Stem Cell Therapies: Opportunities for Ensuring the Quality and Safety of Clinical Offerings: Summary of a Joint Workshop by the Institute of Medicine, the National Academy of Sciences, and the International Society for Stem Cell Research (2014)

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Moving Forward

Five major concepts seemed to have emerged from the workshop discussions, said Harvey Fineberg, president of the IOM: solving issues related to deceptive advertising; strengthening the scientific process to develop evidence of efficacy and safety; refining, reforming, or harmonizing regulation for stem cell therapies; respecting patient autonomy; and speeding the development and delivery of safe and effective treatments to patients. Fineberg asked speakers to consider these concepts or others while identifying what they see as the most important problems to address, what information they see as being needed to take action, and what actions are most important for moving stem cell therapies forward (see Box 6-1 for proposed ideas from individual workshop speakers).

WHAT IS THE MOST IMPORTANT PROBLEM?

Glenn Schattman of Weill Medical College noted that, as a clinician, his major concern is patient safety. “The first thing that I want to make sure is [that] something is safe before it is then brought to clinical trials to see if it is efficacious.” María de Jesús Medina Arellano from Universidad Autonoma de Nayarit also emphasized patient safety, but she mentioned in addition the need to maintain best practices within stem cell science. David Vladeck of the Georgetown University School of Law warned, however, against moving toward harmonizing global regulatory standards, arguing that this may constrain rather than spur the development of new products.

Timothy Caulfield of the University of Alberta agreed that safety is critical but also pointed to efficacy. Evidence is currently lacking that stem cell therapies are effective against the kinds of diseases being referred to on websites. Strong statements are needed regarding the current lack of evidence for effectiveness, he said. Gil Van Bokkelen, CEO of Athersys, Inc., agreed that compelling evidence of therapeutic effectiveness has generally not been delivered by the field, and he said that this is one reason why large pharmaceutical companies have held back from significant investment.

A better relationship with regulators is also needed, Van Bokkelen said. Companies are trying to develop therapies for serious unmet medical needs, and constructive engagement with the FDA and other regulators is needed in order to accelerate the pace of development of novel therapies. There is much ground for optimism, Van Bokkelen stated. The FDA has endorsed and is helping to create new regulatory frameworks and streamlined approaches to enable the rapid development of effective therapies. Addressing these needs could have enormous consequences, both economically and medically, for national health care systems.

Michael Phelan said that he would like to see more balance in the information that is being presented to patients, rather than just the possibility of bad outcomes. “What is the truth [about the] positive things that are happening in this market and how can you help patients interpret that?” Clinics that have good laboratory practices, that are helping patients, and are publishing their results could be identified and certified.

However, if governments, regulators, and scientists are simply trying to shut every clinic down, patients will view them as part of the problem rather than part of the solution.

WHAT NEEDS TO BE KNOWN?

Van Bokkelen raised the issue of the size of the stem cell clinic industry and its potential impacts. Rough calculations would suggest that hundreds of millions of dollars are being spent annually on stem cell treatments, he said. The impact of those expenditures on both health and personal finances is unknown, in part because institutions are not obligated to report on and are not voluntarily monitoring the impact of the treatments they are delivering. Arellano agreed that clinics and other enterprises should voluntarily give information to regulators that they gather from patients.

A family with a desperately sick child may be tempted to take college education savings and spend that money on an unproven stem cell therapy instead, Van Bokkelen continued. The therapy may not pose a clinical risk, but it does impose an economic harm on that family, he said. However, the needs of patients and their families cannot be ignored. R. Alta Charo of the University of Wisconsin–Madison added that physicians and the scientific community do not fully appreciate the needs and desires of patients. “Some people want to keep trying things until they are proven to be a bad idea as opposed to waiting until it is proven to be a good idea.”

Charo called attention to the need for good information and honest brokers to convey information to patients and physicians. In particular, patients lack the context and explanation they need to understand the outcomes of many of these clinical trials. The professional community needs to speak in lay terms so that patients can engage with the information they provide, said Ellen G. Feigal of the CIRM. Also, as has been seen with warnings about the hazards of tobacco, information about the harms of an activity does not necessarily lead individuals to decide to avoid or stop that activity. Communication is part of the solution, but only part.

Charo also emphasized the need for trust among the groups involved in the stem cell field. A lack of trust regarding the intentions, motivations, and honesty of the different groups involved can be an obstacle to progress. Bringing groups together would help to overcome that obstacle.

WHAT COULD BE DONE?

Phelan advocated focusing on what is working instead of instances of malfeasance. An organization should be collecting positive information and helping patients. “The most productive thing that could be done is to help patients sort through the clinical trials that have shown efficacy.”

Certifying clinics would be another way to help patients make decisions on receiving stem cell treatments, Phelan said. Schattman agreed that certification or accreditation of clinics would be very helpful. In addition, requiring clinics and other organizations to submit outcomes data to a central organization would help produce the information that patients and regulators need.

Feigal pointed out that international professional societies could set guidelines for the field. The mission of regulatory bodies is to advance innovation in addition to protecting patients, and guidelines could help achieve a better balance. Efforts by governments to investigate the efficacy of complementary or alternative medicines also could be directed toward the study of stem cell therapies, she said.

Amy Rick, CEO of Parkinson’s Action Network, pointed to the value of patient organizations as a source of information for patients. Patients trust these organizations and often turn to them for assistance. But these organizations need support from professionals to work on issues of common interest.

Caulfield pointed to the need for a source of information on the state of the science for patients that is truly independent. However, information about the nature of clinical trials would also need to be included, particularly given that trials have a high failure rate and results are difficult to replicate.

Truth in advertising is also important so that patients are not misled, Caulfield said. Vladeck noted that consumers are getting a mixed message from the scientific community. On one hand, stem cells are touted as the next breakthrough therapy. On the other hand, patients are told that current therapies do not work, which is “a hard message for most consumers to digest.” Clinicians can play an important role in helping to inform patients when they come in asking about these clinics, Caulfield said (Levine and Wolf, 2012).

Irving L. Weissman of the Stanford University School of Medicine pointed out that no single country can solve this problem because the entities can move across national borders. The solution also has to in-

volve not only trials overseen by IRBs and FDA-like regulations but medical licensure and regulation of false advertising.

If issues are occurring, complaints can be filed not only by patients but also by their home physicians, Vladeck said. “Where are the people who were involved in the care and treatment of patients before desperation set in and they were forced to go elsewhere?”

Van Bokkelen argued that the United States is “long overdue for the development of a coherent national strategy and a national [or international] initiative” on stem cell therapies. It could marshal expertise and pool resources to drive the development of the field, he said.

A CONTINUED DIALOGUE

In his closing remarks, Fineberg emphasized the opportunity for a higher order of collaboration across the scientific, clinical, and patient communities. Continued dialogue and a clearer definition of needs could hasten the arrival of demonstrably effective stem cell therapies, he said. “The onus is on us in the scientific and health communities to enlist the patients, to enlist the clinicians, to persuade the funders, and to get on with the business of accomplishing what the promise of stem cell research has held from the very beginning—successful treatment.”

Ralph Cicerone, president of the NAS, pointed to the value of dialogue. Every stakeholder represented at the workshop has valid and well-intentioned concerns, he said, yet each stakeholder represents just part of the picture. “As people try to figure out where to go next, guidance from the discussion today and the dialogues that have started are really going to be valuable.”