MessageFrom: Alan Goldhammer [AGoldhammer@phrma.org] Sent: Monday, August 04, 2003 3:54 PM To: fdadockets@oc.fda.gov Subject: Docket Number 03N-0202 Response to FDA Assessment of Public Perceptions and Knowledge of Clinical Trials and Informed Consent Human Subject Protection (68 Federal Register 22717, June 5, 2003) The following comments on the above noted information request are submitted on behalf of the Pharmaceutical Research and Manufacturers of America (PhRMA). PhRMA represents the country's leading research-based pharmaceutical and biotechnology companies. Our member companies are devoted to inventing medicines that allow patients to lead longer, happier, healthier, and more productive lives. In 2002, our members invested over $32 billion in the discovery and development of new medicines. In general PhRMA supports the idea of the FDA interviewing the public at random to determine their level of knowledge regarding the clinical research process, in order to develop new tools for educating the public about various aspects of the process. There are a number of suggestions that would improve the survey and provide more useful information both to the FDA as well as the others involved in clinical research, including institutions, IRBs, clinical investigators and sponsors. These suggestions are outlined below, and it is anticipated that these would be useful for the FDA to consider in the development of the survey. The survey needs greater clarity than provided in the Federal Register regarding its scope. For example, the question of whether this survey addresses specific drug trial issues or general issues in clinical research (i.e. to include all types of research, including investigator initiated research, NIH and VA sponsored studies, studies using marketed drug, medical device research) needs to be made more transparent. Without a clearer scope, the data collected may be uninterpretable. The survey assumes prior knowledge of terminology (e.g. clinical trial, clinical investigator). Considering the mall-intercept design of the survey, any assumptions about prior knowledge of how drugs get tested prior to marketing or how clinical research is conducted in general, need to be tested first before getting specific about how clinical trials are run and what informed consent is intended to convey. The geographical spread of the survey may miss important communities, for instance in the South. While it is expected that the data would be combined for analysis, by careful selection of sites and comparison of responses across sites, the FDA may be better able to detect where education efforts are most needed. A three-site sample may not be sufficient and may produce results not representative of our country. A clear description of the analyses to be performed should be provided, including information on whether the questions asked have been validated, whether they will accurately assess public knowledge of drug development, and if the data will be available for public review. The time needed for the survey to be read and completed is identified as 15 minutes. The survey has 46 questions. We question that assessment of time considering the likelihood that some questions will need to be repeated. If it does take longer, as PhRMA anticipates, it could result in an inaccurate survey as respondents answer questions quickly without giving their full attention to the questions or their answers, just to complete the survey. The survey does not probe sufficiently for reasons why consumers may not be willing to participate in clinical trials. This would be helpful to coordinate with other current initiatives such as the NIH-NCI/industry collaboration, which is issuing grants to 6 academic medical centers to learn why recruitment into cancer trials has not exceeded 3% of the patient population. Another aspect to explore may be if consumers know how to access information on clinical trials (e.g. public awareness of Clinical Trials Data Bank). The FR states the survey’s outcome is to help in the development of plans to educate the public about clinical research, human subject protection, and informed consent. The FDA should obtain and assess available materials to determine if they would aid in this exercise. One such document published in April 2002 by ECRI is entitled “Should I Enter A Clinical trial?” and may be downloaded free of charge at www.ecri.org. It is a 133-page guide that discusses the issues identified as the educational goals by the FDA. To address the survey proper, please consider the following suggestions. Question #4 asks if the respondent has ever had a serious or life threatening condition for which they required care for a year or more. This implies that clinical trials are only directed toward serious/life-threatening conditions, which is not accurate. It also implies that all such conditions can be treated with pharmaceuticals, which also may not be accurate (e.g., broken hips, joint replacements etc. may require extended recovery and yet not require significant pharmaceutical care). A number of the questions appear repetitive (e.g. #7 & 35; 10, 11 & 12; 17 & 18; 19 – 22; 30 – 33; 39 & 40) and should be redesigned/condensed to shorten the survey. There are six questions regarding payment to investigators that should be condensed (#27, 30-34). The format for question #34 appears too complicated for an oral interview. Questions #35-38 are only to be answered if the subject has participated in a clinical trial. We expect the overwhelming majority of respondents, considering the venue, will be reasonably healthy individuals. These questions should be deleted or perhaps asked in a survey conducted in a different venue, such as the NIH campus or other research-intensive facility where a high proportion of respondents will be and/or have been patients in trials. Question 38 is particularly leading in the context of this survey; it is suggested a control question be asked to assess how much patients were told about their condition or possible side effects during routine treatment for a medical condition. It would be expected that patients outside the research environment are less adequately informed of risks, alternative treatments, etc. than they are within that context. It creates a situation where the subject would have to be informed of every possible side effect in order to answer “no”. In this way the data could be skewed toward making it look like there is a problem with informed consent when in fact there is not a problem. Question 39 deals with theoretical questions as opposed to their experience. This is likely to be misleading. There are several other areas in the clinical research process about which public knowledge should be further explored, and may provide better balance to the survey. For instance, does the public understand that: § before a drug is tested in humans, it is tested in animals at much higher doses for possible safety effects § research is carried on in phases usually starting with low numbers of normal subjects, at a very low doses, to examine for safety issues, before proceeding to greater numbers of patients, with the illness being studied § research will allow new therapies and cures to be developed for current untreatable or under-treated medical conditions § an institutional review board (IRB) must review and approve the study before it starts, and that they have the authority to require modification to the study, may disapprove it, or can stop an ongoing trial if they find it too risky to research participants § before a drug is approved for marketing by the FDA, it has usually been tested in multiple thousands of patients. § new indications for a marketed drug may need to undergo the same extensive testing in humans as the drug did prior to its initial approval § the clinical testing required by the FDA of sponsors for new drugs, differs significantly from the clinical testing in humans required to gain approval for a generic drug As stated by FDA in the Federal Register, the purpose of the survey is to explore the "U.S. consumers' knowledge and attitudes about clinical research and informed consent in clinical research". However it is uncertain if the survey in its present form will provide that critical information. It is noteworthy that FDA has embarked on this project to understand the reasons why consumers are reluctant to participate in clinical trials. Given the critical role of clinical trials in the development of new therapies and the ever-present shortage of clinical trial volunteers, an improved survey could bring a better understanding of the factors hindering volunteer participation in clinical trials and insights into how to address the problem. Alan Goldhammer, PhD Associate Vice President, Regulatory Affairs PhRMA 1100 Fifteenth Street, NW Washington, DC 20005 Phone: 202-835-3533 FAX: 202-835-3597 e-mail: agoldham@phrma.org