Transparency for clinical trials--the TEST Act.

In the past few years, registration of clinical trials in a publicly accessible database has become routine. In the United States, much of the impetus for registration derives from the Food and Drug Administration Amendments Act of 2007 (FDAAA). As a result of this law and other actions,1,2 most interventional clinical trials conducted in the United States have been registered at ClinicalTrials.gov, where, in most cases, the trial results must also be reported. The curators of the database have designed a simple tabular format in which the characteristics of the participants enrolled are reported in one table, the key primary and secondary outcomes in a second table, and adverse events in a third table. Journals adhering to the International Committee of Medical Journal Editors guidance for manuscripts submitted to biomedical journals3 have made it clear that reporting results in this fashion will not be considered prepublication of submitted manuscripts.4 One of the purposes of trial registration is to provide a third-party storehouse of trial designs and results. However, for this resource to be of value, it is important that the entire portfolio of clinical trials be in the database. But there are loopholes in FDAAA that have made it possible for some entities to conduct clinical trials without registering them or reporting the results. On August 2, 2012, Representative Edward Markey (D-MA) introduced into the U.S. Congress the Trial and Experimental Studies Transparency (TEST) Act (H.R. 6272) to close these loopholes. The TEST Act expands reporting requirements under existing federal law by broadening the scope to include all interventional studies of drugs or devices, regardless of phase (i.e., including phase 1), design (i.e., including single-group trials), or approval status (i.e., making no distinction between trials of approved vs. unapproved products); requiring all foreign trials that are used to support marketing in the United States to be registered; mandating results reporting for all trials within 2 years after study completion (including trials of unapproved drugs or devices); and extending results reporting to include the deposition of consent and protocol documents approved by institutional review boards. This legislation is important. The bill requires that any trial that could be used to support an application for FDA approval be registered in ClinicalTrials.gov and that the results be reported in a timely fashion. It requires that early-phase trials (those in which a drug is initially tested in humans) be registered. Thus, these trials will become public knowledge. The bill also requires that results be reported whether the drug is submitted for FDA approval by the manufacturer or not. For example, in a case in which a novel therapeutic strategy is associated with adverse outcomes, information about these outcomes would be in the database, even if the product were subsequently abandoned by the manufacturer. That way, if another entity pursued the same treatment approach with a different intervention, the trial designers would be aware of the potential dangers and could develop means for monitoring and mitigating the potential toxic effects. Consider the disastrous results obtained when studies were conducted with an anti-CD28 antibody.5 All the healthy volunteers injected with the agent fell ill, some gravely ill, within minutes after receiving the treatment. Given that this trial did not need to be registered in a public database, would the data have become public