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What’s on your mind Opinions Registering results: A public database of clinical-trial information Consumer groups, professional medical associations, and medical journals are calling for public disclosure of all medical studies and drug manufacturers to register their clinical trials in a public database once the trials begin. PharmaVOICE asked: should companies have to register their clinical trials as they are initiated in a public database? Great concept I think this is great concept. Not only will patients be able to know what is available to them aside from the regular treatments for common diseases, but more importantly these data will be available to those who don’t have any other recourse but to try drugs that show promise in clinical trials but are not yet on the market. Carlos Chua Senior Clinical Research Associate Organon Pharmaceuticals USA Inc. Collective best interest It is in our collective best interest for the results of well-designed, carefully conducted clinical trials to be widely available during the development of new pharmaceutical products and after approval. It allows those who will use the product to understand more about it, both positive and negative. We often learn more from our failures than we do from our successes. But simply registering a study does not mean that it was well-designed at the outset nor that it will ever be completed, perhaps due to problems unrelated to the scientific merit of the product, i.e., poor enrollment, uncertain methodology, or endpoints of disease that are not universally accepted. Perhaps the assumptions about variability and the difference between treatments used for calculating sample size were not met, resulting in a nonsignificant difference. It is called “research” for a reason. If we knew the answers at the start, we wouldn’t have to conduct the study. The industry is highly regulated, and sponsors are required to report the results of all studies to the FDA and other involved regulatory bodies around the world. The proprietary information submitted by the sponsor is rigorously reviewed by the agency, and appropriate action by the agency can be expected. The FDA, and presumably other regulatory agencies, is populated by very capable scientific personnel who rigorously protect the public. If regulatory action is indicated, we can expect the FDA to take appropriate action with or without the publication of results of failed studies. The impact of calling for wide dissemination of all information about a drug during development or after approval is not limited to the pharmaceutical industry and regulatory bodies. Perhaps prestigious journals should be “required” to publish reports of “failed” or confirmatory studies as well as those that provide positive data. As a scientific community, we should recognize that negative observations require careful consideration so we neither hide a drug-related problem nor saddle a product with an undeserved black eye. Establishing a registry, whether voluntary or mandatory, does not address the key issues of scientific integrity or comprehensive reporting. The FDA is in place to evaluate medical products and is informed of all regulated studies and results. The agency provides much better oversight than does a registry. George D’Addamio, Ph.D. President PharmConsult Inc. A valuable resource Companies conducting clinical trials are paying for the effort and are responsible for the results, therefore they own the information. But given the fact that companies will be held liable for information they possess, it is in their best interest to make public the fact that they have conducted trials and, at least, any adverse events that are linked causally to the trials. By doing this, they can avoid (to the extent possible) liability for any other reactions that might happen in the future. The cost to companies of any reaction (or even death) that occurred from a reaction they “knew” about would be much worse than any value of keeping that information secret. A database documenting the clinical trial itself, along with any adverse reactions, would be both a prudent and valuable resource. Further information, such as participants, timing, and efficacy might more properly be kept as proprietary information by the company paying for and conducting the trials. Stephen Ruger Project Manager 21 CFR Part 11 Validation An idea with merit The idea of a public trials registry has merit for the following reasons: it puts all sponsors on equal footing regarding accountability for study results; it can speed time to knowledge of favorable (or unfavorable) study results; it can increase public awareness of the success (or failures) associated with conducting trials; it can raise patient awareness of the risks and benefits of participating in clinical trials; and it can help avoid duplicate studies.This registry is consistent with faster and fuller information access and sharing for a common goal. Philip Lavin, Ph.D. President Averion Inc. Full disclosure We are in the age of full disclosure and transparency. Everything must be available to all of us whether it is about mutual funds, criminal records, our time in Vietnam, clinical trials, or company finances. Google went public at an appropriate time. I believe all this is good now that we have digital capacity for storing and retrieving lots of information. The downside of this is that we only have 24 hours in a day and all this information becomes “noise” for most of us who have no time to look at all those envelopes we get in the mail from investment firms. At one level, full disclosure becomes no disclosure at all. The intent of any given trial and the results of any given trial are subject to complex interpretations. A lot of results tossed about without interpretation will be looked at by very few. Few of these things are perfectly clear even to experts. Is it good to have the information out there? Yes. Will large numbers of people pay attention? No. Peter T. Kissinger, Ph.D. Chairman and CEO Bioanalytical Systems Inc. Just say no I say no. In solving a problem, one creates a problem. Who will monitor the reporting and ensure timely submissions? What impact would a delay in completing the trial on time due to unforeseen site issues, such as slow accrual, have on a company’s stock? Cathy Mojzisik, RN, MS Blackburn International Inc. Take extreme care There is no question that publication bias exists, resulting in publishing or publicizing only studies that are considered positive for the drug or device in question. This tends to slant any review of the overall safety and effectiveness across the available evidence toward the positive as well. I believe that something such as the registry of all studies as described can be useful. But presenting summaries of the results from studies that have not been published should be done extremely carefully. An important value of the publication step is the peer-review process. By definition there would be no peer review of those studies not published. Studies are not published for many reasons, not all because of the sponsor’s desire to suppress negative results. Some studies are not published because of the inability to recruit enough patients in the expected or reasonable time frame, or because of unforeseen issues regarding the appropriate execution of the protocol, or the company simply runs out of money. For any of these or similar reasons, a company is typically left with too few subjects to make any informed conclusions on safety and efficacy either way. It is just as biased to claim there is no effect when the study is significantly underpowered, as is the bias resulting from the publication of mainly positive studies. There is a very big difference between the statements “no significant effect was found” and “no conclusion can be reached on the efficacy of this drug due to lack of sufficient data.” Unfortunately, the former is sometimes mistaken for the latter. I would hate to solve one problem by creating another that is equally onerous. One immediate database that would be useful is for studies submitted to FDA and not approved for marketing. Currently, as I understand it, these studies are not available to the general public. In this case, there is significant regulatory and peer review. The question is, why are they not as available as those studies that did result in approval? Howard L. Golub, M.D., Ph.D. President CareStat Inc. A number of positives It is a good idea for a company to have a site at which to register clinical trials. Publicizing the trial can be positive for a number of reasons, all of which could benefit the public and the sponsor. The government has been working on the idea of requiring sites for studies involving life-threatening illnesses. But a large variety of situations, not the least of which is recruiting patients, will affect the schedule on which a trial is maintained. The pharmaceutical and biotech industries should be able to close studies when data show that a CE is not effective or could be hazardous to the patient population. At some time, all studies will have a closing report. James M. Mash President International Pharmaceutical Development LLC Critical to research The industry needs to improve the feedback to investigators on the results of the studies companies conduct. As an investigative site, we want to know what the results were for our studies. More importantly, our research volunteers want to know if they were on placebo or active drug. The research volunteers are giving us and the pharmaceutical industry a gift by participating in research studies. This follow-up communication is critical to the success of continued clinical research. Marion Stamp-Cole Senior Director Clinical Research ProMed Healthcare Research Division Little value to consumers The NIH, with the support of the FDA, has moved to require all recombinant DNA (gene-therapy) clinical trials to be registered. Since this area of medicine is the focus of my firm, the question of posting clinical trials to a public Website is moot. With respect to all other types of clinical trials, I support the release of this information to the FDA but not to the general public. Evaluation of clinical data is far from intuitive, so the persons most likely to comprehend the meaning of the data and apply the information to specific issues are business competitors. This both undermines the cooperation of pharmaceutical firms and provides very little value to the consuming public. The credibility of the FDA to maintain as proprietary all industry information it receives must be inviolate. Without a level of certainty on this issue, compliance would evaporate and the agency couldn’t perform. The FDA can, and should, evaluate all otherwise “secret” clinical data. The complete review of the safety and effectiveness of a product should be based on all the data, not just cherry-picked trials. Paula Wilkerson, RAC Director, Regulatory Affairs Applied Genetic Technologies Corp. Voluntary, not mandatory This information should be registered on a voluntary basis. Let good will and openness drive disclosure. Bill Hahn VP, Marketing & Business Development Shaw Science Partners Inc. Across the board With the new HIPAA rules affecting most in the industry, eventually all CROs and pharma research companies will be subjected to this. Aleecia A. Quinn Clinical Trials Specialist Henry Jackson Foundation Appeasing the critics Yes, all clinical-research trials should be registered in a database the general public can access. This will be the only way to eliminate the negative press clinical research has received. Betsy Payne Watson Independent Clinical Consultant BPW Consulting LLC In support, after trials Since patient care is the most important aspect of drug development, I think clinical-trial data should be accessible to the public. Therefore, I would support the proposal to require drug manufacturers to register their clinical-trials data in a public database. But I’m not sure if registering clinical-trial data during the development phase is appropriate; I would support this proposal after drugs are approved and on the market. Michael Simmons Clinical Data Manager Human Genome Sciences Inc.