Dr.

Prachi Srivastava

Clinical study design is the formulation of trials and experiments in medical and epidemiological research, sometimes known as clinical trials. Many of the considerations here are shared under the more general topic of design of experiments but there can be others, in particular related to patient confidentiality and ethics.

Treatment studies
Randomized controlled trial
Double-blind randomized trial Single-blind randomized trial Non-blind trial

Nonrandomized trial (quasi-experiment)

Interrupted time series design (measures on a sample or a series of samples from the same population are obtained several times before and after a manipulated event or a naturally occurring event) - considered a type of quasi-experiment

Observational studies
Cohort study
Prospective cohort

Retrospective cohort
Time series study

Case-control study
Nested case-control study

Cross-sectional study
Community survey (a type of cross-sectional study)

Ecological study

 A randomized controlled trial (RCT) is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety (or more specifically, information about adverse drug reactions and adverse effects of other treatments) and efficacy or effectiveness of healthcare services (such as medicine or nursing) or health technologies (such as pharmaceuticals, medical devices or surgery). The terms "RCT" and randomized trial are often used synonymously, but some authors distinguish between "RCTs" which compare treatment groups with control groups not receiving treatment (as in a placebo-controlled study), and "randomized trials" which can compare multiple treatment groups with each other. The key distinguishing feature of the usual RCT is that study subjects, after assessment of eligibility and recruitment, but before the intervention to be studied begins, are randomly allocated to receive one or other of the alternative treatments under study. Random allocation in real trials is complex, but conceptually, the process is like tossing a coin. After randomization, the two (or more) groups of subjects are followed up in exactly the same way, and the only differences between the care they receive, for example, in terms of procedures, tests, outpatient visits, follow-up calls etc. should be those intrinsic to the treatments being compared.

 The most important advantage of proper randomization is that it minimizes allocation bias, balancing both known and unknown prognostic factors, in the assignment of treatments. An RCT may be Blinded, (also called "masked") by "procedures that prevent study participants, caregivers, or outcome assessors from knowing which intervention was received." Unlike allocation concealment, blinding is sometimes inappropriate or impossible to perform in an RCT; for example, if an RCT involves a treatment in which active participation of the patient is necessary (e.g., physical therapy), participants cannot be blinded to the intervention. Traditionally, blinded RCTs have been classified as "single-blind," "double-blind," or "triple-blind"; however, in 2001 and 2006 two studies showed that these terms have different meanings for different people. The 2010 CONSORT Statement specifies that authors and editors should not use the terms "single-blind," "doubleblind," and "triple-blind"; instead, reports of blinded RCT should discuss "If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how." RCTs without blinding are referred to as "unblinded", "open", or (if the intervention is a medication) "open-label". In 2008 a study concluded that the results of unblinded RCTs tended to be biased toward beneficial effects only if the RCTs' outcomes were subjective as opposed to objective.

 A cohort study or panel study is a form of longitudinal study (a type of observational study) used in medicine, social science, actuarial science, and ecology. It is an analysis of risk factors and follows a group of people who do not have the disease, and uses correlations to determine the absolute risk of subject contraction. It is one type of clinical study design and should be compared with a cross-sectional study. Cohort studies are largely about the life histories of segments of populations, and the individual people who constitute these segments. A cohort is a group of people who share a common characteristic or experience within a defined period (e.g., are born, are exposed to a drug or a vaccine, etc.). Cohort studies can either be conducted prospectively, or retrospectively from archived records. A cohort study is often undertaken to obtain evidence to try to refute the existence of a suspected association between cause and effect; failure to refute a hypothesis strengthens confidence in it. Crucially, the cohort is identified before the appearance of the disease under investigation. The study groups follow a group of people who do not have the disease for a period of time and see who develops the disease (new incidence).

 A Cohort Study is a study in which subjects who presently have a certain condition and/or receive a particular treatment are followed over time and compared with another group who are not affected by the condition under investigation. For research purposes, a cohort is any group of individuals who are linked in some way or who have experienced the same significant life event within a given period. There are many kinds of cohorts, including birth (for example, all those who born between 1970 and 1975) disease, education, employment, family formation, etc. Any study in which there are measures of some characteristic of one or more cohorts at two or more points in time is cohort analysis.

Prospective Study
A prospective cohort study is a cohort study that follows over time a group of similar individuals (cohorts) who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome. For example, one might follow a cohort of middle-aged truck drivers who vary in terms of smoking habits, to test the hypothesis that the 20-year incidence rate of lung cancer will be highest among heavy smokers, followed by moderate smokers, and then nonsmokers. The prospective study is important for research on the etiology of diseases and disorders in humans because for ethical reasons people cannot be deliberately exposed to suspected risk factors in controlled experiments. Prospective cohort studies are typically ranked higher in the hierarchy of evidence than retrospective cohort studies. It can be more expensive than a casecontrol study. One of the advantages of prospective cohort studies is they can help determine risk factors for being infected with a new disease because they are a longitudinal observation over time, and the collection of results is at regular time intervals, so recall error is minimized.

 prospective study, an analytic study designed to determine the relationship between a condition and a characteristic shared by some members of a group. The population selected is healthy at the beginning of the study. Some of the members of the group share a particular characteristic, such as cigarette smoking. The researcher follows the population group over a period of time, noting the rate at which a condition, such as lung cancer, occurs in the smokers and in the nonsmokers. A prospective study may involve many variables or only two; it may seek to demonstrate a relationship that is an association or one that is causal. Prospective studies produce a direct measure of risk called the relative risk. Compare retrospective study.
Mosby's Medical Dictionary, 8th edition. 2009, Elsevier.

 In statistics, signal processing, econometrics and mathematical finance, a time series is a sequence of data points, measured typically at successive times spaced at uniform time intervals. Time series analysis comprises methods for analyzing time series data in order to extract meaningful statistics and other characteristics of the data. Time series forecasting is the use of a model to forecast future events based on known past events to predict data points before they are measured. Time series are very frequently plotted via line charts. Time series data have a natural temporal ordering. This makes time series analysis distinct from other common data analysis problems, in which there is no natural ordering of the observations (e.g. explaining people's wages by reference to their education level, where the individuals' data could be entered in any order). Time series analysis is also distinct from spatial data analysis where the observations typically relate to geographical locations (e.g. accounting for house prices by the location as well as the intrinsic characteristics of the houses). A time series model will generally reflect the fact that observations close together in time will be more closely related than observations further apart. In addition, time series models will often make use of the natural one-way ordering of time so that values for a given period will be expressed as deriving in some way from past values, rather than from future values.

 A case-control study is a type of study design in epidemiology. Case-control studies are used to identify factors that may contribute to a medical condition by comparing subjects who have that condition (the 'cases') with patients who do not have the condition but are otherwise similar Case-control studies are a relatively inexpensive and frequently-used type of epidemiological study that can be carried out by small teams or individual researchers in single facilities in a way that more structured experimental studies often cannot be. They have pointed the way to a number of important discoveries and advances. The great triumph of the case-control study was the demonstration of the link between tobacco smoking and lung cancer, by Sir Richard Doll and others after him. Opponents argued for many years that this type of study cannot prove causation, but the eventual results of cohort studies confirmed the causal link which the casecontrol studies suggested, and it is now accepted that tobacco smoking is the cause of about 87% of all lung cancer mortality in the US.

 In a nested case-control study, cases of a disease that occur in a defined cohort are identified and, for each, a specified number of matched controls is selected from among those in the cohort who have not developed the disease by the time of disease occurrence in the case.

For many research questions, the nested case-control design potentially offers impressive reductions in costs and efforts of data collection and analysis compared with the full cohort approach, with relatively minor loss in statistical efficiency (see restricted randomization).
The nested case-control design is particularly advantageous for studies of biologic precursors of disease. Compared with case-control studies, nested case-control studies can reduce 'recall bias' and temporal ambiguity, and compared with cohort studies can reduce cost and save time. The drawback of nested case-control studies is non-diseased persons from whom the controls are selected may not be fully representative of the original cohort, due to death or failure to follow-up cases.

 Cross-sectional studies (also known as Cross-sectional analysis) form a class of research methods that involve observation of all of a population, or a representative subset, at a defined time. They differ from case-control studies in that they aim to provide data on the entire population under study, whereas case-control studies typically include only individuals with a specific characteristic, with a sample, often a tiny minority, of the rest of the population. Both are a type of observational study. Unlike case-control studies, they can be used to describe absolute risks and not only relative risks. They may be used to describe some feature of the population, such as prevalence of an illness, or they may support inferences of cause and effect. Cross-sectional studies involve data collected at a defined time. They are often used to assess the prevalence of acute or chronic conditions, or to answer questions about the causes of disease or the results of medical intervention. They may also be described as censuses. Cross-sectional studies may involve special data collection, including questions about the past, but they often rely on data originally collected for other purposes. It is moderately expensive, not suitable for rare diseases. Difficulty in recalling past events may also contribute bias.

 An ecological study is an epidemiological study in which the unit of analysis is a population rather than an individual. For instance, an ecological study may look at the association between smoking and lung cancer deaths in different countries. An ecological study is normally regarded as inferior to non-ecological designs such as cohort and case-control studies because it is susceptible to the ecological fallacy. An example of an ecological study is the analysis of the effects of disinfection byproducts on newborn babies, using 109 Massachusetts towns as units of analysis. Ecological studies can be easily confused with cohort studies, especially if different cohorts are located in different places. The difference is that in the case of ecological studies there is no information available about the individual members of the populations compared (e.g. comparing several states based on state-wide average air pollution and state-wide average prevalence of respiratory diseases); whereas in a cohort study the data pair exposure/health is known for each individual.

 In spite of their weaknesses, ecological studies are useful because they can be carried out easily, quickly and inexpensively using data that are generally already available. If interesting and strong associations are observed, the results of ecological studies can provide the opportunity for later, more carefully designed studies (though more expensive and time-consuming) to build on the initial observations.