Ubaka Ogbogu, LLB, BL, LLM Adjunct Associate Professor of Law

1. Beyond evidence and regulation: Medical tourism and the direct-to-consumer marketing of stem cell therapies Ubaka Ogbogu, LLB, BL, LLM Adjunct Associate Professor of Law Associate Director of Research and Education Consortium on Law and Values in Health, Environment and the Life Sciences & Joint Degree Program in Law, Health and the Life Sciences University of Minnesota

2. Outline • Media reports and examples of stem cell offerings • Research objectives/questions • Research methodology • Results • Conclusion • Current policy landscape

3. Stem cell cures: Ready for prime time? • Somatic stem cell research has reached the clinical trial phase for diabetes mellitus, MS, stroke, myocardial infarction, among others. • Therapies remain unapproved and unavailable outside of experimental trials due to knowledge gaps, technical challenges, and regulatory hurdles.* • Only one approvedhESC therapy clinical trial, currently on hold due to safety concerns.

4. Putative Stem Cell Therapies and Offerings “Our website is solely dedicated to providing you with up to date and on target information on stem cells, research and current treatments available in China” “If you are interested in getting more information about finding a treatment in China for a specific ailment, and you are in North America, you can call us toll free...”

6. Research Objectives/Questions • Review of media reports indicated that DTCA via the Internet plays an important role • Primary objective was to document and characterize a novel occurrence of DTCA • What sorts of therapies are offered? • How are they portrayed? • Is there clinical/scientific evidence to support the use of these therapies? • Are they regulated and in what way?

7. Study methods • Two prongs: • Content analysis of websites offering stem cell therapies • EBM-based analysis of peer-reviewed clinical evidence for primary human studies reporting clinical effects of any stem cell therapies* • Websites identified through media reports and Google searches (final sample:19) and coded for therapeutic offerings, indications, claims, benefits, risks, cost of therapy, evidence, location of clinic, etc. • Clinical evidence identified through comprehensive PUBMED search. 45 records met relevance criteria • Inter-coder reliability testing completed on random sample

8. Content analysis results: Stem cell types offered

9. Stem cell sources

10. Transplantation procedure

11. Treatment indications

12. Benefits vs. Risks Mentioned • All websites surveyed mentioned improvement of disease state as main benefit of treatment • 14 (74%) of the websites did not mention any risks • Few websites mentioned procedural risks, and nonspecific fever and tingling as only risks of procedure

13. Example statements • “Of over 1800 patients we have treated, we estimate that 85% have gotten some kind of improvement and 80% have been satisfied with the improvements that they have gotten. We by no means guarantee improvement, but ... we are extremely surprised when patients do not get improvement” • “Transplantation is a safe, painless procedure. It is conducted in a sterile environment by professional medical personnel” • “List of contraindications against cell therapy is rather limited. No negative side effects were observed”

14. Treatment portrayals • Indications scored very or somewhat unclear or indeterminate in 68% of sites (websites use catch-all categories like aging, ‘‘increased feelings of energy’’) • 12 of 19 websites has indications which spanned 4 or more broad disease categories • Benefits portrayed as somewhat or very relevant in 79% of websites • Risks portrayed as very irrelevant in 74% of websites • 17 of 19 websites portrayed treatments as routine or somewhat routine • Credibility established through numerous patient endorsements, patent claims, media reports, and publications

15. “We have proved that the efficacy of autologous stem cell therapy in minor spinal cord injury ranges from 45 to 70%. Here everything depends on the size of the lesion, the level of injury, and the years post injury. The best results were obtained in the patients with thoracic level of injury; 2-5 years post injury and incompleteness of SCI” – Neurovita.ru

16. Location

17. Clinical evidence study: Inclusion/exclusion criteria • Targeted indications mentioned 10 or more times in top 2 disease categories: neurologic & cardiovascular • MS, Parkinson’s disease, Stroke, Alzheimer’s disease, SCI, and autologous hematopoietic stem cell transplantation (AHSCT) for acute myocardial infarction (AMI) • 89 total records, of which 45 included. Excluded records were unavailable (1), duplicative, non-stem cell interventions, reviews, or non-English (2), or referenced no clinical outcomes • Study not focused on describing current state of stem cell medicine

18. Results • Evidence for stem cell therapies for SCI and stroke is generally underdeveloped: small size, low methodological quality (e.g., no control group), and uncertain, negative, or contradictory findings • No studies of stem cell therapy for Alzheimer’s or Parkinson’s • Some history of stem cell therapy for MS, but clinical outcomes are variable and ‘‘not obviously better than the natural history of patients with multiple sclerosis” • Treatment recommendations made on the basis of the reviewed evidence likely to be low grade • Treatments offered by websites generally unsupported by clinical evidence

19. Study Limitations • Publicly available information is not indicative of information actually shared with patients during clinical encounters • We did not analyze actual outcome data for particular clinics. Instead we showed that high quality supporting evidence is lacking • Bias from exclusion of non-English studies. However only 2 such studies were excluded

20. Conclusions • DTC portrayal of current stem cell medicine appears optimistic and unsupported by clinical evidence • Patients may not be receiving proper or accurate information, and are subject to inordinate risk and financial burden • Clinics may be contributing to stem cell hype • Tourism aspect complicates post-treatment monitoring, protection of patient rights and regulatory scrutiny

21. Current policy landscape • Supranational soft regulation and advocacy (ISSCR, JDRF Int’l, ALS Worldwide) • Statutory intervention through physician standard of care rules? • Physician’s duty to report abuse, neglect, or situations of risk under minor and incompetent adult welfare legislation • Truth in advertising rules (FTC) • Local regulation – stem cell clinics have been shut down by regulators in the Netherlands, Ireland, US • Lobbying by research community for stricter national regulation

22. Acknowledgments • Co-authors: Darren Lau, Timothy Caulfield, Tania Stafinski, Devidas Menon, Benjamin Taylor • Canadian Stem Cell Network • REMEDiE • Linda Hogle