Published reports should inform the reader about all aspects of study design, conduct, analysis, and interpretation that are relevant for assessing the internal and external validity of the trial. The content and quality of trial reports in the literature, however, remain inconsistent on these points - this process is not perfect. The content of the medical literature reflects an imperfect editorial and peer review process. Despite the limitations of the peer review process, good alternatives currently do not exist for judging the merits of scientific papers.

Publication bias is the tendency for studies with “positive” findings to be preferentially selected for publication over those with “negative” findings, (i.e., it did not find a statistically significant result). If an editor has a choice of publishing a positive study and one with negative results, they may prefer publishing the positive results for various reasons. However, negative studies are very important and should be made known as well. For instance, early stopping a study of interferon gamma-1b when an interim analysis showed that patients with IPF did not benefit from the treatment is important imformation for other IPF patients who may have been prescribed interferon gamma-1b in off-label use and for others taking it for the conditions for which it already has approval (FDA Public Health Advisory on Interferon gamma-1b).

If the published literature is used as a basis for drawing conclusions about a treatment or a group of related treatments from independent studies, then an impression biased in favor of the treatment could result. Editors and referees are not the only ones to blame for the presence of publication bias. Investigators tend to lose enthusiasm for negative results because they may be viewed as less glamorous and even viewed as failures. This could lead to weaker reports, or even no reports, being submitted for publication. Journal editors and referees can reduce publication bias in two ways. First, they should assign greater weight to methodologic rigor and thorough reporting than to statistical significance. Second, they must be willing to report negative findings from sound studies with as much enthusiasm as positive reports.

Along with the efforts of individual journal editors to include negative trials, there have been recent public and private initiatives to increase public access to clinical trial results.

The U.S. NIH policy is that the results of its funded research should be available to the public.

We have already discovered that ClinicalTrials.gov provides updated information for locating U.S. government- and privately-supported clinical trials and results of certain completed trials. Observational studies addressing health issues in large groups of people or populations in natural settings are also included in the ClinicalTrials.gov database.

The site was developed by the U.S. National Institutes of Health (NIH), through its National Library of Medicine (NLM), in collaboration with the Food and Drug Administration (FDA), as a result of the FDA Modernization Act (1997). The types of trials required to be registered at the site expanded with the Food and Drug Administration Amendments Act of 2007. The "basic results" of trials that study drugs, biologics, or devices approved, licensed, or cleared by the FDA are now required to be posted in a timely manner. (read more about the registration requirements page and the clinical trials results page)

Many medical journals now have policies of only publishing a manuscript from a completed clinical trial if the trial has been registered at ClinicalTrials.gov.

Along with satisfying legislative requirements, pharmaceutical manufacturers are providing access to results from sponsored studies through various mechanisms. (e.g.GSK, Pfizer, Merck) as the Pharmaceutical Research and Manufacturers of America and the European Federation of Pharmaceutical Industries and Associations adopted joint Principles for Responsible Clinical Trial Data Sharing (2013).

Using the proper summary/descriptive statistics is essential. Although investigators may use standard deviations and standard errors interchangeably, the standard deviation is appropriate as a descriptive summary, whereas the standard error is intended to convey the uncertainty of an estimate (such as the mean). Confidence intervals are more informative than significance levels and p-values.

Reports of clinical trials usually do not distinguish between clinical significance and statistical significance - but they should. Clinical significance can be expressed in terms of the magnitude and direction of treatment effects or differences. Although this is important for superiority trials, it is even more important for equivalence and non-inferiority trials.

Some journals require structured titles and abstracts because they are the only part of many reports that some readers examine. Therefore, the abstract becomes very important - in the medical literature the abstract is critical. A good abstract for the report of a clinical trial includes objectives, design, setting or types of practices, characteristics of the study population, interventions used, primary outcome measurements, principal results, and conclusions. Abstracts should be no longer than 250 words and usually do not include descriptions of the statistical methods.

The reports for treatment mechanism and dose-finding studies (Phase I) should include information about study design, demographics, toxicity and side effects, and recommendations for later trials. The objectives of safety and efficacy studies (Phase II) are to demonstrate treatment feasibility, estimate treatment success, estimate treatment complications, and facilitate informal comparisons with other therapies that might motivate comparative trials.

With respect to the latter objective, the report should recognize the potential for strong selection bias and avoid overly-enthusiastic statements about relative efficacy. The reports for safety and efficacy studies should consist of the following outline:

• introduction
• objectives
• study design
• study setting
• demographics
• treatments
• outcome measures
• statistical methods
• results
• discussion and conclusions

The outline of reports for comparative efficacy trials (Phase III) is similar to that for safety and efficacy trials. There are many additional issues, however, to consider. For example, the reporting of treatment assignment (randomization) and masking procedures is necessary to assure readers about the internal validity of the trial. This is important because readers want to know how this was implemented. This is a mechanism that reviewers will use to assess the validity of the study.

The motivation and assumptions for the target sample size should be included, especially in a situation where the primary results are “negative” findings. The impact of various prognostic variables should be addressed with appropriate statistical analyses to demonstrate that treatment effects are not due entirely to them. Although the intent-to-treat principle should be followed in randomized trials, it is helpful to report on the results of various exploratory analyses as well.

Since the methods have direct implications on the validity of the results, top-line journals require thorough descriptions. They also expect supplemental reports. When the article is available online, there can be links to more detailed descriptions, figures, graphs, and tables.

In this lesson, among other things, we learned to:

• recognize critical elements in a journal article or abstract that reports clinical research
• apply CONSORT standards to reports of results from parallel group randomized trials and reports of safety
• access a vast number of trials registered with ClinicalTrials.gov