Constraints on Publication Rights in Industry-Initiated Clinical Trials

Methods

For all 44 industry-initiated randomized trials that were approved in 1994-1995 by the Scientific-Ethical Committees for Copenhagen and Frederiksberg in Denmark and that resulted in publication, we compared the full trial protocols with all text in the subsequent publications (median publication year, 1999), including footnotes and acknowledgments.³ To look for changes over time as a response to new guidelines and ethical requirements, we also assessed the first 44 industry-initiated trial protocols approved in 2004 by the same committees; insufficient time had passed to assess subsequent publications.

For the 2004 protocols, committee requirements removed information that identified particular sponsors, so we limited our examination to whether the investigators had full access to all of the study data and the investigators' publication rights. Two observers independently extracted data. Different observers reviewed the protocol and corresponding article; there was no other blinding. Disagreements were resolved by discussion. Examples of constraints were extracted from the 2004 protocols; they are available from the authors on request.

Results

Of the 44 trials from 1994-1995, 43 (98%) had multinational pharmaceutical firms as sponsors, and 33 (75%) were multicenter and multinational. According to the protocols, the sponsor had access to accumulating data during 16 trials, eg, through interim analyses and participation in data and safety monitoring committees. Such access was disclosed in only 1 corresponding trial article. An additional 16 protocols noted that the sponsor had the right to stop the trial at any time, for any reason; this was not noted in any of the trial publications. The sponsor therefore had potential control over a trial in progress in 32 (73%) of these studies.

Constraints on the publication rights were described in 40 (91%) of the protocols from 1994-1995 (Table), and 22 (50%) noted that the sponsor either owned the data, needed to approve the manuscript, or both. None of the constraints were stated in any of the trial publications. None of the protocols or trial publications stated that investigators had access to all of the data generated from the trial or had final responsibility for the decision to submit for publication without requiring approval from the sponsor.

Direct comparisons of the 1994-1995 protocol results with data from the 44 protocols from 2004 are limited in that some 2004 trials may never be published. However, we found similar constraints on publication rights in protocols from both time periods (Table). Of the 44 protocols from 2004, 13 (30%) referred to a separate publication agreement between the sponsor and investigators, compared with none of the protocols from 1994-1995. None of these agreements were submitted to the Scientific-Ethical Committees, and they were therefore not available to us. Reasons for which a sponsor could delay publication included a requirement for new or repeated analyses if there were disagreements with the investigators' analyses, inadequate funding for analyses, or the sponsor seeking patent protection.

Comment

Among the protocols we examined, a sponsor had the potential to prevent publication in half of the trials and had recourse to practical or legal obstacles in most of the others. Surveys of US medical schools^1-2 have shown that they frequently engage in industry-sponsored research that fails to adhere to editorial guidelines⁴ regarding trial design, access to data, and publication rights. Eighty percent of the surveyed medical schools would allow a multicenter trial agreement that granted data ownership to the sponsor.² These results are consistent with our findings.

The International Committee of Medical Journal Editors has declared that “researchers should not enter into agreements that interfere with their access to the data and their ability to analyze it independently, to prepare manuscripts, and to publish them” and that “editors may choose not to consider an article if a sponsor has asserted control over the authors' right to publish.”⁴ To improve transparency, trial protocols and publication agreements should be registered and publicly available.⁵ To avoid premature trial termination for reasons that may represent a financial interest, data monitoring committees should be independent and sponsors should not have access to accumulating data.