A Taxpayer-Funded Clinical Trial Registry Exists!

A Taxpayer-Funded Clinical Trial Registry Exists!

Thu, 6 Oct 2005

A former FDA medical officer reports: A Taxpayer-Funded Clinical Trials Registry and Results Database: It already exists within the US Food and Drug Administration.

But the agency keeps the vital information about drug safety secret and inaccessible.

So, all the while that clinical trial analysts, (more recently) journal editors, patient advocates, and members of Congress have been calling for registries, Dr. Erick Turner reported in December 2004, that FDA officials have kept silent about the existing registry consisting of ALL new drug applications (NDAs) that the agency maintains at public expense.

Dr. Turner sheds light on the agency’s duplicity and the inadequacy of various other existing registries, including ClinialTrials.gov, the registry mandated by Congress under the FDA Modernization Act, 1997. ClinicalTrials.gov “appears not to be comprehensive. A study found that, of 127 cancer protocols sponsored by pharmaceutical companies that met criteria for inclusion, only 48% were in fact submitted to the registry [1].” Dr. Turner points out that voluntary, discretionary registries “one can check a number of registries and still have little assurance that all the relevant trials of interest have been included.”

And he explains what the unique features of the FDA NDA registry are:

First: “Before a pharmaceutical company can conduct a US trial that it intends to use in support of a new drug application (NDA), it must first register that trial with the FDA. Because the NDA forms the basis for marketing approval, it seems likely that the percentage of industry-sponsored trials that are registered with the FDA is very high. This registration takes the form of an investigational new drug (IND) application [2]. The IND contains a trial protocol; protocols for additional studies within the same clinical trials program are submitted as amendments to the IND. Later, when the sponsor has completed its clinical trials program and wishes to apply for marketing approval, it submits its NDA.”

Second: “The FDA then begins the NDA review process, during which a physician, a statistician, and a pharmacologist, among others, generate lengthy review documents [3]. These reviews not only address the sponsor’s analyses of the data on pivotal studies, but they often also include reanalyses by the reviewers using raw data obtained from the sponsor. These analyses are conducted in adherence to the statistical methods set forth a priori in the original trial protocols. (By contrast, with most journal publications, it is usually not possible for the reader to verify whether what is presented as the main finding is consistent with the original hypothesis or whether it was a post hoc finding.)”

Third: “having access to the FDA review documents allows us to become aware of, and see beyond, apparent publication bias. It is in the best interest of the public health for the FDA to make as many reviews available as possible. According to the FDA Web site, "As FDA continues to be one of the world’s leading agencies in its emphasis on openness and transparency, it is aware that making even more information available to the public will further the Agency’s mission to protect and promote public health and improve its credibility. For example, FDA has aggressively implemented the Electronic Freedom of Information Act…" [11].

By contrast, “the availability of review documents on Drugs@FDA is sporadic. To take additional examples from psychiatry, NDA reviews have been posted on Drugs@FDA for  some approved drug-indication combinations, such as fluoxetine for pediatric depression, and aripiprazole and quetiapine for schizophrenia. However, NDA reviews for many other drug-indication combinations have not been posted: the Prozac Weekly formulation of fluoxetine, clozapine for suicidal behavior in patients with schizophrenia or schizoaffective disorder, and quetiapine for mania, among others. A review on paroxetine for pediatric depression, the subject of Elliot Spitzer’s suit against GlaxoSmithKline, is not posted.”

So why has FDA’s NDA clinical trial registry not been mentioned by FDA officials when asked at a Congressional hearing whether the FDA intended to support various proposals to create centralized registries and databases that would duplicate FDA’s registry. Janet Woodcock, FDA’s acting deputy commissioner for operations, said, “I strongly support the goal of transparency and availability of information on human subjects,” noting disingenuously that the agency was contributing to ClinicalTrials.gov. When asked whether negative data would be included, Woodcock said the agency is prevented from disclosing certain trial information by “legal restraints.” Woodcocck falsely stated: “We can’t compel companies to reveal” negative trial data. When Congressional committee members repeatedly demanded that she cite the rules preventing that disclosure,  Woodcock demurred, saying she could provide the statutes at a later date. See: Alicia Ault. House berates FDA, drug makers: US Congressional subcommittee holds hearing on clinical trial disclosure rules. the SCIENTIST. Sep. 10, 2004 at: http://www.the-scientist.com/news/20040910/04

Could it be that like Moliere’s Bourgeois Gentleman, who was astonished to learn he had been speaking prose for 40 years, Dr. Janet Woodcock who heads FDA’s Center for Drug Evaluation was unaware that the FDA maintains the most comprehensive clinical trial registry whose data–if it were accessible–could saves lives ?

Dr. Erick Turner, a psychiatrist and pharmacologist who reviewed psychotropic drugs at the FDA, and has extensive experience analyzing clinical trial data for pharmaceutical companies, is now  the medical director of the Mood Disorders Program at the Portland Veteran Affairs Medical Center, and a professor of psychiatry and pharmacology /physiology at Oregon Health and Science University.

References cited from Dr. Turner’s article:

1. Derbis J, Toigo T, Woods J, Evelyn B, Banks D (2003) FDAMA section 113: Information program on clinical trials for serious and life-threatening diseases [poster]. Ninth Annual FDA Science Forum; 2003 April 24; Washington, D. C.

2. Center for Drug Evaluation and Research (2004) Investigational new drug (IND)  application process. Food and Drug Administration. Available: http://www.fda.gov/ cder/regulatory/applications/ind_page_1.htm.

3. Center for Drug Evaluation and Research (2004) NDA review process. Food and Drug Administration. Available: http://www.fda. gov/cder/handbook/nda.htm.

Entire article available free of charge at PLoS Biology, a peer reviewed, open access medical journal: A Taxpayer-Funded Clinical Trials Registry and Results Database It already exists within the US Food and Drug Administration at: http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0010060

Contact: Vera Hassner Sharav
212-595-8974