Transparency in medicines evaluation: more openness is still required

Posted on 14 April 2009

By Agnes Vitry.
For decades, secrecy has surrounded the evaluation of new medicines by drug regulatory authorities. There are various reasons behind this tradition of regulatory secrecy (1). There are secrecy provisions in national regulations, often a lack of capacity and resources, confining bureaucratic routine and a certain inertia of medicine agencies. The main drive for secrecy however is the protection of “commercially confidential information”.

Nearly all early data on new medicines are acquired by pharmaceutical companies in industry-funded experimental studies and clinical trials. These data are then considered as trade secrets that need to be hidden from potential competitors.

This view is being challenged by consumer organisations and drug independent bulletins around the world [1, 2] because secrecy is a major obstacle to the development of knowledge about medicines and to the safe and effective use of medicines by consumers.

The importance of giving public access to medicines data has been shown repeatedly in recent years. In 2002 researchers uncovered that complete information available to the US Food and Drug Administration (FDA) on a new and highly promoted medicine, celecoxib, contradicted the conclusions of an article published in a major medical journal, the Journal of The American Medical Association (JAMA) [3, 4].

In 2005 a new antidiabetic drug, Muraglitazar, was recommended for approval by a FDA advisory committee. A research team conducted an independent analysis of the clinical trials that had been released under public disclosure laws. It found that the drug was associated with an excess incidence of serious adverse cardiovascular events and concluded that the agent should not be approved.

Muraglitazar development was consequently stopped in 2006. In 2008 an independent review of antidepressant trials registered with the FDA found that the trials producing negative results were less likely to be published [5]. This publication bias had led to an overestimation of the health benefits provided by antidepressants.

On several occasions, the US consumer advocacy group Public Citizen sued the FDA, under the Freedom of Information Act (FOIA) and obtained a broader access to medicines data kept by the FDA [2]. The Medicines in Europe Forum has been very active in reorienting European medicines policy towards public health and in advocating for greater transparency and free access to scientific data [6].

In 2004 a European Union directive (Directive 2004/27/EC) included new rules on transparency. European drug regulatory authorities are now required to make available in the public domain records of their meetings and decisions taken on marketing authorisations together with their assessment reports and underlying reasons for their judgments.

The directive requires that member states must ensure that members of staff of the competent authority responsible for granting authorisations, rapporteurs and experts concerned with the authorisation and surveillance of medicinal products have no financial or other interests in the pharmaceutical industry that could affect their impartiality.

Medicine agencies around the world provide differing levels of access to medicines information [7]. The US FDA is one of the most transparent regulatory agencies. However its disclosure policies still limit the public disclosure of data for many clinical trials on approved products as well as the release of the results of clinical trials undertaken to support supplemental new drug applications [8]. The transparency requirements of the 2004 European directive have been implemented only partially.

The European medicine agency has improved its processes, for example, concerning the provision of information on marketing applications that have been withdrawn [9]. However the EMEA refuses to communicate the Periodic Safety Update Reports which provide an update of the worldwide safety experience of a medicinal product at defined time points post-authorisation [10]. The EMEA also deletes important sections of documents including essential clinical and safety information.

Divergent national laws on freedom of information and a lack of clarity on what kinds of data can be disclosed may explain why many European agencies still do not provide full and timely access to medicines information [10, 11].

All information on drug safety and effectiveness that is submitted to regulatory authorities should be publicly available, including all pre-market laboratory and clinical data and post-marketing studies.

Commercial confidentiality’ cannot be a legitimate reason to withhold information on medicines that is relevant to the safety and well-being of patients. Transparency improves regulatory practices and ensures that regulatory agencies remain accountable to the public that they serve.

1. Health Action International. Statement of the International Working Group on Transparency and Accountability in Drug Regulation.  1996  [cited; Available from: www.haiweb.org/pubs/sec-sta.html.

2. Kesselheim, A.S. and M.M. Mello, Confidentiality laws and secrecy in medical research: improving public access to data on drug safety. Health Affairs, 2007. 26(2): p. 483-491.

3. Juni, P., A.W. Rutjes, and P.A. Dieppe, Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? BMJ, 2002. 324(7349): p. 1287-8.

4. Silverstein, F.E., et al., Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA, 2000. 284(10): p. 1247-55.

5. Turner, E.H., et al., Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med, 2008. 358(3): p. 252-60.

6. Prescrire Editorial Staff, Reorienting the course of medicines policy: actions are bearing fruit. Prescrire Int, 2003. 12(67): p. 192-4.

7. Vitry, A., et al., Provision of information on regulatory authorities' websites. Intern Med J, 2008.

8. Wood, A.J., Progress and deficiencies in the registration of clinical trials. N Engl J Med, 2009. 360(8): p. 824-30.

9. Vitry, A., V. Bertele, and S. Garattini, Drug regulation and the need for greater transparency. Regulatory Affairs Journal, 2009: p. 143-146.

10.    Personal communication, Prescrire 2009.

11.    Slijkerman, D., Transparency in EU regulatory agencies. 2009.