WASHINGTON—As cancer clinical trials have become larger and more complex and potentially sensitive patient genomic analyses more common, issues of protecting the privacy and rights of participants in those trials have become more challenging—issues that were explored at a scientific workshop here hosted by the National Cancer Policy Forum (NCPF) of the Institute of Medicine.
Federal regulations such as the Common Rule and the Health Insurance Portability and Accountability Act (HIPAA), which was recently modified, protect the privacy of individually identifiable health information. So do the rules of local institutional review boards (IRBs). But, in an era of massive computerized data collection and increased data sharing to advance scientific knowledge, thorny questions about privacy, rights, and informed consent have arisen. IOM workshop speakers examined many of those issues in detail, and the Institute expects to publish a written summary of their deliberations in about six months.
The current landscape for clinical trial investigators presents “a conundrum,” said NCPF member Richard L. Schilsky, MD, Chief Medical Officer of the American Society of Clinical Oncology and former Chairman of Cancer and Leukemia Group B. Patients' clear right to privacy must be balanced against the vision of a continuous learning system in health care, embraced by both ASCO and the IOM, he noted, pointing out that “you can't do much learning” if new information observed in clinical trials cannot be disclosed.
“IRBs are extremely conservative, by and large. IRBs should become advocates for responsible research—not obstacles.” He added, “I'm of the opinion that we spend a lot of time protecting people from things they don't want to be protected from.”
Another speaker, NCPF Vice Chair Patricia A. Ganz, MD, agreed on the need to balance patient protections with the need for a continuous learning environment in cancer clinical trials and cancer care: “Truly we do need a reset to improve the whole clinical research enterprise; I think we would want every patient potentially to be a research subject,” said Ganz, Distinguished University Professor at the Fielding School of Public Health and Director of Cancer Prevention & Control at UCLA's Jonsson Comprehensive Cancer Center.
Ganz, who moderated a workshop session, chaired the IOM committee that last year published the sweeping 384-page “Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis” report (OT 10/10/13 issue).
Today, protections for cancer patients are becoming more complicated in part because the line between clinical research and care is often blurred, said Angela Bradbury, MD, Co-chair of the IOM workshop planning committee and Assistant Professor in the Division of Hematology-Oncology at the University of Pennsylvania. “Research and clinical care are often intertwined in oncology,” blurring heightened by electronic medical records, she said.
Several speakers described the general willingness of clinical trial participants who signed an initial consent form, especially those who are older, to have their data and/or biospecimens used in future research trials to find cures for cancer. “By the time you're 90, you've gotten the diseases you're going to get,” said Gail Jarvik, MD, PhD, holder of the Arno G. Motulsky Endowed Chair in Medicine and Head of the Division of Medical Genetics at the University of Washington School of Medicine. “The older people just want the problem fixed.”
All the speakers agreed on the need for strong patient privacy protections regardless of subjects' desire to participate in trials, especially in an era of high-profile massive security data breeches. “The sickest people tend to be the most vulnerable… there has to be something in place to protect the most vulnerable,” said Alice Leiter, Policy Counsel for the Center for Democracy & Technology's Health Privacy Project.
While data security breeches have not plagued clinical trial research, in today's era of electronic communication and storage, no database is entirely secure, warned Bradley Malin, PhD, Vice Chair for Research and Associate Professor of Biomedical Informatics at Vanderbilt University School of Medicine. “Given enough effort, you can break into any system… I don't care what people tell you.”
He noted that HIPAA regulations specifically require that collected health information cannot be used to identify an individual, and discussed BioVu, a privacy-protection research repository developed at Vanderbilt of DNA extracted from discarded blood collected during routine clinical testing and linked to de-identified electronic medical records. The goal is to provide a resource to Vanderbilt investigators for studies of genotype-phenotype associations.
In developing BioVu, there were a lot of challenges, he said, pointing out that de-identification of patient information is especially difficult when it is taken from physicians' notes. But, he noted, in “scrubbing” trial participant data, such facts as race and age can be obscured, and geographical areas can be “coarsened.” For example, such terms as “North America” and “Eastern Europe” can be used instead of specific place names.
The clinical trials consent form remains a mainstay of patient protection. Mary McCabe, RN, MA, Director of the Cancer Survivorship Program at Memorial Sloan Kettering Cancer Center and a previous NCI staff member, described how in 1997, the NCI launched an initiative to improve the consent form for clinical trials. Patient advocacy groups wanted change, and even IRB groups were questioning the length and complexity of the documents.
Although the NCI initiative did produce an updated informed-consent template in February 2013 for use in clinical research trials, there is still room for improvement, speakers said. While the new template is more patient-centered, “the document remains too long and overwhelming, and the reading level is still too high,” said Laura Cleveland, Co-Chair of the Patient Advocate Committee of CALGB/Alliance.
While agreeing that a consent form is just one component of patient protection, speakers discussed in detail how to improve the consent form as part of the overall process of enrolling a clinical trial subject. Virtually all speakers agreed with Cleveland that consent forms are still too long, too complicated, too full of medical jargon, and written on too high a reading level—points that she showed vividly in her presentation (http://bit.ly/1hwJ3Gz).
Federal statutes mandate that IRBs ensure that informed-consent standards be written in language lay people can understand, noted Michael Paasche-Orlow, MD, MA, MPH, Associate Professor of Medicine at Boston University School of Medicine. But, he said, the average reading level in the United States is grade eight or nine– “and there is a huge relationship between educational attainment and literacy. So if you don't check, you don't know what the person understands when reading a consent form.”
Paasche-Orlow, who is studying interactive computerized models to improve comprehension of consent forms, recommended that clinical trial investigators “require confirmation of comprehension as an entry criterion” into a study. They can ask potential trial participants, for example, questions such as: “Tell me the goal of this research and what will happen to you if you participate.”
‘Opportunity for Professional Development’
There is a lack now of trained professional adult educators who could explain consent forms to potential clinical trial participants. “This is an opportunity for professional development,” he said. “We need a model training program for informed consent,” which, he predicted, “could shift the culture of research recruitment for the better.”
“There's not an easy fix here,” said Jeffrey Botkin, MD, MPH, Professor of Pediatrics at the University of Utah, where he is also Adjunct Professor of Human Genetics, Chief of the Division of Medical Ethics and Humanities, and Associate Vice President for Research Integrity.
Botkin, Chair of the U.S. Department of Health and Human Services (DHHS) Secretary's Advisory Committee on Human Research Protections (SACHRP), said he believes new regulations or guidance from DHHS are necessary to improve informed consent and make participant forms less daunting and more understandable: “We're trying to give IRBs a little more flexibility in consent forms. My hope is to encourage a SACHRP formal initiative in this domain. IRBs take guidance very seriously… I don't think anyone is going to change on their own unless there's broad systemic change.”
Deborah Collyar, founder of Patient Advocates in Research, agreed: “We've been talking about these issues since I got involved in research 20 years ago. Now it's time for action.”