Why industry should register and disclose results of clinical studies—perspective of a recovering academic
1 Johnson & Johnson Pharmaceutical Research and Development, LLC, 1125 Trenton-Harbourton Road, PO Box 200, Titusville, NJ 08560, USA
Although it's not typical, in a scholarly publication such as the BMJ, to add a personal perspective to a commentary, I believe that in this situation my background is relevant to the discussion. My doctoral dissertation, written in 1988, dealt with the topic of publication bias, which was well described in the Ottawa statement appearing in this issue.1 Since then, I've contributed to several studies of factors affecting publication, including an early empirical demonstration of publication bias.2
, http://www.100md.com
About six months ago, I moved from a university, where I had spent 15 years, to a position in a large pharmaceutical research and development group. Registration and disclosure of the results of clinical studies have, not surprisingly, been topics of numerous conversations where I work.
At this point, as suggested in the Ottawa statement, there is no longer any doubt that studies, whether sponsored by pharmaceutical companies or otherwise, will be registered and their results will be disclosed. This must be viewed as an overall positive step. The debate has changed focus from whether the research process will become more transparent, to how to carry out registration and disclosure. In the long run, openness of the research process will be good for patients, their families, their caregivers, and ultimately for business.
, 百拇医药
The key area of disagreement between industry positions3 4 and other proposals relates to the scope of registries. Specifically, the issue is whether all early phase, exploratory studies, or those not testing hypotheses, require registration and disclosure.
As noted in the Ottawa statement, the industry position is that results from exploratory studies may be provided if the results are regarded as "medically important," and the results could change the labelling of products. Furthermore, results from failed investigational compounds may also be provided if medically important. Clearly, the definition of "medically important" is both crucial to this discussion and subjective in nature. A key component of the interpretation at Johnson & Johnson Pharmaceutical Research and Development is whether the results indicate harm or lack of efficacy, in which case we will disclose results. We would not rely on results of uncontrolled studies in support of efficacy, but when there is suggestion of harm, we have an obligation at our company to report that information. We believe this approach is consistent with the spirit of the Ottawa statement.
, 百拇医药
What about the question of ethical obligations to research participants Clearly, we owe our research participants a huge debt. Does that debt extend to full public disclosure of small, uncontrolled studies By no means am I arguing against disclosure. However, as scientists, we are all aware of the difficulty in interpreting results of small, uncontrolled studies. Even with larger, well controlled studies, there is potential for individual study results to conflict with each other or with the results of meta-analyses of the same questions.5 6 How then are individual patients, or doctors, to interpret conflicting results, especially when the scientists conducting the research are themselves not unanimous in their conclusions
, 百拇医药
So for now, my conscience and I have reached an accord. It is not in anybody's best interest, least of all that of the patients, their families, and their healthcare providers, for industry to withhold vital information on the efficacy and safety (or lack thereof) of marketed products. Prospective registration and full disclosure of study results are steps whose time has come. Disclosure, however, means that we will all have to help patients and doctors understand the limits of conclusions that can be drawn from various study designs and help them understand what these studies mean, and do not mean. Groups such as the Cochrane Collaboration, conducting systematic reviews of existing studies, will have a vital role to that end.
, http://www.100md.com
Competing interests: JAB is a full time employee of Johnson & Johnson Pharmaceutical Research and Development.
References
Krlea-Jeri K, Chan A-W, Dickersin K, Sim I, Grimshaw J, Gluud C, et al. Principles for international registration of protocol information and results from human trials of health related interventions: Ottawa statement (part 1). BMJ 2005;330: 956-8.
Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinical research. Lancet 1991;337: 867-72.
, http://www.100md.com
International Alliance of Pharmaceutical Associations. Joint position on the disclosure of clinical trial information via clinical trial registries and databases. 2005. www.phrma.org/publications/policy//admin/2005-01-06.1113.PDF (accessed 13 Apr 2005).
Pharmaceutical Research and Manufacturers of America. Principles on conduct of clinical trials and communication of clinical trial results, 2004. www.phrma.org/publications/publications/2004-06-30.1035.pdf (accessed 13 Apr 2005).
Cappelleri JC, Ioannidis JP, Schmid CH, de Ferranti SD, Aubert M, Chalmers TC et al. Large trials vs meta-analysis of smaller trials: how do their results compare JAMA 1996;276(16): 1332-8.
Ioannidis JP, Cappelleri JC, Lau J. Issues in comparisons between meta-analyses and large trials. JAMA 1998;279(14): 1089-93., 百拇医药(Jesse A Berlin, senior di)
Although it's not typical, in a scholarly publication such as the BMJ, to add a personal perspective to a commentary, I believe that in this situation my background is relevant to the discussion. My doctoral dissertation, written in 1988, dealt with the topic of publication bias, which was well described in the Ottawa statement appearing in this issue.1 Since then, I've contributed to several studies of factors affecting publication, including an early empirical demonstration of publication bias.2
, http://www.100md.com
About six months ago, I moved from a university, where I had spent 15 years, to a position in a large pharmaceutical research and development group. Registration and disclosure of the results of clinical studies have, not surprisingly, been topics of numerous conversations where I work.
At this point, as suggested in the Ottawa statement, there is no longer any doubt that studies, whether sponsored by pharmaceutical companies or otherwise, will be registered and their results will be disclosed. This must be viewed as an overall positive step. The debate has changed focus from whether the research process will become more transparent, to how to carry out registration and disclosure. In the long run, openness of the research process will be good for patients, their families, their caregivers, and ultimately for business.
, 百拇医药
The key area of disagreement between industry positions3 4 and other proposals relates to the scope of registries. Specifically, the issue is whether all early phase, exploratory studies, or those not testing hypotheses, require registration and disclosure.
As noted in the Ottawa statement, the industry position is that results from exploratory studies may be provided if the results are regarded as "medically important," and the results could change the labelling of products. Furthermore, results from failed investigational compounds may also be provided if medically important. Clearly, the definition of "medically important" is both crucial to this discussion and subjective in nature. A key component of the interpretation at Johnson & Johnson Pharmaceutical Research and Development is whether the results indicate harm or lack of efficacy, in which case we will disclose results. We would not rely on results of uncontrolled studies in support of efficacy, but when there is suggestion of harm, we have an obligation at our company to report that information. We believe this approach is consistent with the spirit of the Ottawa statement.
, 百拇医药
What about the question of ethical obligations to research participants Clearly, we owe our research participants a huge debt. Does that debt extend to full public disclosure of small, uncontrolled studies By no means am I arguing against disclosure. However, as scientists, we are all aware of the difficulty in interpreting results of small, uncontrolled studies. Even with larger, well controlled studies, there is potential for individual study results to conflict with each other or with the results of meta-analyses of the same questions.5 6 How then are individual patients, or doctors, to interpret conflicting results, especially when the scientists conducting the research are themselves not unanimous in their conclusions
, 百拇医药
So for now, my conscience and I have reached an accord. It is not in anybody's best interest, least of all that of the patients, their families, and their healthcare providers, for industry to withhold vital information on the efficacy and safety (or lack thereof) of marketed products. Prospective registration and full disclosure of study results are steps whose time has come. Disclosure, however, means that we will all have to help patients and doctors understand the limits of conclusions that can be drawn from various study designs and help them understand what these studies mean, and do not mean. Groups such as the Cochrane Collaboration, conducting systematic reviews of existing studies, will have a vital role to that end.
, http://www.100md.com
Competing interests: JAB is a full time employee of Johnson & Johnson Pharmaceutical Research and Development.
References
Krlea-Jeri K, Chan A-W, Dickersin K, Sim I, Grimshaw J, Gluud C, et al. Principles for international registration of protocol information and results from human trials of health related interventions: Ottawa statement (part 1). BMJ 2005;330: 956-8.
Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinical research. Lancet 1991;337: 867-72.
, http://www.100md.com
International Alliance of Pharmaceutical Associations. Joint position on the disclosure of clinical trial information via clinical trial registries and databases. 2005. www.phrma.org/publications/policy//admin/2005-01-06.1113.PDF (accessed 13 Apr 2005).
Pharmaceutical Research and Manufacturers of America. Principles on conduct of clinical trials and communication of clinical trial results, 2004. www.phrma.org/publications/publications/2004-06-30.1035.pdf (accessed 13 Apr 2005).
Cappelleri JC, Ioannidis JP, Schmid CH, de Ferranti SD, Aubert M, Chalmers TC et al. Large trials vs meta-analysis of smaller trials: how do their results compare JAMA 1996;276(16): 1332-8.
Ioannidis JP, Cappelleri JC, Lau J. Issues in comparisons between meta-analyses and large trials. JAMA 1998;279(14): 1089-93., 百拇医药(Jesse A Berlin, senior di)