Introduction

Lawmakers and members of the public, healthcare industry, and pharmaceutical industry have all voiced the need for greater transparency in clinical research in order to provide optimal protection of and benefit to patients. In addition to reporting trial results on the US clinical trial registry ClinicalTrials.gov, the sponsor (the organization or individual[s] funding the trial) or investigator (the physician conducting the trial) of an applicable clinical trial must also provide certain protocol information, giving viewers the opportunity to accurately interpret results. However, controversy exists regarding just how much protocol information should be made publicly available.

Background

The Food and Drug Administration Amendments Act of 2007 (FDAAA) requires registration and reporting of basic results on ClinicalTrials.gov for all clinical trials of pharmaceutical drugs and medical devices subject to regulation by the US Food and Drug Administration (FDA).  In an effort to make more clinical trial information available to the public, the Trial and Experimental Studies Transparency Act of 2012 (TEST Act) proposes several additional reporting requirements, including mandatory publication of the full trial protocol and all amendments to the protocol. Rules under the FDAAA are somewhat less stringent, requiring publication only of “such information on the protocol…as may be necessary to help evaluate the results of the trial.”

Issue

Should investigators/sponsors of registered clinical trials be required to provide the full trial protocol for public access on ClinicalTrials.gov?

Rule

The full protocol should be provided for public access on ClinicalTrials.gov only if the following conditions are satisfied:

1. Patient populations can reasonably expect to benefit from increased accessibility to methodological data.

2. The proposed policy will not negatively influence scientific innovation, whether by means of affecting market competition or otherwise.

Analysis

Recent studies suggest that the current amount of protocol information required to be reported on ClinicalTrials.gov is inadequate to assess the risk of bias in clinical trials. Reveiz et al. looked at reported protocol information for clinical trials on ClinicalTrials.gov following passage of the FDAAA. The researchers analyzed the protocols for information determined to influence bias in clinical trials. The study found overall poor reporting of such information; for instance, only 65% of trials adequately reported primary outcomes of the trial, and just 8% of RCTs (excluding open label trials) adequately reported blinding procedures. For trials that compare two or more treatments, blinding procedures prevent certain people involved in the trial (e.g., patients and/or doctors) from knowing which type of treatment the patient is receiving. Dal-Ré et al. also found deficiencies in the current protocol reporting requirements, specifically with regard to methods relevant to recruitment of patients and healthy volunteers for participation in clinical trials.

However, by making the full protocol document publicly available, pharmaceutical companies may run the risk of disclosing proprietary information (also known as “trade secrets”). Peer-reviewed journals, including the Journal of Clinical Oncology, often provide redactions of protocols for public view, rather than the complete document, for this reason. A recommendation report from medical journal and pharmaceutical industry professionals suggests making more complete protocol information available to the public but acknowledges the need for protection of proprietary information within the pharmaceutical industry. A spokesperson for the Pharmaceutical Research and Manufacturers of America noted in 2004 that clinical registries must be careful to protect proprietary information from competitors.

Under the Food, Drug, and Cosmetic Act (FDCA), “any method or process which as a trade secret is entitled to protection.” During an NIH Public Meeting on expansion of ClinicalTrials.gov, a representative of the Advanced Medical Technology Association stated that requiring posting full trial protocols would be in violation of the FDCA since such documents “frequently contain information about the actual device including information about materials, design, and construction of the device.”

Conclusion

Evidence and professional opinion suggest that greater transparency of methodological data would aid researchers in interpreting results and verifying the conclusions of clinical trials. Research on the direct effects on patients of disclosing such information is lacking. However, it is possible for transparency to be improved while continuing to protect proprietary information, as demonstrated by recent policies of some peer-reviewed journals.

Making proprietary information publicly available could potentially drive down competition and make companies less likely to invest in research & development of new drugs. Therefore, the entire protocol should not be required to be provided for public access. Rather, the FDA should clearly define the protocol information that is required for clear interpretation of results and enforce such requirements to the best of its ability.

For more information on this issue, contact the Kulkarni Law Firm.