Understanding Clinical Studies: Obtaining Approval, Registering the Study, and Reporting the Results

Clinical studies typically involve human volunteers (also called participants) and are intended to advance medical knowledge and find better ways to prevent, screen for, diagnose, and/or treat disease. Each clinical study should have a protocol that describes what will be done in the study, how the study will be conducted, and why the individual parts of the study are necessary. A study may enroll volunteers with a particular disease or healthy people.

The goal of most clinical studies is to determine whether a new test or treatment is efficacious and safe. Clinical studies may also focus on other aspects of care, such as improving the quality of life for people who have chronic illnesses.

Types of Clinical Studies

Interventional vs. observational studies

In interventional studies, participants receive specific interventions according to the protocol created by the investigators. These interventions may be changes to participants' behavior, medical procedures, or medical products, such as drugs or devices.

The aim is to determine the safety and efficacy of the intervention by measuring certain outcomes in the participants. For example, investigators may give a drug or treatment to participants who have high blood pressure to see whether their blood pressure decreases.

In observational studies, participants may receive interventions or procedures as part of their routine medical care, but the participants are not assigned to specific interventions by the investigators (as in an interventional study). For example, investigators may observe a group of older adults to learn more about the effects of different lifestyles on cardiac health.

Prospective vs. retrospective studies

In a prospective study, the investigators watch for outcomes, such as the development of a disease, during the study period and relate this to other factors, such as suspected risk or protection factors. The study usually involves watching a cohort of subjects over a long period. The outcome of interest should be common in the study population; otherwise, the number of outcomes observed will be too small to be statistically meaningful.

All efforts should be made to avoid sources of bias, such as differential loss to follow-up. Prospective studies usually have fewer potential sources of bias and confounding than retrospective studies.

In a retrospective study, the investigators review existing data and examine exposures to suspected risk or protection factors in relation to an outcome that is established at the start of the study. Many valuable case-control studies, such as Lane and Claypon's 1926 investigation of risk factors for breast cancer, were retrospective investigations.

Confounding and bias are more common in retrospective studies than in prospective studies. For this reason, retrospective investigations are often criticized. If the outcome of interest is uncommon, the size of the prospective investigation required to estimate relative risk is often too large to be feasible, so a retrospective investigation must be performed. In retrospective studies, the odds ratio provides an estimate of relative risk.

Case-control vs. cohort studies

Case-control studies are those that compare patients who have a disease or outcome of interest (cases) with patients who do not have the disease or outcome (controls). In these studies, investigators look back retrospectively to compare how frequently the exposure to a risk factor is present in each group to determine the relationship between the risk factor and the disease.

The controls are selected on the basis of an unknown outcome. Case-control studies are usually good for studying rare outcomes. They are relatively inexpensive compared to cohort studies, as smaller numbers of participants are required, and they are quicker to complete. However, case-control studies are prone to selection bias and recall/retrospective bias.

Cohort studies are those in which one or more samples (called cohorts) are followed prospectively and subsequent status evaluations with respect to a disease or outcome are conducted to determine which initial exposure characteristics (risk factors) are associated with the disease or outcome. As the study is conducted, the outcome of participants in each cohort is measured and relationships with specific characteristics are determined.

These studies are usually (but not exclusively) prospective. They yield true incidence rates and relative risks, and unanticipated associations with outcome may be uncovered. Such studies are best for examining common outcomes. They are relatively expensive compared to case-control studies, as they require large numbers of participants and take a long time to complete. Cohort studies may be prone to attrition bias and bias associated with changes in methods over time.

How to Obtain Approval For and Register Your Clinical Study

Most clinical studies are reviewed, monitored, and approved by an institutional review board (IRB). IRBs are composed of physicians, statisticians, and members of the community. Their role is to make sure that the study is ethical, to protect the rights and welfare of the participants, and to ensure the risks are reasonable when compared to the potential benefits.

In the United States, a clinical trial must have IRB approval if a drug, biological product, or medical device regulated by the Food and Drug Administration (FDA) is being studied or if the trial is funded or carried out by the federal government.

As of July 1, 2005, the International Committee of Medical Journal Editors (ICMJE) requires that clinical trials must be registered before their results can be published. ClinicalTrials.gov, run by the United States National Library of Medicine (NLM), was the first online registry for clinical trials and is currently the largest and most widely used registry.

Clinical trial registration is important because it provides increased transparency and access to clinical trial results and protocols. Although ClinicalTrials.gov allows trials to be registered at any time during the study (after it has started, after completion of enrollment, or even after completion of the study), the ICMJE strictly requires that studies must be registered before or at the time of enrollment of the first patient (prospective registration). If a particular trial is not registered prospectively, it may not be publishable in any journal that follows ICMJE guidelines.

The World Health Organization has begun pushing for clinical trial registration with the initiation of the International Clinical Trials Registry Platform. There has also been action from the pharmaceutical industry, which released plans to make clinical trial data more transparent and publicly available. Released in October 2008, the revised Declaration of Helsinki states that "Every clinical trial must be registered in a publicly accessible database before recruitment of the first subject.”

Reporting the Results of Your Clinical Trial

Once published, your article will be read and critiqued by the scientific community. The data that you publish may contribute to systematic reviews, inform clinical guidelines, or influence clinical practice.

When reporting the results of your study, it is important to identify the appropriate reporting guideline. The Equator Network has developed a prototype decision tree that can help you choose the correct reporting guideline for your work.

In collaboration with Penelope Research, Equator has also developed an online application that can aid in the selection process. Note that this application only includes common reporting guidelines for generic study types and does not include most guideline extensions, which are used when non-standard trial methodologies are employed.

Reporting guidelines used for each main study type.

Study type: Reporting guidelines

Randomized trial: CONSORT

Observational study: STROBE

Systematic review: PRISMA

Case report: CARE

Qualitative research: SRQR, COREQ

Diagnostic/prognostic study: STARD, TRIPOD

Quality improvement study: SQUIRE

Economic evaluation: CHEERS

Animal pre-clinical study: ARRIVE

Study protocol: SPIRIT, PRISMA-P

Clinical practice guidelines: AGREE, RIGHT

(All links in this table obtained from http://www.equator-network.org/)