Epidemiology (2009)

Outline
Unit 1. Introduction Unit 2. Measures of Epidemiology Unit 3. Met ods of !tudy Unit ". #isease !creening Unit $. #escripti%e Epidemiology Unit &. In%estigation of an epidemic Unit '. Ecological !tudy Unit (. )ross*!ectional !tudy Unit (. )o ort !tudy Unit 10. )ase*)ontrol !tudy Unit 11. Inter%ention !tudy Unit 12. +aria,ility and -ias Unit 13. Interpretation of Epidemiologic .iterature Unit 1". /eadings /eference0 19(3 /ot man and 1reenland. Modern Epidemiology. 2nd Edition. .ippincott*/a%en. 2 ilidelp ia. 199(. 0&*2'($123311( su sing3mail.c4cu.edu.t5

Unit 1. Introduction
Epi 6 among (1ree7) #emos 6 people (1ree7) .ogos 6 doctrine (1ree7) Epidemiology0 #efinition0 Epidemiology is t e study of disease (in4ury8 disa,ility or deat ) occurrence in uman populations. 9 e primary units of concern are groups of persons8 not separate indi%iduals. (!"#$%&'()(*+,-.,/0)12345!"6789: %#;4<=>6:?&) @ABCDEFG1HIJK$:;LMB<NOPQ2RST)UV WCLXYZ<[\],2,,^,_`,2ab,c2a ,de,fghij;klB<mnLMBCopYZqr stUVuJ;vwB<xyz{vw)C12<|}(

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EFG ( Survi val Curve)

100% 80%

E H (%)

60% 40% 20% 0% 0 6 16 26 36 46 56 66 76

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Unit 2. Measures of Epidemiology

)ount ()0 Male and >emale in )lass /atio (E)0 eFpress t e relations ip ,et5een t5o num,ers in t e form @0A or FEy G 7 2roportion (E)0 a specific type of ratio in 5 ic t e numerator is included in t e denominator. MaleE9otal Measures can c aracteriHe0 1. One point in time0 e.g.8 num,er of motorcycle accidents in 1E1E1999 2. ? period of time0 e.g.8 num,er of motorcycle accidents during 1E1E1999*12E31E1999 a a. ?%erage c ange per unit of time 6 a rate ,. )umulati%e c anges 6 a pro,a,ility8 or ris7 estimation /ate0 num,er of people t at de%elop disease during t e specified time period. Units of time (e.g.8 person*years) t e people 5ere capa,le of de%eloping t e disease during t e specified period /is7E2ro,a,ility I num,er of people t at de%elop disease during t e specified time period Jum,er of people at ris7 (at*ris70 capa,le of de%eloping t e c aracteristics) person*years0 eKui%alent num,er of people 5 o 5ould a%e ,een at ris7 for one full year for eFample0 1000 person*years eKuals0 2eople 1000 $00 2$0 200 100 9ime*at*ris7 (a%erage) 1 year 2 years " years $ years 10 years or >emaleE9otal

Under t e assumption t at e%ery person*year as t e same ris7 for diseases8 in fact8 5e 7no5 it is not true since a person*year contri,uted from a se%enty year*old men is more %ulnera,le to diseases t an a person*year contri,uted from a t5enty year*old young men.

/is7 and /ate )alculation0 1000 elderly identified ;anuary 18 1990 300 deat s during 1990 /is7 (pro,a,ility) of deat I (300E1000)L1000I 300 (deat s per 18000 persons) /ate of deat I 300E('00 C 1$0) I300E($0 (300E($0) L 1000 I 3$2 (per 18000 person*years) Under t e assumption t at 300 deceased cases 5ere dead at t e time eKually distri,uted in t is one*year period. In a fi%e years o,ser%ation8 1000 elderly identified ;anuary 18 1990 >irst year 20 died !econd year 30 died 9 ird year 30 died >ourt year 2$ died >ift year $0 died 9otal 1$$ died during t e fi%e year period8 please calculate ris7 and rateM /is7 I 1$$E1000 I 0.1$$ 2erson*years0 Aear one Aear t5o Aear t ree Aear four Aear fi%e #eat 20 30 30 2$ $0 2erson*Aears 9(0C10I990 9$0C1$I9&$ 920C1$I93$ (9$C13I90( ("$C2$I('0 9otal person*years I 990C9&$C93$C90(C('0I "&&( /ate I (1$$E"&&() L18000 I 33 (per 18000 person*years)

&

2re%alence depends on t5o factors 1. 9 e num,er of people 5 o a%e ,een ill in t e past 2. 9 e duration of t eir illness 2I IL# (I L #) C1 I0 Incidence (12) #0 #uration ()

N N

#isease pre%ention8 migration 9reatment8 #isease fatality

3.

If t e incidence and duration a%e ,ot ,een sta,le o%er a long period of time8 t en t is formula ,ecomes 2 I L # !eldom is pre%alence of direct interest in etiological applications of epidemiologic researc . !ince pre%alence reflects ,ot t e incidence rate and t e pro,a,ility of sur%i%ing 5it disease8 studies of pre%alence or studies ,ased on pre%alence cases yield associations t at reflect t e determinants of sur%i%al 5it disease 4ust as muc as t e causes of disease. (!"n<k)(12E <*(Ij) :ig pre%alence does not necessarily signify ig ris7O it may merely reflect an increase in sur%i%al. .o5 pre%alence may reflect a rapidly fatal process or rapid cure of disease as 5ell as lo5 incidence. (A<E* +38)+/U) ( p.102) 2re%alence is important8 particularly in c ronic disease8 in determining 5or7load8 as it is a useful tool for t e planning of facilities and manpo5er needs. (zwU <({wU(#a) 2eriodic estimation of point pre%alence is useful in trac7ing c anges in disease patterns o%er time. 2oint pre%alence can ,e determined ,y a series of cross*sectional sur%eys. (({%)C?3is )

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Incidence (12)

Incidence rates are t e fundamental tool for etiologic studies of ,ot acute and c ronic disease8 since t ey are direct indicators of ris7 of disease. (;(L XW<A)()

)ertain ,asic reKuirements must met if incidence rates are to ,e calculated0 a. Pno5ledge of t e ealt status of t e study population. 9 ere must ,e adeKuate grounds on 5 ic to assess t e ealt of indi%iduals in a population and to classify people as QdiseasedR or Qnot diseased.R (P)S)
,.

9ime of onset. #etermination of date of onset is necessary for studies of incidence. >or c ronic disease and cancer8 t e date of onset is defined ,y t e date of definiti%e diagnosis. (Y)1(') !pecification of numerator0 num,er of persons %s. num,er of conditions. In certain circumstances8 more t an one e%ent can occur to t e same person 5it in a stated time period. (;#12P) Jum,er of people 5 o de%eloped a cold in one*year period 2eople at ris7 in one*year period

c.

e.g.8

(9 e ris7 (pro,a,ility) t at any person 5ill de%elop a cold in one yearO usually if not specified 5e assume persons to ,e numerator) Jum,er of colds in one*year period 2eople at ris7 in one*year period (9 e num,er of colds to ,e eFpected among t e group of people in a year)
d.

!pecification of denominator. 9 e denominator s ould not include t ose 5 o are not suscepti,le to t e disease (not at ris7). In a large population8 t is correction is not made due to practical pro,lems. (?nnual rates usually use t e estimated midyear population). (I;)

e. 2eriod of o,ser%ation. It is important to al5ays state t e definite time period.

)alculation0 !tudy period0 from ;anuary 18 1990 to #ecem,er 318 199$ 1990.1.1 ? ) # E > 1 : I ; P 1991 1992 F 1993 199" 199$ #ec 318199$ F dead SSSSSS ealt y disease A

F F

2oint pre%alence of disease A on t e day of ;anuary 18 199$ is SSSSSS . 2eriod pre%alence of disease A during t e study period is SSSSSSS . /is7 of disease A during t e study period is SSSSSSS . /ate of disease A during t e study period is SSSSSSS .

EFercise0 20000;;!"<z19991111&0#ut<: C<z199912311007!12tu<: <z20001231(07!12Ctu<zC: <20011231&07!1Cu 1 z!"%<J'Ct12(Incidence rate); 2 z!"%<J'Ct12(ris7); z!"%<z199911Ct;

!tandardiHation of rates0 )rude /ate I total num,er of cases 9otal person*time or population at ris7

!tandardiHation0 1. /emo%es t e distortion introduced ,y different age distri,utions across populations (C()*I()/0) 2. It pro%ides t e opportunity to eFamine disease rates 5 ile olding t e effect of age constant. (%&'9zICN@o()/0) e.g.8 9otal num,er of lung cancer deat s 1$& 122 1990 population 1181&1 "8'00 )rude deat rate (per 1000) 1".9( 2$.9&

>arming area Industrial area

#irect met od0 In t e direct met od8 age*specific rates o,ser%ed in t5o or more study populations are applied to an ar,itrarily c osen population of 7no5n age structure referred to as a QstandardR population. (z'<!"%&(/0 ;%&((%&)(Iq) In t e farming area Jum,er of ?ge*!pecific !tandard ?ge*standardiHed lung cancer deat rate 2opulation deat rate (per deat s ( per 1000) 2roportions 1000) T1$ 23"( 2 0.($ 0.2(( 0.2" 1$*29 "1$' 1$ 3.&1 0.2"3 0.(( 30*39 12"3 & ".(3 0.111 0.$" "0*"9 9$9 1$ 1$.&" 0.120 1.(( $0*$9 ($3 23 2&.9& 0.10& 2.(& &0*&9 ''2 3" "".0" 0.0'" 3.2& '0C (29 &1 '3.$( 0.0$9 ".3" 9otal 1$& 1".0 < !tandard 2opulation 2roportions usually come from an ar,itrarily c osen population of 7no5n age structure referred to as a standard population. < ?ge*specific deat rate I num,er of deat s at a specific age during a periodE a%erage population for t is specific age during a period ?ge 1990 2opulation

In industrial area0

10

?ge T1$ 1$*29 30*39 "0*"9 $0*$9 &0*&9 '0C 9otal

1990 2opulation 101$ 1193 ""1 "30 ""9 "'9 &93

Jum,er of lung cancer deat s 0 3 3 ' 1$ 2" '0 122

?ge*!pecific deat rates (per 1000) 0 2.$ &.( 1&.3 33." $0.1 101.0

!tandard ?ge*standardiHed 2opulation deat rates (per 2roportions 1000) 0.2(( 0 0.2"3 0.&1 0.111 0.'$ 0.120 1.9& 0.10& 3.$" 0.0'" 3.'1 0.0$9 $.9& 1&.$

Indirect met od0 1. Indirect met od is used to compare t5o populations8 in one of 5 ic t e age*specific rates are not 7no5n or8 if 7no5n8 are eFcessi%ely %aria,le ,ecause of small num,ers. ((%&:/0Y/0=< n') 2. In t is met od8 t e more sta,le rates of t e larger population are applied to t e population of t e smaller study group.(z'<K%&(/0 nz%&) 3. )omparison of t e num,er of eFpected deat s in t e smaller population 5it t e num,er actually o,ser%ed yields a measure 7no5n as t e !tandardiHed Mortality /atio (!M/). !M/IO,ser%ed deat sEEFpected deat s ?ge #eat rates in 1990 standard population in population industrial (per 1000) area 0.&2 101$ 3.'1 1193 $.$2 ""1 13."3 "30 3&.'1 ""9 '2.32 "'9 (3.(3 &93 EFpected num,er of deat s 0.&3 "."3 2."3 $.'' 1&."( 3".&" $(.09 122."' O,ser%ed num,er of deat s 0 3 3 ' 1$ 2" '0 122

T1$ 1$*29 30*39 "0*"9 $0*$9 &0*&9 '0C 9otal

!tandardiHed Mortality /atio (!M/) I O,ser%ed num,erEeFpected num,er F 100 )onclusion0 (122E122."') F 100 I 99

11

?ge

T1$ 1$*29 30*39 "0*"9 $0*$9 &0*&9 '0C 9otal

#eat rate in population in standard farming area population (per 1000) 0.&2 23"( 3.'1 "1$' $.$2 12"3 13."3 9$9 3&.'1 ($3 '2.32 ''2 (3.(3 (29

EFpected num,er of deat s 1."$ 1$."2 &.(& 12.(( 31.31 $$.(3 &9."9 193.2"

O,ser%ed num,er of deat s 2 1$ & 1$ 23 3" &1 1$&

!M/I (1$&E193.2") F 100 I (1

;#\yP,yPTyPC/0t#`a[@ yP yP # # # /0 /0 /0 30 N 39 "08000 10 "008000 20 (80008000 300 "0 N $9 308000 20 "008000 $0 (80008000 '00 U I &0 308000 30 "008000 2$0 &80008000 28000 (1)9yP;%&<yPC/0(!M/); (2)9yP;%&<9yP(b/0

12

2roportional Mortality /ate I num,er of deat s due to a particular cause (/E2M/) 9otal num,er of deat s 2M/ is used 5 en t e li%ing population at ris7 for t e o,ser%ed deat s can not readily ,e enumerated (%&Y<Yo/x) 2. In t e ope t at a ig proportional mortality rate for a particular condition reflects a ig true mortality rate for t at condition.(92M/qo/(/0) 3. ? ca%eat 5 ile applying 2M/8 a ig proportional mortality can also ,e caused ,y a deficiency of deat s from ot er cause.( 2M/k/*)
1.

199" 199$

#eat s 2M/ #eat s 2M/

2oliceman "0 0.1$ (0 0.2' 2oliceman "0 0.1$ "0 0.21 (0 0.21

>armer 20 0.0( 20 0.0' >armer 20 0.0( 20 0.10 "0 0.10

Industry >is erman Ot ers 100 "0 &0 0.3( 0.1$ 0.23 100 "0 &0 0.33 0.13 0.2 Industry >is erman Ot ers 100 "0 &0 0.3( 0.1$ 0.23 (0 "0 10 0."2 0.21 0.0$ 1&0 (0 20 0."2 0.21 0.0$

199$ 199& 199'

#eat s 2M/ #eat s 2M/ #eat s 2M/

If t e populations among eac occupation a%e not c anged in t ese years 2opulation #eat s #eat /ate #eat s #eat /ate #eat s #eat /ate 2oliceman 1000 "0 0.0" "0 0.0" (0 0.0( >armer 108000 20 0.002 20 0.002 "0 0.00" Industry >is erman "08000 $000 100 "0 0.002$ 0.00( (0 "0 0.002 0.00( 1&0 (0 0.00" 0.01& Ot ers 1008000 &0 0.000& 10 0.0001 20 0.0002

199$ 199& 199'

13

/ate #ifference0 -y su,tracting t e smaller from t e larger8 one may o,tain t e magnitude of t e rate difference. () ?ttri,uta,le /is7 0 t e difference ,et5een t5o incidence rates. (C) e.g.8 in :ammondVs (199&) study of smo7ing and mortality0 .ung cancer mortality rate in nonsmo7ers aged $$*&9I 19 per 1008000 person*years in smo7ers age $$*&9I 1(( per 1008000 persons*years /ate difference I 1&9 per 1008000 person*years !mo7ing cigarette produce 1&9 lung cancer cases per 1008000 person*years ?ttri,uta,le ris7 percent (H) (etiologic fraction () or attri,uta,le fraction)0 is t e difference ,et5een rates ,et5een t e eFposed and non*eFposed di%ided ,y t e rate in t e eFposed 1&9 per 1008000 person*yearE1(( per 1008000 person*years I 1&9E1(( I 0.9 !mo7ing produced 90W of t e lung cancer cases among smo7ers. ?mong smo7ers8 90W of t e lung cancer 5ere attri,uta,le to smo7ing. 2opulation ?ttri,uta,le /is7 (2?/O %C)0 /p * /uneFp 2opulation ?ttri,uta,le /is7 2ercent (2?/WO%)0 (/p * /uneFp )E/p Eg.8 19(02008000 <~<<NO;<, ,h3<1 <NO # # 121 &&08000 2$ 2008000 &2 10&08000 20( 189208000 t <;z<*IC;z%*IC;

1"

Unit 3 Met ods of !tudy O,ser%ational () %ersus EFperimental (nZ) %ersus Xuasi*EFperimental (nZ) #escripti%e () %ersus ?nalytic () 2rospecti%e () %ersus /etrospecti%e ()

EFperimental %ersus Xuasi*EFperimental %ersus O,er%ational a. In eFperimental study8 t e in%estigator acti%ely inter%enes and ma7es one %aria,le c ange and t en sees 5 at appens to t e ot er. (znZ!"8!" 4?Cvt;:8_) ,. 9 e sole difference ,et5een eFperimental and Kuasi*eFperimental is t at Kuasi* eFperimental study does not a%e t e control on assigning su,4ects to eFposed or non*eFposed group (lac7 of randomiHation). !u,4ects are usually self*selected in assigning t emsel%es to eFposed or non*eFposed groupO or sometimes t e researc ers ar,itrarily assign su,4ects into groups. ?nd8 sometimes8 t ere is no control group at all. (nZC!"8?=j3 ? !" nZ) c. In o,ser%ational study8 natural is allo5ed to ta7e its course8 and c anges or differences in one c aracteristic are studied in relation to c anges or differences in t e ot er8 if any. (z!"88;12C 12CW)

EFperimental0 manipulate study factorO randomiHe study su,4ects Xuasi*eFperimental0 manipulate study factorO no randomiHation of study su,4ects O,ser%ational0 no manipulation of study factorO no randomiHation of study su,4ects EFperimental ?d%antages0 control o%er eFtraneous factorsO t e results can ma7e a strong statement of t e cause and effect relation .imitations0 O%er control of eFtraneous factorsO Jot natural settingO t e result is ard to generaliHed to t e general population8 e.g.8 2ractical issues of implementation a. /andomiHation not et ical0 sometimes itVs not et ical to randomiHe persons to ris7 factors ,. #esign t at is not feasi,le0 sometimes8 doing a community inter%ention8 to see if sunscreen can protect s7in cancerO o5e%er8 t e control ,eing contaminated ,y t eir co*5or7ers8 t e tele%ision8 t e magaHine. Xuasi*EFperimental0 !tudies may a%e eFperiment and control groups8 ,ut su,4ects are not randomiHed into eac group.

1$

 !tudies may a%e only one group (eFperiment group)8 t ere is no control group for comparison. 2eople usually compare ,efore and after using certain indeFes. =e donVt 7no5 t e outcome of not implementO 5e only 7no5 t e outcome of implement. ?d%antages0 More feasi,ility and less eFpensi%e t an eFperimental study .imitations0 .ess control of eFtraneous factors EFperiment

EFperiment

O,ser%ational study falls into t5o categories0 descripti%e a. ) aracteriHe a situation. (;12) ,. #escripti%e approac c aracteriHes t e distri,ution of somet ing ,ut does not necessarily try to eFplain t e underlying reasons for t e distri,ution. ( z 8z\) c. Usually in%ol%e t e determination of t e incidence8 pre%alence8 and mortality rates for diseases in large population groups according to ,asic group c aracteristics8 suc as age8 gender8 race (demograp ics) and geograp ic data. (%&C8[,,Ty8:%&; (12,T/0) ?nalytic a. EFplain 5 y t e situation occurs0 a%e at least one eFposure and one outcome. (\;1212(<:;0<:;I) ,. 9 e staring point for an analytic study is often a descripti%e finding t at raises certain Kuestions or suggests certain ypot eses t at reKuire furt er in%estigation. (!"{!"<1$t"=: !) #escripti%e studies

1&

?nalysis of results

Model*,uilding and formulation of ypot eses ?nalytic studies to test ypot eses

2rospecti%e %ersus /etrospecti%e EFposures Outcomes

2rospecti%e /etrospecti%e 2rospecti%e study0 EFposure measurements are made ,efore t e outcomes occur. (0 C'"zI() ,. /etrospecti%e study0 EFposure measurements are made after t e outcomes occur. (0 C'zI() c. Early 5riters referred to co ort studies as prospecti%e studies and to case*control studies as retrospecti%e studies. :o5e%er8 during current epidemilogical study design8 ,ot co ort study and case*control study can ,e prospecti%e and retrospecti%e.
a.

1'

Unit ". #escripti%e Epidemiology

#escripti%e Epidemiology0 #escription of t e eFposures and outcomes 2ersonE5 o 9imeE5 en 2laceE5 ere 2urpose of descripti%e studies0 a. ?lerting t e medical community to 5 at types of persons are most li7ely to ,e affected ,y a disease8 5 ere t e disease 5ill occur8 and 5 en. (OPBW)Cv#) ,. ?ssisting in t e rational planning of ealt and medical care facilities. ($%S TBV#&) c. 2ro%iding clues to disease etiology and Kuestions or ypot eses for furt er fruitful study. (OPW)(,T")

1(

Unit $. Ecological study (2Y!")0

a. O,ser%ation of disease and eFposure on t e group ,asis. # E E a c aCc # , d ,Cd aC, cCd J

In ecological study8 5e 7no5 t e data ,y group0 aCc8 ,Cd8 aC,8 and cCd. =e do not a%e information on indi%idual cells0 a8,8c8and d. Ecological >allacy (2Y'()0 9 e failure of eFpected ecological effect estimates to reflect t e ,iologic effect at t e indi%idual le%el. (2Y!"I)*+,-?#.(2ab) EFamples0 /esearc ers found suicide rate is associated 5it areas 5 ere )at olics li%es (19$1). .atter8 some researc ers found t at in t ese area also li%es many minorities 5it %ery ig suicide rate8 in contrast8 )at olics as lo5 suicide rate. !ummary of Ecologic !tudies ?d%antages0 1ood for 1enerating ypot eses IneFpensi%e Xuic7 and simple .imitations0 2opulation information may not apply to indi%iduals #ifficult to deri%e precise estimates of eFposure andEor disease Jo control for eFtraneous factors (confounding)

19

Unit &. )ross*!ectional !tudy (is!")

Includes all persons in t e population at t e time of ascertainment or a representati%e sample of all suc persons as su,4ects. (!"?/0`a1%&(*# WA(:%#) ,. EFposure status and disease status are measured at one point in time or o%er a s ort period of time in t e study su,4ects. (0NO)Yz:'V1) c. ? cross*sectional study conducted to estimate pre%alence is called a pre%alence study.
a.

In a nuts ell8 select J t en determine t is distri,ution of E and # # E E a c aCc # , d ,Cd aC, cCd J

!ummary of )ross*!ectional !tudies ?d%antages0 a. 2articularly useful for 1. >reKuent diseases of long duration (283()) 2. #etermining c aracteristics of a population (4\%&() 3. Estimating t e pre%alence of a disease ()() ". 1enerating ypot eses of eFposure 6 disease relations ips (50)(" ) ,. 1eneraliHa,ility8 due to t e 5ays t at t e su,4ects are recruited into t e study. (6 7;:%&<%&=8A9) .imitation0 a. Jot useful for rare diseases or diseases 5it s ort duration (:{!";2() ) ,. )ause*effect relations ip tenuous (temporality)O it may ,e impossi,le to determine 5 ic came first. (e.g.8 do people in lo5 social classes a%e ig er pre%alence rates of many mental illness t an do people of ig er social classes8 or do people migrate do5n t e social class scale once t ey ,ecome mentally ill and are t erefore found in t e lo5er social classes at t e time a study is doneM) (zI<V(=)I5) c. >or disease is in remission may ,e falsely classified as not a%ing t e disease. (> s() ?(9;) d. 2eople eit er reco%er or die from a disease Kuic7ly as less of a c ance of ,eing included in t e disease group. If c aracteristics of persons 5 ose disease is eit er of s ort duration or rapidly fatal are different from t ose 5 ose disease is of long duration8 t en t e eFposure*disease association o,ser%ed in a cross*sectional study 5ill misrepresent t e association of eFposure 5it incidence. (*1(?@A{

20

3<[I3HB(Cr/0)(*< !"(0)12(I< D(l((v)

21

Unit '. )o ort !tudy (A!")

# E E a c aCc # , d ,Cd aC, cCd J

/esearc strategies0 a. 2rospecti%e (,) 6 9 e in%estigator collects information on t e eFposure status of t e study su,4ects at t e time t e study ,egins8 and identified ne5 cases of disease (or deat s) from t at time on!"<!"1*!"%&( 0`a<E1)1(NO ,. /etrospecti%e (,FG) 6 9 e in%estigator identifies t e eFposure c aracteristics of a co ort in t e past and t en reconstructs t e su,seKuent disease eFperience up to some defined point in t e more recent past or up to t e present time. (!"HI;%&C0`a<10x()1 NO) c. /etrospecti%e co ort studies a%e some distinct ad%antages o%er prospecti%e co ort studiesO in particular8 t ey can ,e completed in a muc more timely fas ion and are t erefore considered less eFpensi%e. (FGJB'KI<LM) d. In /etrospecti%e co ort studies8 t e in%estigator may a%e t e pro,lems in determining eFposures8 5 ile in prospecti%e co ort studies8 t e in%estigator can actually measure t e eFposures t oroug ly. (zFG0YNO<z0n () !ources of co orts(AC$)0 a. !pecial eFposure groups (A) 1. :ig occupational eFposure 2. !mo7ers 3. 2ersons 5it unusually ig or lo5 p ysiologic measurement8 e.g.8 c olesterol or ,lood pressure (WPZQ) ,. !pecial resource group (`aqL) 1. 2repaid medical care plans (R`a) 2. 2 ysicians 3. Insured persons ". +eterans $. )ollege graduates c. 1eograp ically defined group (}{:yP) 1. >raming am8 Massac usetts !election of comparison groups0

22

a.

,.

c.

d.

e. f.

Internal comparison group (R)0 One group is initially defined and t en di%ided into eFposure categories (zC%&0NO=P0>0 %)(usually8 relati%e ris7 and mortality rate are calculated) EFternal comparison group(Sq)0 = en t ere is no non*eFposed su,*group eFisted in t is co ort8 a eFternal population is soug t8 e.g.8 general population8 anot er factories8 etc. (usually8 mortality rates are comparedO rate ratios or !M/) (%& )P0Y<TU:)0(%&) Multiple0 ? com,ination of t e a,o%e (Internal and EFternal comparison groups). ! ould t e comparison groups gi%e different results8 t en t e in%estigator must try to find out 5 y t e results are different. (RTSqTn) :ealt y*5or7er effect (S#b)0 =or7ers are on t e a%erage ealt ier t an t e general population and 5ould ,e eFpected to a%e lo5er disease rates. (V :WKXS<)) Jote t at t e possi,ility of self*selection into t e initial eFposed and uneFposed groups al5ays needs to ,e considered. (YZ[C0NObv) )areful t oug t must enter into t e c oice of t e comparison group and of t e measurements to ,e made on all co ort mem,ers so t at eit er t e uneFposed co ort mem,ers are firmly ,elie%ed to ,e compara,le to eFposed co ort mem,ers8 eFcept for t e eFposure8 in t e li7eli ood of de%eloping t e disease. (Z[b\] <>0C4>0S<0)

!ources of Information on EFposure (0`aqL)0 a. ?%aila,le /ecords (I) ,. Inter%ie5s (^^) c. Medical eFamination (BV) d. Measures of t e en%ironment (g`a) !ummary of co ort studies0 a. ?d%antages 1. #irect determination of ris7 or rate (9ris7 rate) 2. !tronger e%idence of eFposure and disease association(OP0)'C[
) 3. ".

2ro%ides e%idence a,out lag time ,et5een eFposure and disease (OP0)
'C[)

Easier to generaliHe findings (1_N<mn) ,. .imitations0 1. 9a7e a long time (`) 2. #ifficult to implement and carry out (an&KI ) 3. -ig dimes (``) ". .ost to follo5*up (!"Nb )

23

/elati%e /is7 (//)E/is7 /atio0 a ratio o,tained ,y di%iding ris7 of one group (usually eFposed group) ,y ris7 of anot er group (usually uneFposed group) (W) #isease Aes a EFposed EFposure Jon*eFposed c d cCd , Jo 9otal aC,

// I aEaC, cEcCd e.g.8 association ,et5een use of artificial s5eeteners and ,ladder cnacer. Aes 130 EFposed ?rtificial s5eeteners Jon*eFposed 222 '000 '222 -ladder )ancer Jo "000 9otal "130

// I 130E"130 I 1.02 222E'222 9 ose 5 o eFposed to artificial s5eeteners a%e 2W ig er c ance t an t ose 5 o did not to de%elop ,ladder cancer. 9 e ris7 of de%eloping ,ladder cancer for t ose 5 o eFposed to artificial s5eeteners compared to t ose 5 o did not is 1.02. +ery close to 1.08 t at means t ere is pro,a,ly no association ,et5een artificial s5eeteners and ,ladder cancer. -e cautious in applying 1.0 cut point.

2"

Unit (. )ase*control study!"

a.

2ersons 5it a gi%en disease (t e cases) and persons 5it out t e gi%en disease (t e controls) are selectedO t e proportions of cases and controls t at a%e certain ,ac7ground c aracteristics are t en determined and compared. (z!"<I :%:%)<%&C0c<)

,. In a nuts ell8 >rom effect to cause # E E a c aCc # , d ,Cd aC, cCd J

d. !ources of cases (?qL)0 1. Ideally0 ?ll incident cases in a defined population in a specified time periodO e.g.8 a tumor or disease registry8 or a +ital !tatistics -ureau (?q ;%&C;:'<[)d`ae) 2. In t e real 5orld0 .ogistics may restrict case selection to one or a fe5 medical facilities. (n<?q;BfCu) e. )a%eats in selection of cases(?Z[b 1p)0 1. /epresentati%eness of t e cases deri%ed from special care facilities (q =gC?bWA) 2. 2re%alent cases ma7e it difficult to separate c aracteristics t at are causal or conseKuentialO usually8 incident cases are used in t e study. (bTn12?) f. !election of )ontrols ((Z[)0 1. Ideally0 ! ould a%e t e same c aracteristics as t e cases8 eFcept for t e eFposure of interest. (C4!"(0<b?W() 2. In t e real 5orld0 rarely ac ie%edY (nh) g. !ources of )ontrols0 1. 2opulations0 9otal population8 random sample (%&=<7) 2. 2atients from same ospital as t e cases (q:iBfCu) 3. /elati%es of cases0 !pouses8 si,lings (#Cj) ". ?ssociates of cases0 >riends8 co*5or7ers8 neig ,ors (#C#) !ources of )ontrols0 a. 2opulation0 1. ?d%antage0 More representati%e
2$

2. .imitation0 EFpensi%e and lo5 participation possi,le ,. 2atients from same ospital as t e cases0 1. ?d%antage0 ) eap8 Kuic78 more li7ely to participate 2. .imitation0 May not ,e representati%e c. /elati%es of cases0 1. ?d%antage0 1ood 5ay to control for ot er %aria,les8 e.g.8 socioeconomic status8 education8 et nic status 2. .imitation0 EFpensi%e and time consumingO may end up controlling for an important (unidentified) ris7 factor

2&

Matc ing () a. 9 e pairing of one or more controls to eac case ,ased on certain c aracteristics. (; <?I:7) ,. Matc ing in case*control study 5ill introduce ,ias into t e study. (?C l+3A!"( )) c. 9o en ance study precision. (k!"(H3confidence inter%al lm K ) d. +aria,les selected in matc ing s ould ,e controlled latter in t e data analysis. (n?Z [;(bz!"9de)

!ummary of case control studies0 a. Xuic7 ,. Easy c. /elati%ely ineFpensi%e d. More easily repeated e. 2articularly useful for rare diseases .imitations0 a. #ifficult to 7no5 representati%eness of t e cases and controls ,. In some cases8 may not pro%ide a direct measure of ris78 only odds ratio can ,e o,tainedO in some cases8 if t e population ser%ed as controls8 rate can ,e o,tained. c. 2ossi,ility of introduction of ,ias0 selection ,ias8 follo5*up ,ias8 information ,ias

2'

Odds /atio0 a tec niKue for estimating relati%e ris7 (o) #isease status )ase )ontrol a EFposed EFposure Jon*eFposed c d cCd , 9otal aC,

O/ I e.g.8

aE, cEd

or

adE,c

:eart ?ttac7 )ase )ontrol 30' EFposed 2 ysical inacti%e Jon*eFposed 122 $80'0 '8$2(

9otal '(3$

$192

O/ I

30'E'$2( I 1.&9 122E$0'0

If it is a rare disease8 O/ is close to //. U1 I1 T1 positi%e correlation (ris7 factor) Jo correlation Jegati%e correlation (protecti%e factor) not statistically significant

9$W confidence inter%alincluding 1

/ate /atio0 /ate (usually incidence rate) for eFposed di%iding t e rate for non*eFposed.

2(

Unit 9. Inter%ention !tudies (p!")0

9o test efficacy of a pre%enti%e or t erapeutic measure. a. )linical trial (klZ)0 1. 9 e focus is on indi%iduals 2. #uration ranges from days to years 3. 1enerally restricted to a ig ly selected population ,. )ommunity trial(PZ) 1. 9 e focus is on group or community outcomes 2. .onger duration (U & mont s) 3. Usually primary pre%ention )linical trial0 2opulation !election of eligi,les !ample

Jonparticipants

/andomiHation

Inter%ention 1roup

)ontrol 1roup

.ost 9o >ollo5*up Measure Outcome Measure Outcome

29

2rocedures to reduced ,ias in assessment of outcome in a clinical trial0 a. !ingle ,lind design 6 !u,4ect is una5are of inter%ention group 1. Informed consent already o,tained 2. EFperimenter must treat and monitor all groups in a similar manner ,. #ou,le ,lind design 6 !u,4ect and eFperimenter are una5are of t e group assignment 1. 2lace,o or treatment agents come in a pre*assigned container 2. ?ll su,4ects treated and monitored in a similar manner !ummary of clinical trial0 a. ?d%antages0 1. 1reatest control o%er t e study situation 2. /andomiHation reduces confounding ,. .imitation0 1. )ontrol may lead to QartificialR setting8 limit a,ility to generaliHe 2. Et ical dilemmas 2.1. =it olding ,eneficial treatment 2.2. = en to stop ,ecause of side*effect 3. ?d erence to protocols may ,e difficult to enforce ". #esign may not ,e feasi,le ".1. Manipulation of a psyc osocial attri,ute (e.g.8 uman ,e a%ior) ".2. #ou,le ,linding of a non*p armacologic treatment (e%eryone can see 5 o gets 5 at treatment8 if t e treatment if so o,%iously different8 e.g.8 type of %egeta,les)

30

)ommunity trial0

2opulatio n ?

2opulatio n -

O,ser%e Occurrence of #isease for ? !pecified 2eriod of 9ime /andomly ?ssign 9reatment Initiate 2rogram #o Jot ing

Measure Outcome

Measure Outcome

!ummary of community trials0 a. ?d%antages0 Only 5ay to directly estimate t e realistic impact of a c ange in ,e a%ior on t e incidence of disease ,. .imitations0 1. .ess control t an a clinical trial 2. Una,le to control for differences ,et5een communities 5it respect to 2.1. /acial composition 2.2. Education le%el 2.3. ?ge distri,ution 3. #ynamic population may lead to loss of demonstrated effect ". Jon*inter%ention influences (e.g.8 %olunteer groups8 media) can impact on ,ot control and treatment communities (SqC)

31

Unit 10. Causality Criteria for causality (IW8(q)0 to say one t ing is a causal factor to a disease8 t is factor must meet t e criteria0

temporal seKuence (temporality) =0 a. eFposures s ould precede t e e%ent. (0bzI) ,. t e onset (1) must occurred after t e induction (rl) latency period (Xs). c. .atency0 9 e period from disease initiation to manifestation. +ery often8 latency is t e term applied to t e time inter%al ,et5een eFposure and disease manifestation or recognition. d. Induction time0 9 e period from first eFposure to an agent or collection of agents to disease initiation. ZOften time referred to as .atency periodV Induction 2eriod >irst EFposure .atency 2eriod identification of disease

#isease Induced

.atency period is often used in cancer researc O 5 ile incu,ation time is usually applied in infectious diseases. 9 ey represent similar concept.

)onsistency (:+)0 a. a second condition t at supports a causal interpretation of an association is t e repeated o,ser%ation of t e association under different conditions of study. (IWbz C!"t2@) ,. in a %ariety of population8 e.g.8 %egeta,le can pre%ent colon cancer8 or garlic can reduce Y.. in t e ne5s c. in a %ariety of different types of studies d. ,y a %ariety of in%estigators Meta*analysis0 focus on contrasting and com,ining results from different studies8 in t e opes of identifying consistent patterns and sources of disagreement among t ose results.(uvo!"II8wx I;::+CIyY8z{o!"II'|vC L) Is a statistical analysis of a collection of studies8 especially an analysis in 5 ic studies are t e primary units of analysis. (nCq !"II867;}?oC!")

32

strengt of association () a. 9 e larger t e %alue of t e relati%e ris7 ()8 t e less li7ely t e association is to ,e spurious. (WK8IW; ,) ,iological gradient (2aGk~)Edose*response relations ip (b)0 a. #ose*response relations ip0 5 en t e eFposures ad increased t e ris7 also increase. (0k(k ) .inear 9 res old ()

< 9 res old 6 t e lo5est limit at 5 ic a stimulus ,ecome percepti,le. ,. >or dose8 5e a%e to consider its intensity(0)E concentration8 and duration (0'). c. in epi8 5e consider eFposure from t e en%ironment of its concentration (air sampling)8 or our of eFposureEor year of eFposure (for cancer)8 ,ut t e concentration can also from ,lood test. -lood test is most accurate8 ,ut 5it out t is luFury8 5e usually detect t e eFposure from ,reat ing air and our of 5or78 or location of 5or7 from t e contaminated sources.

!pecificity ()0 a. ? cause is ZspecificV to an effect if t e introduction of t e putati%e causal factor is follo5ed ,y t e occurrence of t e effect. (5 ene%er ? occurred8 t e disease occurred) E.g.8 infectious disease. (";$( ;:I (128W) ,. :o5e%er8 multiple causes and multiple effects are more often occurred. E.g.8 radiation eFposure may cause leu7emia8 cataracts8 t yroid cancer8 lung cancerY)8 smo7ing and as,estos from occupational eFposures can all cause lung cancer c. ?nd for c ronic disease8 it often caused ,y many factors8 e.g.8 genetic reasons and life styles.

,iological plausi,ility (2aVC)0 a. can ,e support ,y ,iological 7no5ledge8 not against 7no5ledge from la, eFperience. (;2aYZ*8nZI)

Unit 11. +aria,ility and -ias

33

!tatistical Measures of ?ssociation0 a. 1eneral0 1. 2*%alue0 9 e pro,a,ility t at t e difference ,et5een t e %alue of a %aria,le in your sample and t e true population %alue could a%e occurred ,y c ance alone 1.1. ? p*%alue of 0.0$ implies t at if t e same study 5as done 100 times8 t e difference o,ser%ed 5ould a%e occurred ,y c ance alone only $ times. 2. )onfidence Inter%al ()I) 6 ? measure of uncertainty a,out a parameter estimate (a mean8 O/8 //8 incidence rate8 etc) 2.1. Utility0 9 e 9$W confidence inter%al contains t e QtrueR population estimate 9$W of t e time. 2.2. 9ranslation0 If you sample 100 times8 t e 9$W)I 5ill contain t e true estimate 9$ times. 2.3. )I are a function of t e %aria,ility of t e data and t e sample siHe 3. )orrelation )oefficient r 6 ? Kuantitati%e measure of t e degree of linear association ,et5een %aria,les. 3.1. If r U 08 t e %aria,le are said to ,e posi%ely correlated 3.2. If r T 08 t e %aria,les are said to ,e negati%ely correlated. ?s @ increases8 A decreases8 or as @ decreases8 A increases. 3.3. If r I 08 t e %aria,le are said to ,e uncorrelated. 3.". 9 e p*%alue of a correlation coefficient depends only on t e magnitude of r and t e sample siHe n ". /egression analysis 6 ? statistical tool t at utiliHes t e relation ,et5een t5o or more Kuantitati%e %aria,les so t at one %aria,le can ,e predicted from t e ot er. ,. >or categorical %aria,les0 1. !imple group comparisons 2. Odds ratio8 relati%e ris78 and rate ratio 3. .ogistic regression models c. >or continuous %aria,les0 1. )orrection coefficient 2. /egression coefficient 3. 2artial correlation coefficients and multi%ariate models

3"

!tudy +alidity 1. Internal +alidity 2. EFternal +alidity !tudy -ias 1. !election ,ias 2. Information ,ias 3. )onfounding #efinition of )onfoundingn a. 9 e effect of an eFtraneous %aria,le t at 5 olly or partially accounts for t e apparent effect of t e study eFposure. (0!"I(<RRnq; Sq ) ,. )onfounder is a t ird %aria,le 5 ic may artificially create or mas7 an association ,et5een eFposure and disease.;0)YS( J<= I0)Y(W /eKuirements for confounders0 a. 9 e confounder must ,e associated 5it t e eFposure (0W) ,. 9 e confounder cannot ,e a conseKuence (pat 5ay) f t e eFposure (0( 'a) c. 9 e confounder must ,e a ris7 factor for t e disease (;:) )onfounder ?ssociation )ause

EFposure (ris7 factor)

)ause

#isease (outcome)

3$

Met ods for controlling confounding a. !tudy design 1. Eliminate t e factor 6 limit t e study group (o,tain omogeneity in t e sample) 2. /andomiHation 6 ?ttempting to insure t at eac group 5ill ,e eKually represented 5it confounding %aria,les (ma7e sure to c ec7 after randomiHation) 3. Matc ing 6 >orce t e proper distri,ution of confounders into groups ,. ?nalysis of pre%ious collected data 1. !tratificationE?nalysis of su,groups 1.1. )ompare eFposed and uneFposed groups 5it in narro5 ranges of t e confounder 1.2. #ecreases %aria,ility from t e confounder 2. !tandardiHation 2.1. Indirect standardiHation 2.1.1. Use a standard population to gi%e an eFpected num,er of cases ,y age and (sometimes) gender 2.1.2. 9 en calculate t e o,ser%ed cases in t e sample 2.1.3. 1enerate a standardiHed mortality ratio OEE 5 ic is independent of age differences 2.2. #irect standardiHation0 Use a standard population to calculate an age* ad4usted rate. .oo7 at percent of population ,y age categories and multiply ,y t e rate of disease in eac one. ?n age ad4usted num,er can ,e calculated. 3. ModelingEMulti%ariate analyses0 Use of a regression model to loo7 at effects of numerous %aria,les (eFposure and confounders) on a disease. 9 e independent effect of eFposure can ,e sorted out.

3&

Unit 12. !tudy )ritiKue

1. >ull reference #oes title reflect contentM Is t e a,stract sufficient to get a general idea of ,ac7ground8 purpose8 met ods8 results8 and conclusionM 2. Introduction a. /e%ie5 of t e literature 1. ?ppropriatenessErele%ance 2. )ompleteness ,. /ationale 1. Is t e rationale clear from t e introductionM c. :ypot esisEo,4ecti%e 1. )larity 2. .ogical association 5it literature re%ie5 and rationale 3. !tudy design and met ods a. #esign (o%erall o,4ecti%es8 le%el of measurement8 specific design) 1. = at are t ey trying to ac ie%eM 2. Ecological %ersus indi%idual le%el of measurement ,. 2opulation at ris7 1. 9arget population to 5 ic t e results s ould apply c. !ampling met od8 sample siHe8 selectionEeFclusion criteria for study group and comparison group 1. = at is t e study (source) populationM 2. )larity and appropriateness of sampling met od 3. !ufficiency of sample siHe ". ?ppropriateness and compara,ility of criteria applied to groups d. #ata sources 1. ?ppropriateness of dataE a,ility to reac o,4ecti%es 2. .imitations of data e. Et ical appro%al 1. =ere appropriate standards follo5ed8 o5 5ell is t is documentedM f. )onsent 1. = at 7ind of consent is appropriateM 2. = at 7ind of consent 5as o,tained (from 5 om8 o5)M g. #ependent %aria,le 1. = at are t e outcomes under studyM 2. :o5 are t ey defined and measuredM . Independent %aria,le(s) 1. = at are t e predictors8 ris7 factors under studyM 2. =o5 are t ey defined and measuredM i. )onfounders and effect modifiers 1. = at are t e potential or 7no5n confounders or effect modifiersM 2. :o5 are t ey defined and measuredM 3. :o5 are t ey dealt 5it in study design and analysisM 4. Information ,ias controlled ,y study design
3'

7.

l. m.

= at are t e strengt s and limitations of t e study design regarding to information ,ias ( o5 are data collected8 5 o pro%ides t e data8 training or ,linding met ods etc.) !election ,ias controlled ,y study design 1. = at are t e strengt s and limitations of t e study design regarding to selection ,iasM 2. :o5 5ell are t e selection met ods designed to capture a representati%e sample of t e target populationM 3. = at specific measures 5ere ta7en to maFimiHe participation among t ose selected for inclusionM Is met odology appropriate and used correctlyM ?re met ods descri,ed in sufficient detail to repeat t e 5or7 (data collection8 preparation and analysis)M

1.

". /esults a. Missing data 1. = at is t e eFtent and distri,ution of missing dataM 2. :o5 are missing data pre%entedM 3. :o5 are missing data dealt 5it M ,. Ma4or findings 1. = at are t e ma4or findings (only o5n results s ould ,e represented8 results from ot er researc s ould ,e in t e discussion.) 2. :o5 5ell do t ey relate to stated o,4ecti%es 3. :o5 5ell do t ey relate to t e met ods descri,ed c. )ontrol for confounding 1. :o5 5ell 5as confounding controlled in design and analysis 2. Is t ere li7ely to ,e residual confounding d. Is t e use of teFt and grap s to represent results appropriateM e. ?re numeric results andled appropriatelyM $. #iscussion and conclusion a. Internal %alidity 1. ?re t e results li7ely to ,e %alid (QtrueR) for t e study population ( a%e eFplanations ot er t an causal association ,een ruled out8 i.e. c ance occurrence and confounding) ,. EFternal %alidity 1. 1i%en t at t e results are internally %alid 6 are t ey li7ely to ,e eFternally %alid for ot er populationsM )an t e results ,e generaliHedM 9o 5 at populationsM c. )onsistency 5it ot er studies 1. ?re t e results and conclusions consistent 5it ot er studiesM 2. If not 6 5 at are t e li7ely eFplanations for t e inconsistencyM 3. #oes t e inconsistency diminis t e %alue of t e results or conclusionsM d. #o you agree 5it t e conclusion reac ed ,y t e aut orsM e. ?re t e aut ors conclusions clearly demarcated from t ose of ot ersM f. ?re t ere any Qnegati%eR findings t at t e aut ors a%e ignored in t eir interpretationM

3(

g. Is t e 5or7 of ot ers adeKuately considered and synt esiHed into t e current 5or7M . 9o 5 at eFtent do t e data support t e conclusions madeM 9o 5 at eFtent is Qguess5or7R in%ol%edM i. 9 eoretical importance 1. = at is t e t eoretical importance of t e study findingsM 9o 5 at eFtent does t e study contri,ute to our t eoretical 7no5ledge of t e issueM 4. 2ractical importance 1. 9o 5 at eFtent does t e study contri,ute to our practical 7no5ledge of t e issueM 2. ! ould 5e do somet ing differently in lig t of t e studyM 7. >urt er study 1. = at are t e Qmissing dataR in t e field of studyM 2. = at guidance does t e study pro%ide in terms of areas for furt er studyM &. /eferences and Ot er comments a. :o5 complete is t e list of referencesM ,. Is important referencesE7no5ledge missingM c. ?re statements included 5it out ,eing supported ,y referencesM d. ?re any references superfluousEunnecessaryM

39