In this letter to the editor, Leigh Turner (University of Minnesota) responds to Doug Oliver’s article titled ‘Patients need proof, not presumption’.
1Associate Professor, University of Minnesota Center for Bioethics, School of Public Health and College of Pharmacy; Minneapolis, MN 55455, USA
At the invitation of RegMedNet, I am replying to Doug Oliver’s response to statements I made about my article, “ClinicalTrials.gov, stem cells and pay-to-participate clinical studies”. In my opinion, Mr. Oliver’s criticisms do not address my article’s core thesis. As I note in my article, U.S. organizations are listing on ClinicalTrials.gov “pay-to-participate” stem cell studies that do not appear to fully comply with federal regulations. The businesses examined in my article do not have FDA-approved stem cell therapies, and the studies registered on ClinicalTrials.gov are not conducted under FDA reviewed and cleared Investigational New Drug (IND) applications, even though they appear to require INDs. Furthermore, studies that are supposed to be conducted with cleared INDs cannot charge study subjects on a for-profit basis.
1. The title of Mr. Oliver’s response is “Patients need proof, not presumption.” It isn’t clear why Mr. Oliver believes this title is a suitable label for his concerns about my article and the accompanying interview. My article identifies by name particular organizations that have listed pay-to-participate stem cell studies on ClinicalTrials.gov. It lists their studies and offers my detailed analysis of how these studies do not appear to fully comply with federal regulations in at least two important respects. In addition to identifying concerns about stem cell studies that are registered on ClinicalTrials.gov without FDA-reviewed and cleared IND applications in effect, the article summarizes numerous ethical and scientific problems associated with pay-to-participate clinical studies.
Given the substantial amount of evidence my article provides, Mr. Oliver does not offer a convincing explanation of why he finds this analysis presumptuous or insufficiently evidence-based. In general, he underestimates the barriers to publishing such an analysis in a peer-reviewed academic journal even when criticisms of specific businesses and studies are backed with evidence and argumentation.
Academic journals are typically wary of litigation, and articles that critique the practices of particular businesses and other organizations can generate responses that take the form of legal threats and other attempts to intimidate and silence. Indeed, the very possibility of such threats highlights the importance of publishing carefully researched articles and not engaging in hyperbole. My article provides evidence and critical analysis, and does not take a speculative, presumptuous, or hyperbolic approach to its subject matter.
2. Mr. Oliver rightly describes himself as an activist. He has played an important role in drawing attention to the challenges faced by individuals suffering from vision loss. He has also contributed to policy debates by emphasizing the role stem cell research can play in seeking treatments for eye-related diseases and injuries. I support involvement of patients, patient advocates, activists, and other parties in public policy debates about ethical, legal, and scientific standards related to stem cells and human subjects research. I am glad Mr. Oliver and other patients are contributing to public conversations about regulatory standards, talking to journalists and otherwise having their voices heard, and informing public debate. Public conversations about ethics, science, and regulatory frameworks related to stem cells and regenerative medicine need to be inclusive. However, I have serious reservations about the specific form Mr. Oliver’s activism has taken.
Public conversations about ethics, science, and regulatory frameworks related to stem cells and regenerative medicine need to be inclusive.
The “Stem Cell Ophthalmology Treatment Study (SCOTS),” registered and listed on ClinicalTrials.gov, charges study subjects $20,000 or more to undergo injections of autologous bone marrow-derived stem cells for various diseases and injuries of the eye. Mr. Oliver is among the individuals who have paid to participate in this study. While I am glad Mr. Oliver’s vision reportedly improved after his stem cell procedure, I am very concerned about the extent to which Mr. Oliver’s advocacy work has relied upon his personal experience of improved vision and does not adequately acknowledge or address the concerns of other individuals who paid to participate in this study and suffered what they describe as complications related to the stem cell procedure or who experienced complications or lack of therapeutic benefits in other pay-to-participate stem cell studies registered on ClinicalTrials.gov.
I hope Mr. Oliver’s future contributions to policy debates grapple with the criticisms expressed by patients and other critics of this study and other pay-to-participate stem cells studies that are registered on ClinicalTrials.gov. For instance, the women who were harmed as a result of undergoing stem cell procedures for macular degeneration at another business that had listed studies on ClinicalTrials.govshould be taken into consideration as well as the lawsuits filed by former patients against such businesses as the Lung Institute and StemGenextwo companies described in my article.
3. Mr. Oliver claims I display a “clear presumptive bias” because I argue that clinics list “studies” on ClinicalTrials.gov in an attempt to confer legitimacy on their business practices. Many businesses refer on their websites to the “studies” they have registered on ClinicalTrials.gov. It is also possible to find press releases that draw attention to companies’ ClinicalTrials.gov listings and suggest or state that the NIH “approved” such registered studies. Because ClinicalTrials.gov is run by the NIH and is well-regarded as a reliable, credible source of information about clinical studies, listing pay-to-participate stem cell studies on ClinicalTrials.gov does indeed help to confer legitimacy on businesses that engage in direct-to-consumer marketing of stem cell treatments, while also registering pay-to-participate “studies”.
This is precisely why businesses draw such listings to the attention of prospective clients when they issue press releases, promote ClinicalTrials.gov listings on their websites, or otherwise advertise their pay-to-participate studies. As a result, listings on ClinicalTrials.gov help legitimate and publicize highly problematic studies. Such listings serve to market studies to patients who then pay thousands or tens of thousands of dollars to enroll.
4. Mr. Oliver claims that “the numbers don’t add up”. He later writes, “The sky is still above us”, as though I am somehow supposed to be Chicken Little, erroneously claiming the sky is falling. As I state in my RegMedNet interview, ClinicalTrials.gov is “a terrific public resource”. Later, I note, “there is a real problem with ClinicalTrials.gov, even though it remains a valuable public resource and a collective good worthy of funding”. I remain committed to making both of those points. ClinicalTrials.gov is a valuable public resource. It is also sometimes misused and abused. In my article, I provide specific examples of problematic studies. I do not claim there are thousands of such studies or offer wild exaggerations about what I found when I searched for pay-to-participate stem cell studies.
5. As I mention in my interview, after concluding my research for the Regenerative Medicine article I found additional instances of studies that fit the category of pay-to-participate stem cell studies in which the ClinicalTrials.gov listings contain reference to the phrases, ‘patient-sponsored’, ‘patient-funded’ or ‘self-funded.’ Mr. Oliver wants to know how many such studies I found after I concluded the research for my article. As I state in my interview, “there are now two more ‘patient-sponsored’ stem cell studies apparently taking place within the U.S”.
6. Mr. Oliver states, “a small sample cannot establish a significant trend.” My article and interview identify problematic pay-to-participate stem cell studies. I identified specific study sponsors by name and also listed particular studies. I do not know how large Mr. Oliver believes this problem needs to be before it deserves scholarly analysis and public debate. I would like to emphasize that my study focuses only on U.S. pay-to-participate stem cell studies registered on ClinicalTrials.gov. International businesses have also registered such studies. Again, it is possible to discuss these problematic studies and call for better vetting of studies submitted to ClinicalTrials.gov while also expressing appreciation for ClinicalTrials.gov as a public resource.
ClinicalTrials.gov is run by the NIH and is well-regarded as a reliable, credible source of information about clinical studies
7. Mr. Oliver accuses me of “innuendo” because of a third category of study mentioned in my article and interview. The first category described in the paper consists of pay-to-participate stem cell studies in which the ClinicalTrials.gov study listings themselves reveal that study subjects are charged to enroll. The second category was more challenging to investigate because in this case evidence that study subjects are charged was found somewhere other than in the ClinicalTrials.gov listings. Company websites, interviews with company founders, newspaper articles, and other sources provided information that study subjects pay thousands or tens of thousands of dollars.
8. I listed those studies where there was evidence that study subjects are charged even though this information is not disclosed on ClinicalTrials.gov. In addition to the 11 clinical studies listed in Table 2 of my article, I found other examples of businesses that appear to charge study subjects to participate in studies involving administration of stem cells. However, these businesses were not as forthright as the organizations listed in Table 2.
As I mention in my interview: “Had I described these businesses there would have been at least ten more pay-to-participate stem cells studies listed in my article.” In the article, I note that such studies have been registered on ClinicalTrials.gov by “at least two additional U.S. businesses”. The interview and article accurately note that I found additional studies that appear to fit the second category of analysis in my article. However, since these businesses either try to conceal that they charge study subjects or are unforthcoming about this practice, I made the decision to exclude these businesses and studies from the list of organizations that charge study subjects to enroll in studies, but do not disclose this information in ClinicalTrials.gov listings. Sharing such information accurately captures what I found while I conducted research for my article.
9. Mr. Oliver once again accuses me of innuendo because of a statement I made concerning whether or not NIH officials understand how many pay-to-participate stem cell studies are registered on ClinicalTrials.gov. As the interview on RegMedNet states, “the tallies for businesses and studies would also be far higher had I included the many pay-to-participate studies registered by international ‘stem cell clinics’. I was interested in using U.S. federal regulations as a tool for evaluating the commercial practices of U.S. businesses but there are plenty of international companies that have registered such studies on ClinicalTrials.gov. Do officials at the NIH have any idea how many of these studies are in their database? I wonder.” I do indeed wonder about this question because of the number of international clinics that have registered pay-to-participate stem cell studies on ClinicalTrials.gov.
Patients and their loved ones need to be provided with real tools that they can use to protect themselves.
When these listings are combined with pay-to-participate studies registered by U.S. businesses, I am left with the question of whether NIH officials have a comprehensive understanding of how many businesses have registered pay-to-participate stem cells studies on ClinicalTrials.gov. NIH officials have been alerted to the fact that some companies are registering such studies on ClinicalTrials.gov. It is for this reason that the ClinicalTrials.gov website now has a disclaimer on its homepage. My article acknowledges this disclaimer while challenging its adequacy. I would like to think that if NIH officials had a better understanding of the number of pay-to-participate stem cell studies now listed on ClinicalTrials.gov, they would acknowledge that the disclaimer is insufficient and there needs to be better screening of submitted studies before they are registered and listed.
10. Mr. Oliver claims that “patients need and deserve more than a ‘wink and nod’”. I agree. Patients and their loved ones need to be provided with real tools that they can use to protect themselves. Physicians, stem cell researchers, health and science journalists, and other individuals also need to be alerted to problematic studies registered and listed on ClinicalTrials.gov.
I hope my article helps patients, their advocates, physicians, policy-makers, regulatory officials, and other parties to understand that some clinical studies listed on ClinicalTrials.gov have serious ethical, scientific, and regulatory shortcomings. Rather than addressing this topic in a superficial manner, I provided examples of such studies, identified their sponsors by name, and reviewed the various ethical, scientific, and regulatory problems associated with pay-to-participate stem cells studies. If Mr. Oliver wants to criticize my analysis he needs to deal with the many substantive issues it raises rather than claiming that it traffics in innuendo and hyperbole.
Read Doug Oliver’s original response to Leigh Turner’s interview, or read Leigh’s original paper here (exclusively free for RegMedNet members).
The opinions expressed in this article are those of the author and do not necessarily reflect the views of RegMedNet, Future Medicine Ltd or any of its affiliates.