Clinical trials can provide lifesaving options for some of the more than 60 million critically ill Americans. Yet, due to recent public scrutiny, clinical trials have come under fire based on isolated incidents that have caused some to question the efficacy and safety of trials. According to the Association of Clinical Research Profes sionals (ACRP), this perception is unfortu nate, since clinical trials are an essential step in bringing new drugs to market. Drug safety is a major concern of pharmaceutical companies. The wellbeing of patients and the companies’ reputations and financial wellbeing depend on the safety of their products. Companies actively sponsor the necessary tests to learn as much as possible about a drug before it is marketed. But, even as drug companies strive to bring new products to market, the industry is having to contend with a relatively new challenge — litigation on clinical trials. Sev eral highprofile deaths in the past few years have attracted the attention of the media, gov ernment agencies, and lawyers, creating another obstacle for individuals and compa nies initiating or conducting clinical trials. The issue was brought to the fore following the 1999 death of 18yearold Jesse Gelsinger,

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Clinical trials are coming under increased scrutiny by the media and legal communities, forcing sponsors, monitors, and investigators to evaluate the way they approach patient safety issues JOHN HOLLWAY It’s important that we have a certain amount of self regulation, but it’s also important that people understand the consequences of not following those regulations. 27 PharmaVOICE J a n u a r y / F e b r u a r y 2 0 02 TRIAL liability the number of products being tested, and some complacency in the clinicaltrial system. “Clinical trials haven’t faced a great deal of litigation in the past,” says Jill Wadlund, life science casualty manager at Chubb Group of Insurance Companies. “But litigation has started to feed off a bad case, starting to some extent with the University of Pennsylvania’s Gelsinger case. Since then, clinical trials have attracted the attention of the media, govern ment, and lawyers.” These highprofile cases have some con cerned as to whether the industry is doing enough to protect patient safety, which has become key in the litigant’s line of attack, says who was a research volunteer in an experiment at the University of Pennsylvania. A year later, his family filed suit against the university con tending there were serious scientific and regu latory lapses in the experiment. Since then, several cases have been filed and received keen media attention. When Ellen Roche, 24, died last June during a study at Johns Hopkins University into how healthy lungs fight asthmalike conditions, the issue of clinicaltrial safety gained further prominence. Insurers warn that the number of lawsuits involving clinical trials is likely to rise, attributing the increase to several factors — heightened media attention, a large increase in ADDRESSINGHUMAN SUBJECT PROTECTIONRIGHTS.The Department of Health andHumanServices and the U.S. Foodand DrugAdministration have askedThe Institute of Medicine to conduct a twoyear study, with a sixmonth fast track component, to address: accreditation standards for Human Research Participant Protection Programs (HRPPPs);the overall structure and functioning of human subject protection activities, including but not restricted to IRBs; and criteria for evaluating the performance of HRPPPs. Alberto Grignolo, Ph.D. , senior VP and general manager of worldwide regulatory affairs, Parexel International,serves asexpert adviser to the CommitteeonAssessing the System for Protecting Human Research Participants, which is conducting the study,and says the work will be completed by September 2002. “Within the scope of the deliberations, we are looking at the role of each of the partici pants in the clinicalresearch enterprise — IRBs, investigators, sponsors, CROs, and the par ticipants themselves — with a view toward identifying elements of what might constitute a national system for the protection of humanresearch participants,”he explains. PHYSICIANPATIENT RELATIONSHIPS — MAINTAINING OBJECTIVITY. “A recent report from the Inspector General (The Globalization of Clinical Trials: A Growing Challenge in Protecting HumanSubjects) raises some important issues,”says Edgar Adams,Sc.D.,senior VP for clinical research at Harris Interactive.“One of the aspects of the report addresses doc tors who target their own patients. In a physician/patient relationship the physician’s responsibility is toward the patient; in an investigator/subject relationship the responsibili ty is to the study. By targeting their own patients, doctors are walking a tightrope and it is incumbent upon them to be extra aware of issues such as informed consent.” DEVELOPING GOOD SCIENTIFIC METHODS. While tighter regulations might go some way to minimizing concerns,Lawrence A.Meinert, M.D.,senior VP of global and clini cal operations,Covance Inc., contents that FDA regulations tend merely to create a layer of bureaucracy within the pharmaceutical industry. What is needed, he says, is a scientific method to improving safety, or what he refers to as an integrated holistic approach to patient protection. “Most pharmaceutical companies have a safety department, but that department is focused on the rapid processing of serious adverse events,”he explains.“But in biology more subtle problems emerge before something as dramatic as a hospitalization or a death occurs. By following a scientific approach, problems can be detected early enough and unnecessary harm can be prevented.” Developing Industry Standards Lawrence A. Meinert, M.D., senior VP of global and clinical operations at Covance Inc., a drug development services company. “Liti gants contend that while the industry doesn’t hide safety, it doesn’t investigate safety issues as thoroughly as it should. And there is a lot of evidence that would support that line of attack,” he says. So far, says David B. Clissold, an attorney with Hyman, Phelps & McNamara, P.C., very little clinicaltrial litigation has actually gone to court. “There is not a lot of legal analysis of what it’s like to raise a claim that is based on the Nuremberg Code and the Declaration of Helsinki, which, includes participants’ `right to be treated with dignity,”’ he says. “It’s not clear how these types of claims will play out in the legal arena.” The publicity that the Jesse Gelsinger case and others like it have attracted is not unrea WEHAVE AN IRB SYSTEM THAT IS OFTEN OVERWORKED AND LACKING IN NECESSARY EXPERTISE. THEY DON’T ALWAYS SELECT THE BEST INVESTIGATORS,BUT RATHERTHEY SELECT PEOPLEWHO ARE SEEN ASTHOUGHT LEADERS RATHERTHAN THOSE WHOHAVE THE NECESSARY TRAINING IN CONDUCTING CLINICAL TRIALS PER GCPS. Jill Wadlund 28 J a n u a r y / F e b r u a r y 20 0 2 PharmaVOICE TRIAL liability sonable, according to John Hollway, senior VP of marketing and privacy officer of Acurian Inc., a provider of clinicaltrial patient and investigator recruitment solutions for the global biopharmaceutical industry. “This is a very sensitive, important arena,” Mr. Hollway says. “It’s important that we have a certain amount of self regulation, but it’s also important that people understand the conse quences of not following those regulations.” Part of the problem, Ms. Wadlund main tains, is it appears some complacency occurred within the clinicaltrial system oversight pro cess. “We have an IRB system that is often overworked and lacking in necessary exper tise,” she explains, referring to the Institution al Review Boards, which are responsible for Grignolo, Ph.D., senior VP and general man ager of worldwide regulatory affairs at Parexel International, a contract research organization. “Some of the issues surrounding clinical research and drug trials in recent times have to do with poor compliance with established Good Clinical Practices, regulations, and guidelines, including not only those from the FDA but also from the International Confer ence of Harmonization, which has promulgat ed its own guidelines on GCP, dating back to 1997,” Dr. Grignolo says. The regulations and guidelines are in place to address the allimportant issues of informed consent, investigator and sponsor/monitor responsibilities, clinical drug supplies accountability, institutional review board roles and responsibilities, how to handle clinical data and, ensure their scientific validity, and how to safeguard the protection of human research participants. Monitors (also known as clinical research associates or CRAs) are employed by sponsors or CROs to review the conduct of clinical studies regularly to assure that clinical investigators and other site staff abide by their obligations for the product con duct of clinical trials. But Dr. Meinert believes the industry needs to go beyond conforming to regulations, and instead should take a more scientific approach with regard to safety. Alberto Grignolo, Ph.D. overseeing the safety of humans in clinical research. “We have seen sponsors not selecting clinical investigators for the right reasons. For example, they don’t always select the best investigators, but rather they select people who are seen as thought leaders rather than those who have the necessary training and experience in conducting clinical trials per good clinical practices. Also there is a tendency to try to dis avow/abdicate responsibility or accountability to the other parties involved in the process. “What we tell our clients is that ultimate ly any deficiencies are going to be seen as their fault because they are the ones benefiting most from the study and therefore have ultimate responsibility of the process. That’s how a jury will view it,” Ms. Wadlund says. Dr. Meinert agrees that there are huge defi ciencies in the clinicaltrial system, though he maintains the problem is not so much with complacency as it is with denial. “Everyone believes that safety is the most important issue, but there is an unwillingness to concede that safety procedures aren’t being handled in an optimum way,” he says. Another problem for sponsors and contract research organizations is that lawyers need only question the ethics of a study, not neces sarily whether it resulted in injuries. “In clinical trials there is an emerging issue of action called dignity harm, which has been used in civilrights litigation,” Ms. Wadlund says. “With this approach physical injury does not have to be proven, just that the subject involved in the trials was harmed somehow. Therefore, what lawyers often will point to is the ethics of conduct of the study.” Any wellrun clinical trial is carefully reviewed for medical ethics, patient safety, and scientific merit by the research institution. Every study should provide for monitoring the data and the safety of patients on an ongoing basis. How a clinical trial is conducted, there fore, will be a central issue in a courtroom. “In clinical trials there is a thing called the `scientific method,’ which involves hypotheses, and trials are conducted by gathering evidence for and against hypotheses,” Dr. Meinert explains. “In clinical trials, typically that scien tific method is applied toward the benefit side of the equation — otherwise known as efficacy. But there is a very limited use of the scientific method with regard to the safety issue. “The industry is extraordinarily vulnerable in that context, so whenever a drug happens to cause harm in the marketplace, the industry can come under attack for not conducting tri als with reasonable care,” Dr. Meinert says. “All litigants have to do is attack the systems and processes in the industry today.” Solutions to the Problem Compliance with Good Clinical Practice is the key to minimizing risk, contends Alberto EVERYONE BELIEVES THAT SAFETY IS THE MOST IMPORTANT ISSUE, BUT THERE IS AN UNWILLINGNESSTO CONCEDETHAT SAFETY PROCEDURES AREN’T BEING HANDLED IN AN OPTIMUMWAY. Lawrence A. Meinert, M.D. SOME OF THE ISSUES SURROUNDING CLINICAL RESEARCH ANDDRUG TRIALS HAVE TO DOWITH POOR COMPLIANCE WITH ESTABLISHED GOOD CLINICAL PRACTICES, REGULATIONS,AND GUIDELINES, INCLUDING NOT ONLY THOSE FROM THE FDA BUT ALSO FROM THE ICH,WHICH HAS PROMULGATEDTHE GUIDELINES ONGCP. 29 PharmaVOICE J a n u a r y / F e b r u a r y 2 0 02 TRIAL liability “The industry has the illusion that if it con forms with FDA regulations or regulations in Europe that it is protected from litigation and that is absolutely and equivocally not true,” Dr. Meinert contends. “Conforming with the regulations as a minimum does not mean that a company is taking every reasonable measure to protect the patient.” Researchbased pharmaceutical companies and the FDA, according to Pharmaceutical Research and Manufacturers of America (PhRMA) take extraordinary measures to Recruitment is a vital first step in the consent process,one that mustnot in any waybe coer cive or misleading to the potential subjects. SPONSORS AND INVESTIGATORS USE FOUR MAIN STRATEGIES TO RECRUIT HUMANSUBJECTSAND ENCOURAGETIMELY RECRUITMENT: n Sponsors offer financial and other incentives to investigators to boost enrollment n Investigators target their own patients as potential subjects n Investigators seek additional subjects fromother sources such as physician referrals and disease registries n Sponsors and investigators advertise and promote their studies CONCERNS REGARDING SUCHSTRATEGIES: n Erosion of Informed Consent: The consent process may be undermined when under pressure to recruit quickly, investigators misrepresent the truenature of the research or when patients are influenced to participate in research due to their trust in their doctor. n Compromise of Confidentiality: Concerns about someone other than the patient’s physician searching medical records and then contacting a patient about participation. Concerns also are raised about investigators’ use of other records such as disease registries, school records, or mailing lists. n Enrollment of Ineligible Subjects: Research observers fear some investigators may be led to enroll subjects that are ineligible,or of questionableeligibility,to meetquotasand sat isfy sponsors. n Oversight of the recruitment of human subjects is minimal and largely unresponsive to emerging concerns. n IRBs are not reviewing manyof the recruitment practices that they and others find most troubling. n IRBs’ limited review of recruitment practices is in part due to their perceived lack of authority to review certain practices. n HHS provides little guidance to IRBs on acceptable recruitment practices, nor does HHS pay much attention to recruitment practices in its inspections of IRBs and investigators. n In their own oversight of research sites, sponsors pay minimal attention to how human subjects are recruited. RECOMMENDATIONS: n Provide IRBs with direction regarding oversight of recruitment practices. n Facilitate the developmentof guidelines for all parties on appropriate recruiting practices. n Ensure that IRBs and investigators are adequately educated about human subject pro tections. n Strengthen federal oversight of IRBs. Source:The Office of the Inspector General,Department of Health and Human Services’report,“Recruit ing Human Subjects: Pressures in IndustrySponsored Clinical Research.” Patient Recruitment ensure the safety and efficacy of all approved prescription medicines in the U.S. Currently, the drug development and approval process takes an average of 14.2 years due, in large part, to the careful and methodical measures taken by pharmaceutical companies and the FDA to ensure that drug benefits outweigh any risks. Pharmaceutical researchers are conducting more clinical trials with more patients than ever before. This means that more information about the benefits and risks of new chemical entities is being developed than in the past. Pharmaceutical companies and the FDA know, however, that no medicine is ever risk free. Unfortunately, in spite of all of the deter mined efforts of pharmaceutical companies and the FDA to ensure the safety of each new product, there always will be the possibility of risk for patients. Despite due diligence on the part of the industry, according to Dr. Meinert, pharma ceutical companies aren’t going far enough in hypothesizing potential risks. “The industry is focused on an approach called expectedness, which refers to problems that have been clearly identified,” he explains. “But early in the investigation process, that knowledge is limited. What companies need to do to make themselves less vulnerable to lit igation is to offer good scientific inference or speculation.” On the Defensive While undoubtedly a thorny issue, clini caltrial litigation is not an insurmountable problem, Ms Wadlund says. “We’re trying to get companies to recognize that there are some things they can do to make any legal cases against them more difficult to portray,” she says. “We want companies to do a much more effective job of screening and mon ito ing clinical investigators, and also do some due diligence on the qualifications of the IRB.” John M. Isidor, JD, who is a lawyer and CEO of Schulman Associates Institutional Review Board Inc., an independent IRB, con curs that monitoring investigators is essential. “The monitoring and the selection of investigators is critical,” Mr. Isidor says. “Sponsors and CROs need to select investiga tors and coordinators and investigative sites that have an invested interest in the research. Investigators need procedures to ensure that if there are protocol deviations or serious adverse events, they are reported appropriately and timely to the sponsor, CRO, and the IRB. Companies need to insist that investigators are actively involved in research.” A central aspect of the process is matching the right investigator to a particular study. In an effort to meet those criteria, Acurian draws on its database of more than 40,000 experi enced clinicaltrial investigators. “We’ve aggregated a range of data that 30 J a n u a r y / F e b r u a r y 20 0 2 PharmaVOICE TRIAL liability help us identify investigators who are likely to have the most success, primarily in recruiting but also, hopefully, in conducting an actual study,” Mr. Hollway says. “On the patient side, we’ve built a database of more than 1.3 million individuals or households who have said they want to be contacted by Acurian with information about advances in medicine and/or participation in clinical trials. Because this yields a more targeted pool of potential participants, we believe it can lead to better risk management.” Monitoring the Situation To ensure greater objectivity, pharmaceuti cal and biotech companies need to give more authority to monitors, whether that be their own monitors or CROs, and then respond to the monitors’ concerns, Ms. Wadlund says. “The monitor might see a problem, but because the investigator is a thought leader that the company wants to use, there might be a tendency to ignore what the monitor says,” Ms. Wadlund warns. In the case of CROs, how a drug company reacts to the monitors’ advice can be prob lematic. “Sometimes a CRO knows there is a prob lem, and reports it to the customer who is hes itant to do anything about it,” Ms. Wadlund says. “That causes a dilemma. When a CRO acts on behalf of a sponsor it has the same exposure as the sponsoring company. Most clinicaltrial litigation isn’t about the product, it’s about how the study was done, it’s about an improper informed consent process, it’s about whether a person should even have been in a study.” According to Ms. Wadlund, ensuring patient safety in a clinical trial comes down to how much effort and importance the company places on the monitoring process, screening the clinical investigators, and some level of screening of the IRBs to make sure they are competent. If the company doesn’t provide some oversight of those groups, it exposes itself to litigation. The attention that pharmaceutical compa nies pay to safety plays a large part in whether Covance will bid for a project, Dr. Meinert says. “We look at whether the risks with regard to safety outweigh the real benefits, and also whether the client is willing to pay for the extra safety procedures that we apply, before we accept a job.” Once the investigation begins, it is crucial that monitors ensure that clinical protocol is adhered to, Dr. Grignolo says. “The reason the protocol is so important is that it describes exactly what must be done in the trial and should therefore be followed to the letter,” Dr. Grignolo says. The protocol defines how patients must be selected by applying the inclusion and exclusion criteria, “I haven’t seen sponsors or CROs doing much differently in response to these lawsuits, but IRBs sure are, particularly as we are seeing IRB members being named individually in some of these suits,” Mr. Clissold says. “IRBs are looking at these types of trials with a much closer eye, they’re bringing in outside review ers, they’re asking investigators to conduct comprehensive literature searches, and they are gathering more information about the study than ever before.” IRBs also are asking companies to provide more information on the investigators they are using. Because IRBs are better prepared and are looking at studies more closely, sponsors are spending more time and money on proto col development and on protocol changes that respond to an IRB’s concerns. In addition, many IRBs have recognized that they need more resources to properly review study proto cols and several have implemented “protocol review fees” to pass some of those costs on to sponsors. Thus, that increased threat of litiga tion will affect the sponsor’s costs of conduct ing the clinical trial. “In terms of investigators, our IRB ques tions their history with their state medical boards, hospital staff appointments, their his tory with the FDA, and with previous IRBs,” Mr. Isidor says. “I don’t think the sponsors and CROs always ask those questions during an initiation visit. They really should.” Mr. Hollway concurs: “We prescreen an investigator before we give the investigator’s name to the sponsor, and one of the pieces of information that we maintain is whether there is an FDA audit in their file.” Patient Recruitment Another problem, Ms. Wadlund says, is the issue of testsubject enrollment. “It is important to determine if there are conflicts of interest,” she says. “Are people being coerced into taking part with temptations of too much money? We are not suggesting companies should avoid enrollment incentives, rather we suggest they offer incentives in concert with compliance of the protocol — ensuring that a study only includes the people who should be in it, and with proper informed consent.” To that end, experts say companies need to put in place stringent practices on patient recruitment. “For CROs and others involved in clinical trials, the focus needs to be on patient recruitment and exclusion/inclusion criteria,” says Paul Cisternelli, VP and general manager of safety solutions at Phase Forward Inc., a company that provides software, including clinicaltrial data management sys tems to the pharmaceutical industry. “It’s a matter making sure that the patients participating in the study meet the stringent requirements,” he says. There are ways to streamline that process, FOR CROS AND OTHERS INVOLVED IN CLINICAL TRIALS,THE FOCUS NEEDS TO BE ON PATIENT RECRUITMENT AND EXCLUSION/ INCLUSION CRITERIA. IT’S A MATTER MAKING SURETHAT THE PATIENTS PARTICIPATING IN THE STUDY MEET THE STRINGENT REQUIREMENTS. Paul Cisternelli what treatments will be administered to the patients and how often, how many patient vis its are required, what tests will be performed during each visit, what safety monitoring pro cedures and endpoints will be utilized, and all other provisions aimed at protecting the health and safety of participants. In addition, the protocol ensures that the data collected during the trial are scientifically valid and will enable the sponsor and the FDA to make a decision regarding the safety and efficacy of the drug. According to industry experts, identifying protocol deviations is an extremely important function of monitoring, and one that trained monitors are able to spot, document, and address in a timely fashion. Mr. Clissold asserts that while the increased threat of ligitation may not have changed the way that companies monitor clinical trials, IRBs have begun to adjust the way they go about their business and that in turn has affected sponsors. 31 PharmaVOICE J a n u a r y / F e b r u a r y 2 0 02 TRIAL liability he says. “Software can enforce good business practices, though it can’t take on the responsi bility of overseeing the process. If the user is asking the right questions, then the software can assist in making the process more system atic. If that in turn helps people avoid mis takes, it expedites the whole process.” Informed Consent Crucial to patient recruitment is ensuring that those involved in a study are adequately informed, says Edgar Adams Sc.D, senior VP for clinical research at Harris Interactive, a market research and consulting company. “We have large Internet panels that we use for clinicaltrials recruitment,” Dr. Adams says. “Before a study is initiated we survey a sample patient population and have them read key elements of the informed consent. We then give them a test to determine whether they understood what they have read. “We did one study, for example, where only 20% of the patients understood the objective of the study,” he says. “That raises the question of whether that is truly informed consent.” “Everyone knows adverse events can hap pen when you’re testing experimental drugs,” Mr. Hollway says. “What’s important is that companies make the risks known to the par ticipants, and that the participants know the risks they’re taking.” Raising the Bar Government agencies play close heed to the problems inherent in the clinicaltrial process. In November, the Office of Human Research Protections, or OHRP, a branch of the Depart The Office of Human Research Protections (OHRP), U.S. Department of Health and Human Services, has awarded a contract to the Health Improvement Institute to create a national awards program recognizing excellence in protection of human research subjects.The pro gram — Award for Excellence in Human Research Protection — was instituted to encour age and to recognize excellence and innovation in human research protection.The awards program represents an innovative publicprivate partnership.The institute expects to estab lish initially the following three annual awards,and to announce the first award recipients in December 2002: n BEST PRACTICE — given to a research institution, team (i.e., Institutional Review Board),or individual n INNOVATION — given to an individual (or research team) that produces the greatest contribution to advancing human research protection n LIFETIME ACHIEVEMENT — given to an individual The institute is establishing an Award Advisory Board,comprised of government, indus try, and consumer representatives, to provide advice on all aspects of the awards program for recognizing best practices, innovations (research reports) that contribute to advances, and lifetime achievement, in human research protection. Any institution or investigator who conducts research involving human beings, includ ing medical and social science research, or who contributes to human research protection, is eligible to compete for the awards. According to Greg Koski, Director OHRP, “These Awards for Excellence in Human Research Protection will encourage institutions, investigators, and sponsors to continually improve their processes.For too long we have focused on regulatory compliance as an end in itself — what we need to emphasize is prevention of harm.These awards will heighten awareness of these issues within the research community and among the general public, adding credibility to the research process and raising public confidence in research results. We believe that the research community, industry, and the American public share these goals and these awards will recognize the best among those who achieve them.” TheHealth Improvement Institute,Bethesda,Md., is anonprofit,tax exempt organization that promotes improving the quality and productivity of America’s healthcare. Rewarding Excellence ment of Health and Human Services, awarded a contract to the Health Improvement Insti tute to create a national awards program recog nizing excellence in protection of human research subjects (see box on this page). The program’s aim is to encourage improvement in the system to protect human research subjects by giving visibility to best practices and by rewarding institutions, inves tigators, sponsors, and review boards for their commitments to responsible conduct of human studies. But some in the industry, while praising the goal of the awards program, envision a downside. IN A PHYSICIAN/ PATIENT RELATIONSHIP THE PHYSICIAN’S RESPONSIBILITY IS TOWARD THE PATIENT; IN AN INVESTIGATOR/ SUBJECT RELATIONSHIP THE RESPONSIBILITY IS TO THE STUDY.BY TARGETINGTHEIR OWN PATIENTS DOCTORS ARE WALKING A TIGHTROPE AND IT IS INCUMBENT UPON THEM TO BE EXTRA AWARE OF ISSUES SUCH AS INFORMED CONSENT. Edgar Adams, Sc.D. 32 J a n u a r y / F e b r u a r y 20 0 2 PharmaVOICE TRIAL liability “With productliability litigation, which includes clinical trials, companies are always judged based on stateoftheart practices or best practices,” Ms. Wadlund says. “Right now companies first are judged by what the FDA requires, and then to group best practices. If there are companies that actively pursue the award program, do a good job, conduct best practices, and their approach becomes public, it is likely that every other company will be judged against that. Some companies may not have the money to put in place the standards set by those pursuing the award program. However, if that means that all companies do a better job, that of course is a positive.” Mr. Clissold agrees. “I’m concerned that if the standards are so expensive or so onerous that only the larger pharma companies can afford to meet them, then some of the smaller companies won’t be able to achieve those standards. On the other hand, the institute overseeing the awards isn’t a federal government agency, so if a company doesn’t meet those standards there shouldn’t be a penalty so long as the company is in compliance with federal regulations.” Mr. Hollway, too, has reservations about how effective the program will be. “I’d like to think that everyone can agree on what best practices are,” Mr. Hollway says. “But there are so many differences between therapeutic areas as to what needs to happen in a particu lar study for clinical significance that I suspect that best practices is a fairly elusive concept.” According to Mr. Clissold, pharmaceutical and biotech companies, as well as CROs, always have been very involved in the over sight of clinical trials, partly because they want to protect themselves against possible litigation, and partly because they want to get their products approved. “The drug companies and CROs have always had an eye toward patient protection and patientsafety issues,” Mr. Clissold says. “The majority of companies have always done these kinds of studies right. If anything, the fear of litigation might increase their awareness of how important it is to do things right.” Dr. Grignolo defends that view. “Everyone has bought into GCP as being the standard and everyone is trying their best to be in com pliance with all the provisions of good clinical practice. As with any situation involving laws and regulations there will be a range of com pliance, depending on organizations, individ uals, and circumstances. But everyone under stands that GCP compliance is the right thing to do for the best interest of study participants and therapeutic medicine itself.” But Ms. Wadlund believes there is more that needs to, and can be done, to limit com panies’ legal exposure. “There is certainly a segment within the lifescience arena that has been reluctant to admit that there has been a change in litiga tion exposure in the clinicaltrial area, and that called `continuousrisk management.’ This methodology is the kind of paradigm that the pharmaceutical industry can apply, because drug development is like rocket science.” F PharmaVoice welcomes comments about this article. Email us at [email protected]. EDGARADAMS,SC.D.SeniorVP for clinical research, Harris Interactive, Rochester,N.Y.; Harris is a market research and consulting company PAULCISTERNELLI.VP and general manager of safety solutions, Phase Forward Inc.,Waltham, Mass.; Phase Forward is a provider of software to the pharmaceutical market DAVID B.CLISSOLD.Attorney,Hyman, Phelps & McNamara,Washington,D.C.; Hyman,Phelps &McNamara is a law firm ALBERTO GRIGNOLO,PH.D.Senior VP and general manager of worldwide regulatory affairs, Parexel International, Waltham,Mass.; Parexel is a contract research organization JOHNHOLLWAY.SeniorVP of market ing and privacy officer, Acurian Inc., Horsham, Pa.; Acurian is a provider of clinicaltrial patient and investigator recruitment solutions for the global biopharmaceutical industry JOHNM. ISIDOR,JD.Attorney and CEO,Schulman Associates Institutional Review Board Inc., Cincinnati;Schul man Associates is an independent IRB LAWRENCEA.MEINERT,M.D.Senior VP of global and clinical operations, Covance Inc., Princeton,N.J.; Covance is a drug development services company JILL WADLUND.Life science casualty manager,Chubb Group of Insurance Companies,Warren,N.J.; Chubb is a national and international insurance company that provides products for financial institutions, executive protection, and hightech,biotech, and emerging technology industries Experts on this topic I HAVEN’T SEEN SPONSORS OR CROS DOING MUCH DIFFERENTLY IN RESPONSETO THESE LAWSUITS,BUT IRBS SURE ARE, PARTICULARLY ASWE ARE SEEING IRB MEMBERS BEING NAMED INDIVIDUALLY IN SOMETHESE SUITS. David Clissold they need to do a lot more in regard to patient safety,” Ms. Wadlund says. Risk Management Experts say gaining a consensus with regard to industry standards is difficult because of eco nomics, available resources, and timing issues. Altering the procedures as to how companies conduct clinical trials would be costly and timeconsuming, however, there are benefits, aside from reducing the risk of litigation. “We have discovered that the companies that practice good riskmanagement tech niques in all aspects of their operations tend to be very successful in business in general,” Ms. Wadlund says. The question for the industry is how it can best achieve the changes needed to ensure greater safety standards. For an example of how to go about those changes, the industry would be well advised to look to NASA, says Dr. Meinert. “For some years, NASA operated under the model of `fasterbettercheaper,’ which is basically the model of the CRO indus try,” Dr. Meinert explains. “But `fasterbetter cheaper’ leads to a profound risk of catastroph ic failure. NASA has developed an approach

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