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Scientific data from clinical trials: Investigators' responsibilities and rights
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Scientific data from clinical trials: Investigators’ responsibilities and rights Based on recent reports,1-9 there are increasing concerns about the control of the scientific data obtained from clinical trials sponsored by industry. Many of the problems encountered are the result of restrictions contained in the research contracts that participating investigators are asked to sign. A number of solutions have been suggested to ensure the integrity of clinical trials, including the establishment of appropriately constituted trial oversight committees, negotiating noninterference pledges from industry sponsors, and creating proactive support of investigators’ rights by organized medicine.10 As surgical journal editors, we stand opposed to inappropriately restrictive contractual agreements governing company-sponsored clinical trials of devices or drugs, such as those containing clauses that deny the investigators proper control over the scientific aspects of the trial or restrict access to the data and their timely publication. We believe that responsibility for the scientific data from clinical trials and its analysis, interpretation, and publication should rest in the hands of the investigators. In multicenter trials, a duly appointed and properly constituted publications committee can and usually should carry out these responsibilities. Recently, the editors of 13 medical journals also published their opposition to inappropriately restrictive research contracts, insisting that investigators be given and assume adequate responsibility for the conduct of a clinical trial, have sufficient access to the data to perform the necessary analyses, and have control over the decision to publish. The editors further stated that they will “routinely require authors to disclose details of their own and the sponsor’s role in the study” and “. . .will ask the responsible author to sign a statement indicating that he or she accepts full responsibility for the conduct of the trial, had access to the data, and controlled the decision to publish” and “. . .will not review or publish articles based on studies that are conducted under conditions that allow the sponsor to have sole control of the data or to withhold publication.”11 Editors may choose not to publish an article if the sponsor had control over the trial design, data analysis, and/or publication. These requirements for publication J Vasc Surg 2002;35:1303-4. 0741-5214/2002/$35.00 ⫹ 0 24/1/123717 doi:10.1067/mva.2002.123717
ethics were adopted as policy on May 11, 2001, and will be included in the next publication of the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals”—a document to which we are all signatories. The revised section on “Potential Conflicts of Interest Related to Project Support” is quoted here. Increasingly, biomedical studies receive funding from commercial firms, private foundations, and government. The conditions of this funding have the potential to bias and otherwise discredit the research. Scientists have an ethical obligation to submit creditable research results for publication. As the persons directly responsible for their work, researchers therefore should not enter into agreements that interfere with their access to the data or their ability to analyze the data independently, to prepare manuscripts, and to publish them. Authors should describe the role of the study sponsor(s), if any, in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the report for publication. If the supporting source had no such involvement, the authors should so state. Biases potentially introduced when sponsors are directly involved in research are analogous to methodological biases of other sorts; some journals therefore choose to include information about the sponsor’s involvement in the methods section of the published paper. If a study is funded by an agency with a proprietary or financial interest in the outcome, editors may ask authors to sign a statement such as, “I had full access to all of the data in this study and I take complete responsibility for the integrity of the data and the accuracy of the data analysis.” Editors should be encouraged to review copies of the protocol and/or contracts associated with project-specific studies before accepting such studies for publication. Editors may choose not to consider an article if a sponsor has asserted control over the authors’ right to publish. We, the undersigned surgical journal editors, support these revised guidelines and, as appropriate, will request authors of reports on clinical or basic research trials of devices and drugs to disclose details of the relative roles of the investigators and the sponsors in the conduct of the trial, the data collection and analysis, and preparation of the submitted manuscript. We may also ask the responsible author to sign a statement that he or she accepts full responsibility for the conduct of the trial, the validity of the data and its analysis, and the writing of the submitted manuscript. 1303
JOURNAL OF VASCULAR SURGERY June 2002
1304 Investigators’ responsibilities and rights
American Journal of Surgery (Hiram C. Polk, Jr, MD) American Surgeon (Talmadge A. Bowden, Jr, MD) Annals of Surgery (Layton F. Rikkers, MD) Annals of Surgical Oncology (Charles M. Balch, MD) Archives of Surgery (Claude H. Organ, MD) British Journal of Surgery (John A. Murie, MD) Current Surgery (Walter J. Pories, MD) Digestive Surgery (Markus W. Buechler, MD, John P. Neoptolemos, MD) Diseases of the Colon and Rectum (Victor W. Fazio, MD) Journal of the American College of Surgeons (Seymour I. Schwartz, MD) Journal of Gastrointestinal Surgery (John L. Cameron, MD, Keith A. Kelly, MD) Journal of Pediatric Surgery (Jay L. Grosfeld, MD) Journal of Surgical Research (David W. McFadden, MD, Wiley W. Souba, MD) Journal of Trauma (Basil A. Pruitt, Jr, MD) Journal of Vascular Surgery (K. Wayne Johnston, MD, Robert B. Rutherford, MD) Surgical Laparoscopy, Endoscopy and Percutaneous Techniques (Maurice E. Arregui, MD, Carol E. H. Scott-Conner, MD) Surgery (Andrew L. Warshaw, MD, Michael G. Sarr, MD) Surgical Endoscopy (Alfred Cuschieri, MD, Bruce V. MacFadyen, MD) World Journal of Surgery (Ronald K. Tompkins, MD)
REFERENCES 1. Rutherford RB, Johnston KW. Potential problems with industrysupported research. J Vasc Surg 2000;31:1066-76. 2. Weatherall D. Academia and industry: increasingly uneasy bedfellows. Lancet 2000;355:1574. 3. Angell M. Is academic medicine for sale? N Engl J Med 2000;342: 1516-8. 4. Bodenheimer T. Uneasy alliance— clinical investigators and the pharmaceutical industry. N Engl J Med 2000;342:1539-44. 5. Goldstein LB, Brott TG, Kothari RU, Smith WS. Clinical stroke trials: guarding against bias. Stroke 1999;30:1165-6. 6. Hailey D. Scientific harassment by pharmaceutical companies: time to stop. CMAJ 2000;162:212-3. 7. Rennie D. Fair conduct and fair reporting of clinical trials. JAMA 1999;282;1766-8. 8. Kahn JO, Cheng DW, Mayer K, Murray H, Lagakos S. Evaluation of HIV-1 immunogen, an immunologic modifier, administered to patients infected with HIV having 300 to 549⫻106/L CD4 cell counts: a randomized controlled trial. JAMA 2000;284:2193202. 9. Blumenthal D, Campbell EG, Anderson MS, Causino N, Louis KS. Withholding research results in academic life science: evidence from a national survey of faculty. JAMA 1997;277:1224-8. 10. Rutherford RB, Johnston KW. Protecting the rights of investigators in industry supported clinical research. J Vasc Surg 2002;35:103640. 11. Davidoff F, DeAngelis CD, Drazen JM, Nicholls MG, Hoey J, Hojgaard L, et al. Sponsorship, authorship, and accountability. N Engl J Med 2001;345:825.
The editors of the Journal of Vascular Surgery strongly endorse the above position paper and the principles that scientific investigators assume appropriate responsibility for the conduct of industry-sponsored clinical trials, have sufficient access to the data to perform all necessary analyses, and have control of the decisions relating to when and where to publish the results. In January of this year, we modified our policies to reflect this position (“Policy on declaring conditions of funding for research studies,” 2002;35:197). Further, in last month’s issue, we wrote an editorial on “Protecting the rights of investigators in industry-supported clinical research” (2002;35:1036-40) suggesting additional broader measures for dealing with the issues involved. Hopefully, these efforts and a broadening support by both surgical and medical journal editors will help reaffirm that the primary responsibility for the scientific aspects of industry-supported research must reside with the principle investigators. These policies were first approved by the editors of a core group of medical journals (Davidoff F, DeAngelis CD, Drazen JM, Nicholls MG, Hoey J, Hojgaard L, et al. Sponsorship, authorship, and accountability. N Engl J Med 2001;345:825). We are pleased that we have developed a core group of surgical editors who also support these policies. —Robert B. Rutherford, MD, and K. Wayne Johnston, MD
Scientific data from clinical trials: Investigators’ responsibilities and rights Based on recent reports,1-9 there are increasing concerns about the control of the scientific data obtained from clinical trials sponsored by industry. Many of the problems encountered are the result of restrictions contained in the research contracts that participating investigators are asked to sign. A number of solutions have been suggested to ensure the integrity of clinical trials, including the establishment of appropriately constituted trial oversight committees, negotiating noninterference pledges from industry sponsors, and creating proactive support of investigators’ rights by organized medicine.10 As surgical journal editors, we stand opposed to inappropriately restrictive contractual agreements governing company-sponsored clinical trials of devices or drugs, such as those containing clauses that deny the investigators proper control over the scientific aspects of the trial or restrict access to the data and their timely publication. We believe that responsibility for the scientific data from clinical trials and its analysis, interpretation, and publication should rest in the hands of the investigators. In multicenter trials, a duly appointed and properly constituted publications committee can and usually should carry out these responsibilities. Recently, the editors of 13 medical journals also published their opposition to inappropriately restrictive research contracts, insisting that investigators be given and assume adequate responsibility for the conduct of a clinical trial, have sufficient access to the data to perform the necessary analyses, and have control over the decision to publish. The editors further stated that they will “routinely require authors to disclose details of their own and the sponsor’s role in the study” and “. . .will ask the responsible author to sign a statement indicating that he or she accepts full responsibility for the conduct of the trial, had access to the data, and controlled the decision to publish” and “. . .will not review or publish articles based on studies that are conducted under conditions that allow the sponsor to have sole control of the data or to withhold publication.”11 Editors may choose not to publish an article if the sponsor had control over the trial design, data analysis, and/or publication. These requirements for publication J Vasc Surg 2002;35:1303-4. 0741-5214/2002/$35.00 ⫹ 0 24/1/123717 doi:10.1067/mva.2002.123717
ethics were adopted as policy on May 11, 2001, and will be included in the next publication of the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals”—a document to which we are all signatories. The revised section on “Potential Conflicts of Interest Related to Project Support” is quoted here. Increasingly, biomedical studies receive funding from commercial firms, private foundations, and government. The conditions of this funding have the potential to bias and otherwise discredit the research. Scientists have an ethical obligation to submit creditable research results for publication. As the persons directly responsible for their work, researchers therefore should not enter into agreements that interfere with their access to the data or their ability to analyze the data independently, to prepare manuscripts, and to publish them. Authors should describe the role of the study sponsor(s), if any, in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the report for publication. If the supporting source had no such involvement, the authors should so state. Biases potentially introduced when sponsors are directly involved in research are analogous to methodological biases of other sorts; some journals therefore choose to include information about the sponsor’s involvement in the methods section of the published paper. If a study is funded by an agency with a proprietary or financial interest in the outcome, editors may ask authors to sign a statement such as, “I had full access to all of the data in this study and I take complete responsibility for the integrity of the data and the accuracy of the data analysis.” Editors should be encouraged to review copies of the protocol and/or contracts associated with project-specific studies before accepting such studies for publication. Editors may choose not to consider an article if a sponsor has asserted control over the authors’ right to publish. We, the undersigned surgical journal editors, support these revised guidelines and, as appropriate, will request authors of reports on clinical or basic research trials of devices and drugs to disclose details of the relative roles of the investigators and the sponsors in the conduct of the trial, the data collection and analysis, and preparation of the submitted manuscript. We may also ask the responsible author to sign a statement that he or she accepts full responsibility for the conduct of the trial, the validity of the data and its analysis, and the writing of the submitted manuscript. 1303
JOURNAL OF VASCULAR SURGERY June 2002
1304 Investigators’ responsibilities and rights
American Journal of Surgery (Hiram C. Polk, Jr, MD) American Surgeon (Talmadge A. Bowden, Jr, MD) Annals of Surgery (Layton F. Rikkers, MD) Annals of Surgical Oncology (Charles M. Balch, MD) Archives of Surgery (Claude H. Organ, MD) British Journal of Surgery (John A. Murie, MD) Current Surgery (Walter J. Pories, MD) Digestive Surgery (Markus W. Buechler, MD, John P. Neoptolemos, MD) Diseases of the Colon and Rectum (Victor W. Fazio, MD) Journal of the American College of Surgeons (Seymour I. Schwartz, MD) Journal of Gastrointestinal Surgery (John L. Cameron, MD, Keith A. Kelly, MD) Journal of Pediatric Surgery (Jay L. Grosfeld, MD) Journal of Surgical Research (David W. McFadden, MD, Wiley W. Souba, MD) Journal of Trauma (Basil A. Pruitt, Jr, MD) Journal of Vascular Surgery (K. Wayne Johnston, MD, Robert B. Rutherford, MD) Surgical Laparoscopy, Endoscopy and Percutaneous Techniques (Maurice E. Arregui, MD, Carol E. H. Scott-Conner, MD) Surgery (Andrew L. Warshaw, MD, Michael G. Sarr, MD) Surgical Endoscopy (Alfred Cuschieri, MD, Bruce V. MacFadyen, MD) World Journal of Surgery (Ronald K. Tompkins, MD)
REFERENCES 1. Rutherford RB, Johnston KW. Potential problems with industrysupported research. J Vasc Surg 2000;31:1066-76. 2. Weatherall D. Academia and industry: increasingly uneasy bedfellows. Lancet 2000;355:1574. 3. Angell M. Is academic medicine for sale? N Engl J Med 2000;342: 1516-8. 4. Bodenheimer T. Uneasy alliance— clinical investigators and the pharmaceutical industry. N Engl J Med 2000;342:1539-44. 5. Goldstein LB, Brott TG, Kothari RU, Smith WS. Clinical stroke trials: guarding against bias. Stroke 1999;30:1165-6. 6. Hailey D. Scientific harassment by pharmaceutical companies: time to stop. CMAJ 2000;162:212-3. 7. Rennie D. Fair conduct and fair reporting of clinical trials. JAMA 1999;282;1766-8. 8. Kahn JO, Cheng DW, Mayer K, Murray H, Lagakos S. Evaluation of HIV-1 immunogen, an immunologic modifier, administered to patients infected with HIV having 300 to 549⫻106/L CD4 cell counts: a randomized controlled trial. JAMA 2000;284:2193202. 9. Blumenthal D, Campbell EG, Anderson MS, Causino N, Louis KS. Withholding research results in academic life science: evidence from a national survey of faculty. JAMA 1997;277:1224-8. 10. Rutherford RB, Johnston KW. Protecting the rights of investigators in industry supported clinical research. J Vasc Surg 2002;35:103640. 11. Davidoff F, DeAngelis CD, Drazen JM, Nicholls MG, Hoey J, Hojgaard L, et al. Sponsorship, authorship, and accountability. N Engl J Med 2001;345:825.
The editors of the Journal of Vascular Surgery strongly endorse the above position paper and the principles that scientific investigators assume appropriate responsibility for the conduct of industry-sponsored clinical trials, have sufficient access to the data to perform all necessary analyses, and have control of the decisions relating to when and where to publish the results. In January of this year, we modified our policies to reflect this position (“Policy on declaring conditions of funding for research studies,” 2002;35:197). Further, in last month’s issue, we wrote an editorial on “Protecting the rights of investigators in industry-supported clinical research” (2002;35:1036-40) suggesting additional broader measures for dealing with the issues involved. Hopefully, these efforts and a broadening support by both surgical and medical journal editors will help reaffirm that the primary responsibility for the scientific aspects of industry-supported research must reside with the principle investigators. These policies were first approved by the editors of a core group of medical journals (Davidoff F, DeAngelis CD, Drazen JM, Nicholls MG, Hoey J, Hojgaard L, et al. Sponsorship, authorship, and accountability. N Engl J Med 2001;345:825). We are pleased that we have developed a core group of surgical editors who also support these policies. —Robert B. Rutherford, MD, and K. Wayne Johnston, MD