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Dr. Prachi Srivastava

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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 beothers, in particular related to patient confidentiality and ethics.

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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 ofsamples from the same population are obtained several times before andafter a manipulated event or a naturally occurring event) - considered atype of quasi-experiment

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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

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A randomized controlled trial (RCT) is a type of scientific experiment - a form ofclinical 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) orhealth 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 controlgroups not receiving treatment (as in a placebo-controlled study), and "randomizedtrials" which can compare multiple treatment groups with each other.

The key distinguishing feature of the usual RCT is that study subjects, afterassessment of eligibility and recruitment, but before the intervention to be studied

begins, are randomly allocated to receive one or other of the alternative treatmentsunder study.

Random allocation in real trials is complex, but conceptually, the process is liketossing a coin. After randomization, the two (or more) groups of subjects arefollowed up in exactly the same way, and the only differences between the care theyreceive, for example, in terms of procedures, tests, outpatient visits, follow-up calls

etc. should be those intrinsic to the treatments being compared.

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The most important advantage of proper randomization is that it minimizesallocation bias, balancing both known and unknown prognostic factors, in theassignment of treatments.

An RCT may be Blinded, (also called "masked") by "procedures that prevent studyparticipants, caregivers, or outcome assessors from knowing which interventionwas received." Unlike allocation concealment, blinding is sometimes inappropriateor impossible to perform in an RCT; for example, if an RCT involves a treatment inwhich 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 termshave different meanings for different people. The 2010 CONSORT Statementspecifies that authors and editors should not use the terms "single-blind," "double-blind," 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 interventionis a medication) "open-label". In 2008 a study concluded that the results ofunblinded RCTs tended to be biased toward beneficial effects only if the RCTs'outcomes were subjective as opposed to objective.

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A cohort study or panel study is a form of longitudinal study (a type of observationalstudy) 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 thedisease, and uses correlations to determine the absolute risk of subject contraction. It isone 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 adefined period (e.g., are born, are exposed to a drug or a vaccine, etc.).

Cohort studies can either be conducted prospectively, or retrospectively from archivedrecords.

A cohort study is often undertaken to obtain evidence to try to refute the existence of asuspected association between cause and effect; failure to refute a hypothesis strengthensconfidence in it. Crucially, the cohort is identified before the appearance of the diseaseunder investigation. The study groups follow a group of people who do not have thedisease for a period of time and see who develops the disease (new incidence).

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A Cohort Study is a study in which subjects who presentlyhave 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. Anystudy in which there are measures of some characteristic of

one or more cohorts at two or more points in time is cohort

analysis.

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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 affectrates of a certain outcome.

For example, one might follow a cohort of middle-aged truck drivers who vary in terms of smokinghabits, to test the hypothesis that the 20-year incidence rate of lung cancer will be highest amongheavy smokers, followed by moderate smokers, and then nonsmokers.

The prospective study is important for research on the etiology of diseases and disorders in humansbecause for ethical reasons people cannot be deliberately exposed to suspected risk factors incontrolled experiments.

Prospective cohort studies are typically ranked higher in the hierarchy of evidence than retrospectivecohort 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 beinginfected 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

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prospective study, an analytic study designed todetermine the relationship between a condition and acharacteristic shared by some members of a group. Thepopulation selected is healthy at the beginning of the study.Some of the members of the group share a particularcharacteristic, such as cigarette smoking. The researcherfollows the population group over a period of time, notingthe rate at which a condition, such as lung cancer, occursin the smokers and in the nonsmokers. A prospective studymay involve many variables or only two; it may seek todemonstrate a relationship that is an association or onethat is causal. Prospective studies produce a direct

measure of risk called the relative risk. Compareretrospective study.

Mosby's Medical Dictionary, 8th edition. 2009, Elsevier.

http://medical-dictionary.thefreedictionary.com/relative+riskhttp://medical-dictionary.thefreedictionary.com/retrospective+studyhttp://medical-dictionary.thefreedictionary.com/retrospective+studyhttp://medical-dictionary.thefreedictionary.com/relative+risk

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In statistics, signal processing, econometrics and mathematical finance, a time series is asequence of data points, measured typically at successive times spaced at uniform timeintervals.

Time series analysis comprises methods for analyzing time series data in order to extractmeaningful statistics and other characteristics of the data. Time series forecasting is theuse of a model to forecast future events based on known past events to predict datapoints 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 orderingof 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 observationstypically relate to geographical locations (e.g. accounting for house prices by thelocation as well as the intrinsic characteristics of the houses).

A time series model will generally reflect the fact that observations close together intime will be more closely related than observations further apart. In addition, time seriesmodels will often make use of the natural one-way ordering of time so that values for agiven period will be expressed as deriving in some way from past values, rather thanfrom future values.

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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 comparingsubjects who have that condition (the 'cases') with patients who do not have thecondition but are otherwise similar

Case-control studies are a relatively inexpensive and frequently-used type ofepidemiological study that can be carried out by small teams or individualresearchers in single facilities in a way that more structured experimental studies

often cannot be. They have pointed the way to a number of important discoveriesand advances.

The great triumph of the case-control study was the demonstration of the linkbetween tobacco smoking and lung cancer, by Sir Richard Doll and others afterhim.

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 case-control studies suggested, and it is now accepted that tobacco smoking is the causeof about 87% of all lung cancer mortality in the US.

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

For many research questions, the nested case-control design potentially offers impressivereductions in costs and efforts of data collection and analysis compared with the fullcohort approach, with relatively minor loss in statistical efficiency (see restrictedrandomization).

The nested case-control design is particularly advantageous for studies of biologicprecursors 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 savetime.

The drawback of nested case-control studies is non-diseased persons from whom thecontrols are selected may not be fully representative of the original cohort, due to deathor failure to follow-up cases.

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Cross-sectional studies (also known as Cross-sectional analysis) form a class ofresearch methods that involve observation of all of a population, or a representativesubset, at a defined time.

They differ from case-control studies in that they aim to provide data on the entirepopulation under study, whereas case-control studies typically include onlyindividuals with a specific characteristic, with a sample, often a tiny minority, of therest of the population. Both are a type of observational study.

Unlike case-control studies, they can be used to describe absolute risks and not onlyrelative risks. They may be used to describe some feature of the population, such asprevalence 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 usedto assess the prevalence of acute or chronic conditions, or to answer questions aboutthe causes of disease or the results of medical intervention.

They may also be described as censuses. Cross-sectional studies may involvespecial data collection, including questions about the past, but they often rely ondata originally collected for other purposes. It is moderately expensive, not suitablefor rare diseases. Difficulty in recalling past events may also contribute bias.

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An ecological study is an epidemiological study in which the unit of

analysis is a population rather than an individual. For instance, anecological study may look at the association between smoking and lungcancer deaths in different countries.

An ecological study is normally regarded as inferior to non-ecologicaldesigns such as cohort and case-control studies because it is susceptible to

the ecological fallacy. An example of an ecological study is the analysis ofthe effects of disinfection byproducts on newborn babies, using 109Massachusetts towns as units of analysis.

Ecological studies can be easily confused with cohort studies, especially ifdifferent cohorts are located in different places.

The difference is that in the case of ecological studies there is noinformation available about the individual members of the populationscompared (e.g. comparing several states based on state-wide average airpollution and state-wide average prevalence of respiratory diseases);whereas in a cohort study the data pair exposure/health is known for each

individual.

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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.

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