Drazen transparency for clinical trials -- the test act


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Drazen transparency for clinical trials -- the test act

  1. 1. The n e w e ng l a n d j o u r na l of m e dic i n e edi t or i a l Transparency for Clinical Trials — The TEST Act Jeffrey M. Drazen, M.D.In the past few years, registration of clinical trials (i.e., making no distinction between trials ofin a publicly accessible database has become approved vs. unapproved products); requiring allroutine. In the United States, much of the impe- foreign trials that are used to support market-tus for registration derives from the Food and ing in the United States to be registered; man-Drug Administration Amendments Act of 2007 dating results reporting for all trials within 2 years(FDAAA). As a result of this law and other ac- after study completion (including trials of unap-tions,1,2 most interventional clinical trials con- proved drugs or devices); and extending resultsducted in the United States have been registered reporting to include the deposition of consentat ClinicalTrials.gov, where, in most cases, the and protocol documents approved by institu-trial results must also be reported. The curators tional review boards.of the database have designed a simple tabular This legislation is important. The bill requiresformat in which the characteristics of the partici- that any trial that could be used to support anpants enrolled are reported in one table, the key application for FDA approval be registered inprimary and secondary outcomes in a second ClinicalTrials.gov and that the results be reportedtable, and adverse events in a third table. Journals in a timely fashion. It requires that early-phaseadhering to the International Committee of Med- trials (those in which a drug is initially tested inical Journal Editors guidance for manuscripts humans) be registered. Thus, these trials willsubmitted to biomedical journals3 have made it become public knowledge.clear that reporting results in this fashion will The bill also requires that results be reportednot be considered prepublication of submitted whether the drug is submitted for FDA approvalmanuscripts.4 One of the purposes of trial regis- by the manufacturer or not. For example, in atration is to provide a third-party storehouse of case in which a novel therapeutic strategy is as-trial designs and results. However, for this re- sociated with adverse outcomes, informationsource to be of value, it is important that the en- about these outcomes would be in the database,tire portfolio of clinical trials be in the database. even if the product were subsequently abandoned But there are loopholes in FDAAA that have by the manufacturer. That way, if another entitymade it possible for some entities to conduct pursued the same treatment approach with aclinical trials without registering them or re- different intervention, the trial designers wouldporting the results. On August 2, 2012, Repre- be aware of the potential dangers and could de-sentative Edward Markey (D-MA) introduced into velop means for monitoring and mitigating thethe U.S. Congress the Trial and Experimental potential toxic effects.Studies Transparency (TEST) Act (H.R. 6272) to Consider the disastrous results obtained whenclose these loopholes. The TEST Act expands re- studies were conducted with an anti-CD28 anti-porting requirements under existing federal law body.5 All the healthy volunteers injected withby broadening the scope to include all interven- the agent fell ill, some gravely ill, within minutestional studies of drugs or devices, regardless of after receiving the treatment. Given that thisphase (i.e., including phase 1), design (i.e., in- trial did not need to be registered in a publiccluding single-group trials), or approval status database, would the data have become public n engl j med  nejm.org 1 The New England Journal of Medicine Downloaded from nejm.org by MARILYN MANN on August 20, 2012. For personal use only. No other uses without permission. Copyright © 2012 Massachusetts Medical Society. All rights reserved.
  2. 2. editorial knowledge if the volunteers had not been admit- clinical trials should be conducted in the open, ted to a public hospital? By requiring both regis- with full public knowledge of the question asked, tration and results reporting, the government the intervention tested, and the results obtained. would ensure that the data accrued became part The TEST Act is another step toward this end, of the public record and could guide further and we strongly support it. work in a given area. Disclosure forms provided by the author are available with the Another provision of the TEST Act would re- full text of this article at NEJM.org. quire that trials conducted outside the United This article was published on August 8, 2012, at NEJM.org. States, but used to support an application to the FDA, be registered and that their results be re- 1. De Angelis C, Drazen JM, Frizelle FA, et al. Clinical trial ported in the database in a timely fashion. This registration: a statement from the International Committee of Medical Journal Editors. N Engl J Med 2004;351:1250-1. provision would ensure that the participants 2. International Clinical Trials Registry Platform (http://www who put themselves at risk to test new treat- .who.int/ictrp/en). ments see the fruits of their altruism in the 3. Uniform requirements for manuscripts submitted to bio- medical journals (http://www.icmje.org/urm_main.html). public domain. Simply put, a trial could be 4. Laine C, Horton R, DeAngelis CD, et al. Clinical trial regis- moved offshore but could not be hidden. tration — looking back and moving ahead. N Engl J Med 2007; We can make progress in medicine only if 356:2734-6. 5. Suntharalingam G, Perry MR, Ward S, et al. Cytokine storm people are willing to put themselves at risk to in a phase 1 trial of the anti-CD28 monoclonal antibody test new diagnostic and therapeutic approaches. TGN1412. N Engl J Med 2006;355:1018-28. To recognize and reward these participants, and DOI: 10.1056/NEJMe1209433 in keeping with the Declaration of Helsinki, Copyright © 2012 Massachusetts Medical Society.2 n engl j med  nejm.org The New England Journal of Medicine Downloaded from nejm.org by MARILYN MANN on August 20, 2012. For personal use only. No other uses without permission. Copyright © 2012 Massachusetts Medical Society. All rights reserved.