / +tandard error G /J 3/ G /JI G W 516 confidence interval G 0/ (( M W) G 0- to 01 In a randomised ontrolled trial of a new treatment for preventing re urren e of stro#e, 1''' patients are randomised to the new treatment and 1''' to standard therapy. A total of :: patients re eiving the new treatment suffered re urrent stro#e, ompared to 11' in the ontrol arm. 5F#What was the relative ris' reduction? ;.;* :.:* 11* ;'* :'* The ris' of recurrent stro'e in the treatment arm was 3 36 (33J0222) The ris' of recurrent stro'e in the control arm was 006 (002J0222) The difference in these ris's is the a!solute ris' reduction" / /6 (006 < 3 36) The relative ris' reduction is the a!solute ris' reduction as a percentage of the ris' in the control group" that is /26 (/ /J00) (@-In ,'' onse utive patients attending a diabeti out-patients lini , ,0 are found to have diabeti retinopathy. Which of the following statements is correct? !he in iden e of diabeti retinopathy in diabeti s in the 9O is 18.)* !he in iden e of diabeti retinopathy in this population was 18.)* !he prevalen e of diabeti retinopathy in diabeti s in the 9O is 18.)* !he prevalen e of diabeti retinopathy in this population was 18.)* !his study does not provide any information on the in iden e or prevalen e of diabeti retinopathy The prevalence of a disease is the num!er of cases present in a population at a point in time The incidence of a disease is the num!er of new cases Correct answer Correct answer

Correct answer

over a period of time The figure reported in the ,uestion is the prevalence" and the prevalence in this population was 0- 16 This population ma$ !e representative of all dia!etics in the BR" in which case we could ta'e 0- 16 to !e an estimate of the prevalence in BR dia!etics" although it is li'el$ that some selection has occurred ((-A study see#s to find an asso iation between in reasing per eptions of pain 2ran#ed on a s ale of 1+1'3 and in reasing heart rate. Which of the following measures is most appropriate? Analysis of varian e Chi-s5uared test PearsonDs orrelation oeffi ient Produ t moment orrelation oeffi ient &pearmanDs ran# orrelation oeffi ient Correct answer

The Chi#s,uared test is used to test for independence !etween two categorical varia!les Anal$sis of variance tests for a difference in mean values !etween a num!er of groups .t would tell us if the mean heart rate is different for different pain ran'ings" !ut not whether increasing pain is associated with increasing heart rate :earsons correlation coefficient and the product moment correlation coefficient are two names for the same thing (often called R) R is a measure of association !etween two continuous scale measurements The measure of pain is not on a continuous scale" so options C and 9 are not the !est measure +pearmans ran' correlation coefficient measures the correlation !etween the ran's of two varia!les As it onl$ compares ran's and not values" it is appropriate for use on an ordered categorical (ordinal) varia!le such as the perception of pain 1''-6lood pressure is normally distributed. Bor a sample of 1'' Asian women the average blood pressure is )', standard deviation . ), standard error . 1H,. Which one of the following statements is correct? Appro/imately ()* of Asian women have blood pressures in the range 2;),))3 =e are appro/imately ()* onfident that the population average blood pressure for Asian women lies in the interval 2;(, )13 6lood pressure measurement in Asian women is not informative 1'* of Asian women have blood pressure below ;' mmLg !he mean blood pressure of Asian women must lie within the range 2;(, )13 Approximatel$ 516 will have !lood pressures in the range (mean O (sd) G (12 O ((1)) G (12 O 02) G (/2" 32) so A is incorrect ( 16 will have !lood pressures !elow /2 (9 is incorrect) A 516 confidence interval for average !lood pressure is given !$ (mean O (se) G (12 O ((0J() G 12 O 0 G (/5"10)" so 4 is correct (Although we are 516 confident that the mean lies in this range it ma$ not and 8 is incorrect )

Correct answer

1'1-A study measures the redu tion in Lb A1 in patients with type-, diabetes randomised to re eive either a new drug or standard therapy. Which of the following tests is most appropriate to test the h$pothesis that the mean &! A0c reduction is different in the two groups? 1ann+=hitney 9-test 1 $emarDs test Paired t-test 9npaired t-test =il o/on signed-ran# test @c;emars test is used to compare proportions The @ann<Whitne$ B#test and Wilcoxon signed#ran' test are non#parametric tests" and so compare the overall distri!utions rather than the mean values 4oth the t#tests compare means !etween two groups% however" in our case the two groups are independent groups of patients so the$ are not paired 1',-In an audit of hospital episode statisti s, length of hospital stay for a ute medi al admissions is found to be highly positively s#ewed with a median of ; days and an inter5uartile range of ,+1' days. Which of the following statements is correct? ,)* of patients stayed between , and 1' days )'* of patients stayed between , and 1' days ('* of patients stayed between , and 1' days ()* of patients stayed between , and 1' days All patients stayed between , and 1' days The lower ,uartile has one#,uarter of values !elow it" and the upper ,uartile has one#,uarter of values a!ove it The inter,uartile range" (<02" is the range from the lower ,uartile to the upper ,uartile" so half of all values lie in this range 02-#Which one of the following statements concerning the distri!ution curve is accurate? !he mode is the sum of all the s ores divided by the number of s ores !he mean is a good measure of entral tenden y in s#ewed distributions !he mean is higher than the median in positively s#ewed Correct distributions answer =hen there is an even number of numbers, the mode is the mean of the two middle numbers In any given distributions there is only one mode The mean is a good measure of central tendenc$ for roughl$ s$mmetric distri!utions !ut can !e misleading in s'ewed distri!utions since it can !e greatl$ influenced !$ extreme scores Therefore" other statistics such as the Correct answer Correct answer

median ma$ !e more informative for distri!utions such as reaction time or famil$ income that are fre,uentl$ ver$ s'ewed )or normal distri!utions" the mean is the most efficient and therefore the least su!7ect to sample fluctuations of all measures of central tendenc$ The median is the middle of a distri!ution (half the scores are a!oce the median and half are !elow the median) The median is less sensitive to extreme scores than the mean and this ma'es it a !etter measure than the mean for highl$ s'ewed distri!utions The median income is usuall$ more informative than the mean income" for example" when there is an odd num!er of num!ers" the median is simpl$ the middle num!er when the num!ers are arranged on order of magnitude )or example" the median of ("/" and F is / When there is an even num!er of num!ers" the median is the mean of the two middle num!ers Thus" the median of the num!ers ("/"F"0( is (/HF)J(G 11 The mean" median" and mode are e,ual in s$mmetric distri!utions The mean is higher than the median in positivel$ s'ewed distri!utions and lower than the median in negativel$ s'ewed distri!utions The mode is the most fre,uentl$ occurring score in a distri!ution and is used as a measure of central tendenc$ The advantage of the mode as a measure of central tendenc$ is that its meaning is o!vious )urther" it is the onl$ measure of central tendenc$ that can !e used with nominal data The mode is greatl$ su!7ect to sample fluctuations and is therefore not recommended to !e used as the onl$ measure of central tendenc$ A further disadvantage of the mode is that man$ distri!utions have more than one mode These distri!utions are called Qmultimodal Q 1';-Admissions to a medi al admissions unit were audited for a period of 1 wee#. Bor ,,) admissions, the mean length of time to see a do tor was ,.) hours 2standard deviation 1.) h3, and the median time to see a do tor was 1.) h. Which of the following statements is correct? A ()* onfiden e interval for the mean time to see a do tor is ,.;+,.: h Lalf of all patients waited at least ,.) h to see a do tor ()* of patients were seen by a do tor within ).) h !he distribution of the time to see a do tor was appro/imately normal !he distribution of the time to see a do tor was positively s#ewed

Correct answer

.n a normal distri!ution" the mean and median are e,ual" so these data are not normall$ distri!uted As the data are not normall$ distri!uted" we cannot assume that 516 of values lie within two standard deviations of the mean Although the distri!ution of waiting times is not normal" the distri!ution of the mean will still !e approximatel$ normal (this is called the central limit theorem) The standard error of the mean is 2 0" so a 516

confidence interval for the mean wait is ( -<( F h As the median wait was 0 1 hours" half of all patients waited at least 0 1 h As the mean is greater than the median" this indicates a positive s'ew 1')-A new smo#ing- essation therapy is found to in rease 5uality-ad-usted life years 2VA>Qs3 ompared to standard therapy by an average of 1., VA>Qs at a ost of W8),''' per VA>Q gained. Which of the following conclusions can !e drawn from this information? An additional 1., lives per year ould be saved if the government invested W8),''' in funding this therapy Patients re eiving the new therapy lived an average of 1., years longer than those who did not !he new therapy improved smo#ersD 5uality of life !he new therapy is ost-effe tive !o de ide whether the new therapy is ost-effe tive re5uires a value Correct -udgement answer XAU?s ta'e account of !oth the ,ualit$ of life and the length of life The smo'ers who received the new therap$ ma$ either have lived longer or had an improved ,ualit$ of life or some com!ination of these" !ut we are una!le to determine which from the information presented The total cost of funding this intervention also cannot !e determined" as we would need to 'now how man$ patients would !e eligi!le to receive the new therap$ and at what cost We do 'now that ever$ Y-1"222 will improve outcomes !$ one XAU? Whether this is an appropriate use of mone$ re,uires a value 7udgement" as there is onl$ a finite amount of mone$ availa!le and it ma$ !e !etter spent on other interventions =nl$ if it is decided that Y-1"222 per XAU? is an accepta!le cost could we conclude that the therap$ is cost# effective .t has !een suggested that ;.C8 use a threshold of Y-2"222 per XAU? to determine cost#effectiveness% however" the new therap$ would not !e considered cost#effective with this cut#off 1':-A study is underta#en to investigate the impa t of simple hygiene measures on the rates of 1"&A ontamination of do torsD tourni5uets. A random sample of tourni5uets is swabbed before the intervention, and a se ond random sample is tested after the intervention. !he results are presented in a ,S, ontingen y table, and the redu tion in 1"&A ontamination rates is tested with a Chi-s5uared test. !he result of the Chi-s5uared test is reported as CC, . ;.@, p . '.'8D. =hat does Cp . '.'8D meanX 8* of do torsD tourni5uets are ontaminated with 1"&A If the e/periment were to be repeated 1'' times, this result would be found at least 8 times !he probability that a differen e of this magnitude would have Correct o urred by han e is 8* answer !he probability that this intervention has redu ed the ontamination rate is 8* !he rate of ontamination has been redu ed by 8*

The statement p G 2 2- is reporting the p#value of the test .t does not represent the contamination rate or the reduction in contamination The p# value represents the pro!a!ilit$ that a result of e,ual or greater magnitude to the actual result of the stud$ would have occurred !$ chance if the intervention had no effect This could !e interpreted as meaning that the pro!a!ilit$ that the intervention has trul$ reduced the contamination rate is 5F6 .f the experiment were to !e repeated 022 times and the intervention has no effect" then we would expect a result of this si*e to occur on average - times 1'0-A group of patients have their albumin levels measured at hospital admission and again 8 wee#s into their hospital stay. Which one of the following statistical tests is most appropriate to test the h$pothesis that the al!umin levels have changed? Chi-s5uared test Independent samples t-test >inear regression One-way analysis of varian e Paired samples t-test Correct answer

4ecause we re,uire a test that compares two groups (al!umin level at admission and al!umin level after - wee's)% anal$sis of variance is not appropriate as it compares more than two groups The outcome measurement is continuous rather than categorical" so the Chi#s,uared test could not !e used without first dividing the al!umin measurements into ar!itrar$ categories As !oth sets of measurements were made on the same patients" the measurements are not independent Although linear regression could !e used to model the relationship !etween the initial and final measurements" to test for a change in the mean al!umin levels" the correct test is the paired samples t#test 1'@-A study is planned into the effe ts on ris# of myo ardial infar tion of a new lipid modifying agent, and the steering ommittee states that they plan to in lude number needed to treat 2$$!3 as part of the primary manus ript. &ow is the num!er needed to treat over the duration of the stud$ calculated? "atio of absolute to relative ris# redu tion "atio of relative to absolute ris# redu tion "e ipro al of relative ris# redu tion "e ipro al of absolute ris# redu tion $umber of months of study divided by the absolute ris# redu tion The ;;T is the num!er of patients re,uired to !e treated over the duration of the stud$ to save one of the event referenced" e g m$ocardial infarction )or safet$ events" for example !leeding after administration of ..!J...a Correct answer

inhi!itors a num!er needed to harm is calculated 4alancing the num!er needed to treat versus the num!er needed to harm ena!les an assessment of true clinical effectiveness 1'(-A study in patients aged 0) and over measures the effe tiveness of warfarin versus aspirin with regards to redu tion of emboli stro#e. After the study has losed the group treated with warfarin have a 1.,* ris# of emboli stro#e over the period of the trial, whereas those on aspirin have a ,.;* ris#. What is the a!solute ris' reduction for warfarin versus aspirin in this stud$? )'* ,'* 1.,* ,.;* 8.:* The a!solute ris' reduction is calculated !$ calculating ( /#0 (6G0 (6 The relative ris' reduction is 126 (calculated asC (( /#0 ()J( /) The a!solute stro'e ris' on warfarin is also 0 (6 over the duration of this trial A num!er needed to treat for warfarin as an alternative to aspirin can !e calculated as the reciprocal of the a!solute ris' reduction" in other words" 0J2 20( 002#?ou are drawing up a trial of a new screening test .f the threshold of the screening test is increased" which of the following would increase? &ensitivity &pe ifi ity Prevalen e $egative predi tive value Positive predi tive value .f the definition of a positive screen result is altered !$ an increase in threshold" then the prevalence of the disease as defined !$ the positive screening test will increase The positive predictive value is the proportion of patients with a positive test result are correctl$ identified" correspondingl$ the negative predictive value is the proportion of patients with a negative test result who are correctl$ identified The sensitivit$ of a test is the percentage chance of recognising all people with the disease" specificit$ the chances of a positive test onl$ identif$ing patients with a particular condition 111-A letter published in a -ournal suggests an established antidepressant may ause photosensitivity. !he manufa turer wishes to determine as rapidly as possible whether this a true asso iation. Which one of following techni,ues is most appropriate? Case- ontrol study Dose-ranging study Correct answer Correct answer

Double-blind, randomised, pla ebo- ontrolled study 1eta-analysis &e5uential trial @eta#anal$sis of the availa!le pu!lished clinical trials is the most effective wa$ to determine if there was a true association !etween an anti# depressant and photosensitivit$ This necessitates the examination of safet$ data and reported adverse events of rash or photosensitivit$ !etween place!o and active comparator arms of clinical studies .t is li'el$ that even the place!o stud$ arms report a !ac'ground rate of photosensitivit$" so the results are li'el$ to !e given as percentage differences !etween the two groups rather than as a $es#or#no result Case# control stud$ esta!lishes epidemiological association" !ut does not esta!lish causalit$ Also" safet$ data is often fraught with inaccuracies" and the imperfect reporting of adverse events ma$ even s'ew the results of such a meta#anal$sis 00(#Which of the following most accuratel$ reflects information from post# mar'eting surveillance of 02 222 patients given a new drug? Adverse events profile Cost+benefit analysis Cost-effe tiveness Comparative therapeuti effi a y Drug poten y @edicines are tested for efficac$ and safet$ !efore !eing granted a product licence" !ut on average onl$ (222<-222 patients are used This is due to time and cost constraints .t could ta'e as long as 0( $ears and cost Y/22 million to produce one new drug Aside from financial considerations" there are external pressures to ma'e drugs availa!le as soon as possi!le" especiall$ in life#saving situations :rescri!ing cost containment is another pressure :re#mar'eting trials are artificial in that the drugs are used in well#controlled situations with full compliance to recommended regimens and close monitoring The$ normall$ exclude patients most vulnera!le to adverse reactions such as the frail and elderl$" and those on multiple drug regimens with multiple pathologies &owever" the !iggest pro!lem is trial si*e A patient cohort of -222 will onl$ highlight reactions more fre,uent than 0 in 0222 A!sence of evidence is not evidence of a!sence" and the need for a comprehensive data!ase is therefore high :ost#mar'eting surveillance involves monitoring the safet$ of medicines under their usual conditions of use .t is carried out to identif$ an$ new safet$ concerns (h$pothesis generating)" and to confirm or refute these concerns (h$pothesis testing) 118-A new anti-diabeti agent is laun hed on the 9O mar#et. !here was some on ern in one of the animal studies whi h too# pla e in development that there may be an in reased ris# of ar inoma of the bladder asso iated with its use. Which of the following would !e most useful in determining if there is a ris' of !ladder cancer when the drug is used in a larger population? Correct answer Correct answer

Burther me hanisti studies in another mammalian mode A long-term post-mar#eting randomised ontrolled trial A ohort study A ase ontrol study A database study Cases where rare side#effects of pharmaceutical agents have onl$ !ecome apparent post#launch are common A standard phase - programme containing around -222 patients ma$ reasona!l$ !e expected to onl$ detect an adverse event which occurs with a fre,uenc$ of around 0 per ever$ 0222 patients treated A data!ase stud$ ma$ !e fraught with confounders and a cohort or long#term post#mar'eting RCT would ta'e too long to conduct" hence a case#control stud$ would !e the ideal initial step in investigating a lin' !etween the drug and ris' of !ladder carcinoma 11;-A phase 1 pharma o#ineti study is ondu ted to investigate whether a drugYs plasma on entrations are related to weight. &ub-e ts are given a single dose of the drug and plasma levels are measured , h later. What is the most appropriate statistical test to evaluate the results? Paired t-test Chi-s5uared test 9npaired t-test >og regression analysis PearsonDs orrelation :redicting factors of plasma concentrations are !est anal$sed using the log regression anal$sis Karia!les are entered into a !inar$ logistic regression model to identif$ independent ris' factors 11)-A 08-year-old man is admitted to the hospital after suffering a left arotid territory stro#e. Lis blood pressure is 1))H(' mmLg and he is in sinus rhythm with a pulse of :) bpm. On arotid duple/ it appears there is a stenosis whi h is amenable to surgi al therapy. Le as#s you about the ris#s of surgery versus intensive medi al therapy. On reviewing the trials you note that the in iden e of stro#e in the surgi al intervention group was @*, versus 1@* in those who had medi al intervention only. &ow would $ou calculate the num!er needed to treat over ( $ears with surger$ to prevent 0 stro'e? 1''H21@-@3 1@H@ 1''H21@H@3 1@-@ 1''-21@H@3 +tep 0 is to calculate the difference in a!solute ris' in percentage terms !etween the two treatments" 0I#I gives a difference in a!solute ris' of 026 Correct answer Correct answer Correct answer

or 2 0 To scale it up to give us an ;;T" we divide 022J026" which gives us an ;;T of 02 +o $ou need to treat 02 patients with surger$ to prevent 0 stro'e over the course of ( $ears 11:-In a trial of a new antihistamine drug, an e/tra 1 in every ) patients treated 2()* onfiden e intervalA 1 in 8.8 to 1 in 1'3 were found to have redu ed symptoms two wee#s after ommen ing the drug, ompared to pla ebo. The most correct interpretation of the results of this stud$ isC )* of patients did not have redu ed symptoms after , wee#s on the new drug !he effe t of the new drug is not signifi antly different from pla ebo =e an be ()* ertain that between 1'* and 8'* of patients will Correct benefit from the new drug answer !he Cnumber needed to treatD 2$$!3 statisti presented is inappropriate for this type of study !he statisti al signifi an e of this result annot be determined as no P-value is reported 4oth ends of the 516 confidence indicate a positive effect of the new drug relative to place!o" so the difference is statisticall$ significant < a :#value is not needed when a 516 confidence interval is reported% thus" options 4 and 8 are !oth wrong ;;T is an ideal summar$ statistic for this t$pe of stud$" so option 9 is also wrong We cannot determine the proportion of patients with reduced s$mptoms after two wee's from the information given < so option A is wrong A ratio of 0 in - - is e,uivalent to -26 and a ratio of 0 in 02 is e,uivalent to 026 < so the 516 confidence interval for ;;T can !e re# expressed as (--6 to 026) < !etter expressed as (026 to --6)% option C is correct 110-A ;@-year-old patient with type , diabetes visits you in the lini and has brought with him a printout from the Internet about the Proa tive study. Le is demanding that he be ommen ed on pioglita<one ;) mg as it has a benefit with respe t to ardiovas ular disease. "elative-ris# redu tion for the ombined end-point of death from any ause, non-fatal myo ardial infar tion 2e/ luding silent3 or stro#e was 1:*, absolute-ris# redu tion of ,.1* over 8 years. Which of the following fits !est with the num!ers needed to treat to avoid the com!ined end#point shown a!ove?

@; ;@ : ,.1 , )ort$#eight patients would have to !e treated for a period of - $ears to avoid one death" non#fatal m$ocardial infarction or stro'e ;um!ers needed to treat are calculated !$ dividing 022 !$ the a!solute reduction in events in6age terms This wor's out to !e /I for the proactive stud$ While the Correct answer

glita*ones initiall$ were thought to have significant long#term cardiovascular promise" this stud$ was ultimatel$ seen as disappointing !$ man$ commentators 11@-A new test is developed for the diagnosis of hepatitis C. Out of 1',''' tests 1'' were positive using the urrent gold standard method for diagnosing hepatitis C, whereas using the new method 1)' tests were positive. What is the positive predictive value of the new test? ,)* 8'* ::* 1)'* )'* The positive predictive value of a test G true positiveJ(true positive H false positive) G 022J(022H12) The negative predictive value of a test G true negativeJ(true negative H false negative) 4oth the positive and negative predictive values of a test are important in esta!lishing its value as a screening tool 11(-In a randomised ontrolled trial omparing selenium supplementation with pla ebo in patients with a history of basal- ell or s5uamous- ell ar inomas of the s#in, the primary out ome measure is the in iden e of basal- ell or s5uamous- ell ar inomas at 1 year. Which of the following tests is most appropriate to assess this outcome? Analysis of varian e Chi-s5uared test 1ann+=hitney 9-test 1 $emar test &tudentDs t-test Anal$sis of variance" +tudents t#test and the @ann<Whitne$ B#test are all tests for continuous outcome measures (anal$sis of variance compares the means of multiple groups" +tudents t#test compares the means of two groups and the @ann<Whitne$ B#test is a non#parametric comparison of two distri!utions) The incidence of carcinomas is a !inar$ outcome" so these three tests are not appropriate The @c;emar test compares !inar$ outcomes for two paired groups% the two groups in this RCT are independent so this is not suita!le The appropriate test for this situation is the Chi#s,uared test" which compares independent categorical (including !inar$) outcomes Correct answer Correct answer

1,'-Qou are as#ed to design a trial for a new anti-hypertensive agent after ta#ing part in the phase , studies. Qou suspe t that it has a power to a hieve a relative ris# redu tion of 1@* in CK events. Qou are e/amining methodology and statisti al tests to determine effe tiveness of this agent. What is the power of a statistical test? !he probability that it will orre tly lead to re-e tion of a false null Correct hypothesis answer !he probability that it will falsely lead to re-e tion of a true null hypothesis !he probability that it will falsely lead to re-e tion of a false null hypothesis !he probability that it will orre tly lead to re-e tion of a true null hypothesis !he sample si<e needed to dete t a signifi ant differen e The power of a statistical test is the pro!a!ilit$ that it will correctl$ lead to re7ection of a false null h$pothesis% in other words" that a difference !etween two populations" e g a treated and untreated patient group will !e correctl$ detected Xuite often the null h$pothesis ma$ !e accepted due to insufficient sample si*e" therefore ma'ing sure that $our clinical trial is ade,uatel$ powered to detect a difference !etween populations is cruciall$ important 1,1-Con ern has been e/pressed that people who live near overhead ele tri ity power ables are at in reased ris# of developing a an er. What would !e the !est design for a stud$ to investigate this concern? A group omparative randomised ontrolled trial 2"C!3 A ross-over "C! A retrospe tive ase- ontrol study A prospe tive ohort study An observational survey An "C! is unli#ely to be either ethi al or pra ti al in this onte/t. Options A and 6 both re5uire people to be randomly allo ated to live near or away from overhead power ables + in addition, option 6 re5uires them all to hange their pla e of residen e half-way through the studyZ An observational study 2option %3 would provide some insight + but any differen e in an er rates between the people surveyed who lived lose to and far away from overhead power ables ould be due to other fa tors 2su h as age, length of time resident in area, et 3 that annot be ontrolled for in a simple survey. Option D has onsiderable appeal + ohorts of people living near to and far away from overhead power ables 2mat hed overall for important onfounding hara teristi s3 would be identified and followed up for an appropriate period of time. At the end of the study, the proportions in ea h group who had developed a an er would be ompared. In this onte/t, however, the follow-up period would have to be very long 21' or even ,' years3. A more immediate result is needed. Option C does have it faults, but is the best of the designs offered. =ith this design, re ently diagnosed ases 2patients with a an er3 are identified. %a h ase is then mat hed with one or more ontrol sub-e ts 2people without a an er3 on Correct answer

important onfounding fa tors 2e.g. age, se/, time resident in urrent house, et 3. At the end of the study, the proportions of ases and ontrols living lose to and far away from overhead power ables are ompared. 1,,-A lini al psy hologist arries out a large-s ale study to measure an/iety levels in patients attending a hospital day-surgery unit. !o help with the interpretation of the study findings, he re ruits a group of ontrol sub-e ts from the orthopaedi lini held on the same day ea h wee# as the day-surgery lini . =hen the study has ended, he finds that the ontrols in lude a slightly greater proportion of men and are slightly older on average than the day-surgery patients7 both age and se/ are #nown to influen e the an/iety s ale he used. What would !e the most appropriate method of comparing the anxiet$ levels of the two stud$ groups? A 1ann-=hitney 9-test An unpaired &tudentDs t-test 1ultiple linear regression A series of Pearson orrelation oeffi ients $othing + the an/iety levels annot be ompared as the groups differ with respe t to important onfounders so a new, better designed study is needed Argua!l$" 8 is the correct option here &owever" there are ethical issues associated with throwing awa$ the data from a stud$ after a large num!er of su!7ects have given of their time and efforts to complete the anxiet$ scale .n an$ case" the im!alances on !oth age and sex are descri!ed as !eing onl$ slight The !est option" therefore" is C @ultiple regression (or anal$sis of variance) methods can !e used to (mathematicall$) ad7ust the anxiet$ levels for an$ relationship the$ have with age and sex !efore testing the statistical significance of the difference in mean level !etween the stud$ groups A series of :earson correlations (option 9) might provide some insight into the strengths of the relationships !etween anxiet$ level and each of age and sex" !ut do not provide a complete anal$sis =ptions A and 4 are !oth valid methods for comparing two independent groups !ut do not allow an$ ad7ustment to made for the effects of age and sex 1,8-&hort stature normal hildren are randomised to re eive a new growth hormone or a pla ebo preparation. !he per entage of individuals re ording side-effe ts 2yesHno3 in ea h group is to be ompared. Which statistical test or techni,ue is appropriate for this purpose? Chi-s5uare Correlation analysis 1ann+=hitney 9 test "egression analysis &tudentDs t-test Correct answer Correct answer

The primar$ o!7ective of this stud$ is to compare the proportions in the two (independent) stud$ groups who experienced side#effects The Chi#s,uare test (option A) is the onl$ listed method appropriate for doing this 1,;-A new glu ose test is developed to dete t diabetes. !he test has sensitivity @'* and spe ifi ity ('*. !he positive li#elihood ratio is therefore @'H21'' + ('3 . @. One person in every 10 of those presenting to your lini has diabetes 2i.e. pretest odds . 1H1:3. )or a person who enters $our clinic and then tests positive on the new screening test" their post#test odds of having dia!etes are which of the following? )'* ,)* :.:* @'* ('* Post-test odds . pre-test odds / positive li#elihood ratio . 1H1: / @ . [ or 1 in ,. 9ltrasound s anning at ,' wee#s was found to orre tly dete t 8) of the )' babies ultimately diagnosed as having a ongenital heart defe t. Lowever, five of the )'' babies born with no ongenital defe t were also re orded as problemati when s reened. 0(1#Which of the following is a correct statement of the properties of ultrasound scanning as a screening test for congenital heart defects? Positive predi tive value . 0'*7 negative predi tive value . ((* Positive predi tive value . 0'*7 negative predi tive value . 1* &ensitivity . 0'*7 spe ifi ity . ((* &ensitivity . 0'*7 spe ifi ity . 1* $o test properties an be estimated as these are all affe ted by the prevalen e of ongenital heart defe ts in the study population - this figure is not given Bor a s reeningHdiagnosti testA sensitivity is the proportion of individuals with the disease orre tly diagnosed7 spe ifi ity is the proportion of individuals without the disease orre tly diagnosed7 positive predi tive value is the proportion of individuals with a positive test result found to have the disease7 negative predi tive value is the proportion of individuals with a negative test result found not to have the disease. &ensitivity and spe ifi ity are unaffe ted by the prevalen e of the disease, so an be meaningfully estimated from the results of this study. Positive and predi tive values, however, are dependent on disease prevalen e, so are should be e/er ised when interpreting these. In this study, 8) 20'*3 of the )' babies with a ongenital heart disease were orre tly diagnosed, ma#ing the test sensitivity 0'*. In addition, ) 21*3 of the )'' babies without a defe t were in orre tly diagnosed + so ;() 2((*3 of the CnormalD babies were orre tly diagnosed, ma#ing the test spe ifi ity ((*. Len e, the orre t option is C. Correct answer Correct answer

$oteA In this study, a total of ;' babies s reened positive, of whi h 8) were found to have a defe t, ma#ing the positive predi tive value . 8)H;' . @0.)*. A total of )1' babies s reened negative, of whi h ;() were defe t-free, ma#ing the negative predi tive value . ;()H)1' . (0*. A large-s ale national study into the stature of s hool hildren on ludes that there is a relationship between the heights of siblings, in that tall boys tend to have tall sisters 2r . E'.,0, P F '.'1'3. 0(3#We can conclude from this stud$ thatC ,0* of girls were a tually taller than their brothers !he value of the orrelation oeffi ient is too small to be statisti ally signifi ant - a larger study is needed Leight is geneti ally determined !he sisters of tall boys are very mu h taller than the sisters of short boys !here is a numeri ally small but statisti ally signifi ant relationship between the heights of brothers and sisters

Correct answer

=ption A is total nonsenseZ Correlation coefficients do not translate into percentage statements a!out the relationship !etween su!7ects =ption 4 is incorrect As the :#value for the correlation coefficient is less than 2 21" the relationship is statisticall$ significant at the conventional 16 level < so the fact that the value of r is numericall$ small is irrelevant )urthermore" as a significant relationship has !een esta!lished" there is little to !e gained from conducting a larger stud$ =ption C ma$ well !e correct" !ut it does not follow from the result of this stud$ +tatistical correlation coefficients merel$ estimate the strength of the relationship !etween two measures (in this case" the heights of si!lings) < !ut cause and effect cannot !e inferred =ption 9 ma$ also !e true" !ut we do not have sufficient information to ma'e this inference < we need the regression e,uation for this The relationship could actuall$ !e ,uite modest" with the sisters of tall !o$s onl$ !eing slightl$ taller on average than the sisters of short !o$s =ption 8 is correct # r is indeed numericall$ small" !ut as : E 2 20 it is statisticall$ significant 1,0-!o establish up-to-date Cnormal rangeD values, untreated for ed e/piratory volume in 1 se ond 2B%K13 levels were measured in 1''' individuals sele ted at random from the general population. B%K1 levels were found to follow a normalH?aussian distribution with mean of 8.)' l and standard deviation of '.0) l 2standard error '.',3. .f the normal range for a population is defined as !eing the central 516 of individuals around the mean value" then the normal range for )8K 0 isC 1ean R 1 standard error 2i.e. 8.;@ to 8.), litres3 1ean R , standard errors 2i.e. 8.;: to 8.); litres3 1ean R 1 standard deviation 2i.e. ,.0) to ;.,) litres3 1ean R , standard deviations 2i.e. ,.'' to ).'' litres3 1ean R 8 standard deviations 2i.e. 1.,) to ).0) litres3 Correct answer

)or a statisticall$ normalJAaussian distri!ution" 516 of individuals lie in the range defined !$ mean two standard deviations (thus" answer 9 is correct) Answer 4" mean O two standard errors" defines rather the 516 confidence interval for the estimated mean% thus we can !e 516 certain that the true mean )8K0 level for the general population is in the range - /3 to - 1/ litres 1,@-In a prospe tive lini al trial, 1;' patients with hepatitis were randomly allo ated to re eive either a new drug or onventional treatment7 the patients were followed up for between 8 and ) years. When evaluating the stud$ results" a Chi#s,uare test can !e used to compare the two groups with respect toC !he proportions of patients who died within three years of starting their treatment !he proportions of patients who died within five years of starting their treatment !he proportions of patients who had died when the study was terminated 1edian survival times 1ean survival times The Chi#s,uare test can !e used onl$ to compare categorical measures As survival times are continuous (usuall$ measured in months)" options 9 and 8 are !oth incorrect +urvivalJdeath rates are compara!le onl$ at a fixed point in time following the start of treatment < and all su!7ects must have !een followed up for that length of time When this stud$ was terminated" patients had !een followed up for times ranging from - $ears to 1 $ears" ma'ing option C invalid ;ot all patients were followed up for 1 $ears" so option 4 is also invalid &owever" as all patients were followed up for at least - $ears" option A can !e evaluated using the Chi#s,uare test 1,(-"esponse to all, time to visit, pres ribing and hospital admissions were re orded for ,1), patients who re5uested out-of-hours are from ;( pra ti e do tors and 1@8 deputising do tors. Bor patients visited at home, the mean and median times to arrival for pra ti e do tors were )).; and 8) minutes respe tively 2range . 1', minutes3. Times to arrival are which of the following? 6inary Downwardly 2negatively3 s#ewed $ormally distributed 9pwardly 2positively3 s#ewed Kalid measurements of patient are The mean is much larger than the median and this suggests an upward (positive) s'ewing of the data from this stud$ Correct answer Correct answer

18'-6lood pressures are measured in a group of ,) hildren 2ages 8+1)3. "egression analysis does not show a signifi ant relationship between blood pressure and age 2average in rease in blood pressure per year of age . 1' mmLg, ()* onfiden e interval 2-;' to :'3, P . '.::3. Which of the following should !e concluded? A mu h larger study needs to be underta#en Age affe ts blood pressure 6lood pressure is ompletely unrelated to age 6lood pressure was not reliably measured in this group Older hildren have higher blood pressures This is an o!servational stud$ and cannot prove a causal relationship (so 4 and 8 are incorrect) While older children have" on average" higher !lood pressures this difference is non#significant &owever" the a!sence of statistical significance does not necessaril$ prove the a!sence of a relationship (the stud$ was pro!a!l$ too small to detect it)% furthermore" as the confidence interval is wide we cannot discount the possi!ilit$ of a clinicall$ important relationship (so C is incorrect) There is no evidence that !lood pressure was measured poorl$" so 9 is incorrect A larger stud$ needs to !e underta'en to gain a more precise estimate of the relationship !etween !lood pressure and age 181-Anaestheti re overy time was re orded for 1'' onse utive patients undergoing the same surgi al pro edure. 1ean and median times for the pro edure were ;' and :) minutes respe tively7 the standard deviation was )' and the range () 2,' to11) minutes3. What is the !est wa$ of summarising these data for a paper to a medical 7ournal? 1ean . ;'7 standard deviation . )' 1ean . ;'7 standard error . ) 1ean . ;'7 range . ,' to 11) 1edian . :)7 standard deviation . )' 1edian . :)7 range . ,' to 11) Correct answer Correct answer

The recover$ times clearl$ have a ver$ negativel$ s'ewed (i e non# normalJnon#Aaussian) distri!ution" as shown !$ the large difference !etween the mean and median" and !$ the fact that the median is much closer to the centre of the range than the mean @eans" standard deviations and standard errors are onl$ valid for data with a normal distri!ution" ma'ing A" 4" C and 9 incorrect 8 gives the correct statistics for data with a non#normal distri!ution 18,-A linear regression analysis of data olle ted from a random sample of ,'' normal healthy individuals found that, on average, a ,' #g in rease in weight was asso iated with a ) mmLg 2()* onfiden e interval , to @ mmLg3 in rease in systoli blood pressure 2&6P3.

&ow should this finding !e !est interpreted? !here is a statisti ally signifi ant relationship between weight and &6P Only a small in rease in &6P was asso iated with a large in rease in weight, so a mu h bigger study is needed A person who weighs :' #g will have a &6P that is 1' mmLg lower than a person who weighs 1'' #g >osing weight will lower systoli blood pressure !he relationship between weight and &6P is linear The 516 confidence interval for the increase in +4: associated with a (2 'g increase in weight does not include 2 (*ero)" indicating that the relationship o!served is indeed statisticall$ significant =ption 4 states correctl$ that average +4: increases onl$ slowl$ as weight increases" !ut the relationship has !een esta!lished as !eing statisticall$ significant" so a larger stud$ is unnecessar$ A linear regression line estimates the average relationship < it cannot !e interpreted directl$ for individuals% option C is correct onl$ if restated as people who weigh 32 'g have an average +4: that is 02 mm&g lower than that for people who weigh 022 'g There ma$ indeed !e a causal relationship !etween weight and +4:" !ut this cannot !e inferred from a cross#sectional o!servational stud$ < a longitudinal stud$ is needed to prove option 9 )inall$" it is li'el$ that the true nature of the relationship !etween weight and +4: is more complex than a simple straight line < when we fit a linear regression line to data" we are merel$ approximating the true relationship to a straight line 188-!wo groups were re ruited on the basis of their height at age )+: years. One group was hosen as CshortD and the other, of normal height, a ted as ontrols. At appro/imately 1, years of age the intelligen e 5uotient 2IV3 of the hildren in both groups were measured and the results ompared and the CshortD group had on average lower s ores. !he mean differen e was :., IV points 2()* onfiden e interval 2;.1, @.83, P F '.'13. Which of the following statements interprets the results most accuratel$? A differen e in IV as large as that observed 2i.e. :., IV points3 would have o urred by han e less than one time in 1'' if short hildren at age )+: did not differ from the non-short population in terms of IV at age 1, 6eing short at age )+: years auses a signifi ant redu tion in intelligen e at age 1, IV is not signifi antly related to height IV must be non-normally distributed in these samples $o valid information an be gleaned from this study sin e the measurement of IV is diffi ult and may be observer dependent This o!servational stud$ found that" on average" short people had lower .X scores than normal height children As this difference was statisticall$ significant" C is incorrect &owever" a causal relationship cannot !e inferred" so 4 is also incorrect The 516 confidence interval is s$mmetrical" indicating a normal distri!ution for these data (ma'ing 9 incorrect) =ption 8 is Correct answer Correct answer

nonsensicalZ The :#value is the pro!a!ilit$ of o!taining a difference as great as (or greater than) that o!served if the null h$pothesis of no difference is true < hence option A is correct 18;-A group of 8' patients with asthma underwent treadmill tests on two o asions, four wee#s apart. 6efore the first test, ea h patient was randomly allo ated to re eive either drug A 2standard treatment3 or drug 6 2new treatment37 before the se ond test, ea h patient re eived the alternative drug. !he distan es wal#ed in ea h test were found to follow an appro/imate normalH?aussian distribution. What statistical significance test is !est for comparing the effects of the two drugs? !he Bisher e/a t test !he &tudent unpaired t-test !he &tudent paired t-test !he 1ann+=hitney 9-test !he =il o/on test This is a classic cross#over design RCT (randomised controlled trial) < the same individuals were evaluated under !oth test conditions" so the groups are dependent (paired) The primar$ outcome measure is continuous" with an approximate normal distri!ution As the )isher exact test is used for categorical data onl$" option A is invalid =ptions 4 and 9 are tests that can onl$ !e used to compare independentJunpaired groups (i e studies where each group consists of completel$ different people)" so are invalid here =ption 8 could !e used" !ut this non#parametric test does not ma'e use of the fact that the data follow a normal distri!ution" so is su!optimal The !est test in this situation is option C 18)-An observational study of immunoglobulin ? 2Ig?3 levels was arried in human immunodefi ien y virus 2LIK3- and non-LIK-infe ted individuals. !he two large groups studied were similar with respe t to age and se/7 there are no other potential onfounding fa tors that need to be orre ted for. !he Ig? levels re orded had a positively s#ewed distribution. What statistical significance test is !est for comparing the average .gA levels of the two groups? !he Chi-s5uare test 2 ontingen y table analysis3 !he &tudent unpaired t-test !he 1ann+=hitney 9-test !he &pearman orrelation oeffi ient 1ultiple regression analysis .gA levels have a continuous positivel$ s'ewed statistical distri!ution" so this measure is non#normal The Chi#s,uare test can !e used onl$ to compare categorical measures" so option A is invalid As the groups were compara!le with respect to !oth important confounders" correlation andJor regression anal$ses are not re,uired" ma'ing options 9 and 8 invalid The +tudent unpaired t#test and the @ann<Whitne$ B#test can !oth !e used to Correct answer Correct answer

compare two independent groups% however" the t#test re,uires the data to have a normal distri!ution Thus" option C is the optimum choice for this stud$ 18:-Qou are de iding on additional treatment for a ,,-year-old man who has ontinuing asthma symptoms on )'' m gHday of inhaled fluti asone dipropionate. When reviewing availa!le papers on asthma management" which of the following represents the !est grade of evidence? A randomised double-blind trial of in reased inhaled steroid versus the addition of long-a ting b-agonist therapy An open-label study of in reased inhaled steroid therapy A onsensus statement from a group of e/perts A retrospe tive hart analysis An observational study 8vidence#!ased medicine has developed a s$stem of evidence grading to allow the proper evaluation of therapeutic choices The highest grade of evidence" !eing the randomised dou!le#!lind place!o (or !est alternative therap$)#controlled stud$ These ma$ !e com!ined in a meta#anal$sis if this is appropriate to increase statistical power =pen#la!el studies are considered inferior to !linded studies% next on the ladder of evidence in this ,uestion is the o!servational stud$ Retrospective chart anal$sis and expert consensus are considered the lowest grades of evidence The +cottish .ntercollegiate Auidelines ;etwor' (+.A;) group have applied evidence grading to a num!er of therap$ areas including the management of asthma The 4ritish Thoracic +ociet$J+.A; guidelines represent the !est availa!le evidence#!ased evaluation of asthma management 0-F#&ow is the power of a statistical test !est defined? !he probability of not re-e ting the null hypothesis when it is false !he probability of not re-e ting the null hypothesis when it is true !he probability of obtaining a statisti ally signifi ant result !he probability of re-e ting the null hypothesis when it is false !he probability of re-e ting the null hypothesis when it is true )irst" note that options A and 8 represent errors% 8 is a t$pe#0 error" and A is a t$pe#( error =ptions 4 and 9 are favoura!le < a powerful test is li'el$ to re7ect the null h$pothesis when it is false =!taining a statisticall$ significant result ma$ !e good or !ad depending on whether that result is true or not We must alwa$s remem!er that statisticall$ significant results can occur !$ chance 18@-Con ern has been e/pressed that low birthweight 2>6=3 hildren have impaired motor s#ills when starting s hool. !o test this hypothesis, motor development inde/ Correct answer Correct answer

21DI3 was measured in 8' >6= and 8' normal birthweight hildren, all of whom were aged ) years. The results of this stud$ are !est summarised !$C 1ean and ()* onfiden e interval for ea h group separately 1ean differen e between the two groups and its ()* onfiden e Correct interval answer 1ean and standard error for ea h group separately Differen e between the two groups and its standard error 1ean and standard deviation for ea h group separately All of these are used regularl$ in 7ournals" so none are actuall$ wrong < !ut as the primar$ o!7ective is to determine the si*e of an$ difference in motor development !etween the two groups of children" 4 is the !est of the options The 516 confidence interval around the mean difference indicates the most li'el$ range of values for the true difference in motor development at 1 $ears )urthermore" if the 516 confidence interval does not include 2 (*ero)" the difference is statisticall$ significant !he birthweights of 1'' babies born to drug-abusing mothers were summarised as followsA mean . ,)'' g, standard deviation . )'' g. 0-5#Which stem !est descri!es the (approximate) 516 confidence interval for the mean !irthweight? 1ean R 1 standard deviation 2i.e. ,''' to 8''' g3 1ean R , standard deviations 2i.e. 1)'' to 8)'' g3 1ean R 1 standard error 2i.e. ,;)' to ,))' g3 1ean R , standard errors 2i.e. ,;'' to ,:'' g3 !he ()* onfiden e interval annot be omputed from the information provided Appro/imate ()* onfiden e intervals are omputed from the formulaA mean R two standard errors. &tandard error . standard deviation \ s5uare root of sample si<e. !husA standard deviation . )'' \ v21''3 . )'' \ 1' . )' ()* onfiden e interval . ,)'' R 2, / )'3 . ,)'' R 1'' . ,;'' to ,:''. In a group of hildren the heights are normally distributed. 1 in ;' of the hildren is shorter than )' m and 1 in ;' is taller than 0' m. 0/2#Which of the following statements !est descri!es the statistics which descri!e their heights? 1ean height . )' m, median . 0' m, standard deviation . 1' m 1ean height . :' m, median . :' m, standard deviation . 1' Correct answer

m 1ean height . )' m, median . )' m, standard deviation . ) m 1ean height .0' m, median . :' m, standard deviation . 1 m 1ean height .:' m, median . :' m, standard deviation . ) Correct m answer Bor normally distributed data, appro/imately ()* of the values lie in the range mean R , standard deviations 2&D3. !hus, ,.)* 2or 1 in ;'3 will be less than mean + ,&D, and a further ,.)* 21 in ;'3 will be greater than mean E,&D. Bor the distribution des ribedA 1ean + ,&D . )' 1ean E ,&D . 0' Burthermore, the data are symmetri al 2sin e the distribution is normal3. Len e mean . :' and median . :' 2for a normal distribution mean . median3, and the &D . ).