Clinical translation of cell therapies via medical innovation pathway

by Alexey Bersenev on January 24, 2013 · 0 comments

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There are two major pathways for translation of new biomedical technologies into the wide clinic. First is a clinical research, which implies conduction of trials. This pathways highly regulated by government agencies. The second pathway is a medical innovation, which led by physician and usually regulated by medical boards. Both pathways have advantages and disadvantages and both were consistently criticized in the recent discussions about regulation of autologous adult stem cells (AASC).

Jeremy Sugarman – Professor of Bioethics at John Hopkins University – wrote a very interesting opinion piece, where he overviews “stem cell-based innovation” pathway and expresses some concerns about it. I’m going to highlight his major points in this post.

Many practicing physicians and many patients in US are pushing forward translation of AASC as medical innovation without involvement of FDA. Their main arguments based on problems of clinical research pathway, such us: length of trials, huge cost and lack of funding, very selective enrollment. What are potential benefits of medical innovation pathway?

  • rapid (no “regulatory delays”);
  • captures patients with urgent medical need and patients which didn’t get enrolled in the trials;
  • could be publicly available and disseminated fast.

Further, Sugarman is asking: “What are potential harms of this pathway?”:

  • less comprehensive, therefore less protective for patients;
  • oversight is untested and not established;
  • may permit rapid “dissemination of ineffective and unsafe interventions”;
  • may compromise and delay clinical trials pathway.

The next question – what are barriers to implementation of stem cell-based innovation? He thinks that the main hurdle is the absence of clear oversight. There will be bunch of questions in establishing appropriate oversight for innovation pathway:

Who will assess the information provided by the innovator? What should be the qualifications of the reviewers? How will they manage potential conflicts of interest, both financial and non-financial? What should the review process entail, especially with an eye to distinguishing it from review of a clinical trial?

Yet another barrier is regulatory considerations. Medical innovation lacks of defining and may conflicts with FDA regulations. For example, FDA permits “expanded access” (“compassionate use”) of unapproved drugs, which could be quite similar to medical innovation pathway. Medical innovation should be clearly distinct from routine patient care and from clinical research:

… the lack of a definition of medical innovation that clearly disaggregates it from research will make it difficult for institutions to adopt a medical innovation pathway without risking the possibility of inadvertently violating federal research regulations.

Sugarman uses cord blood transplantation as an example of medical innovation pathway in successful translation of “stem cell-based therapy”. As a counter-example, he mentioned bone marrow transplant in breast cancer patients. Significant part of the article refers to ISSCR Guidelines for the Clinical Translation of Stem Cells:

While the ISSCR Guidelines emphasize the use of a research pathway for the clinical translation of most stem cell-based interventions, following an innova- tion pathway is permissible in limited circumstances for “a small number of…seriously ill patients.” Nonetheless, the innovation pathway under the ISSCR Guidelines involves an elaborate oversight process…

You can read oversight process recommended by ISSCR in the Guidelines. It is unclear whether physicians would (or should) entirely rely on ISSCR Guidelines in stem cell-based therapies translation or look for oversight via medical state boards as for surgical innovations. Yet another question – should both pathways be develop equally in translation of stem cell-based therapy? Suganman thinks that clinical research pathway should be used by default:

While it may very well be appropriate under certain circumstances for some aspects of clinical translation of stem cell research to follow an innovation pathway, there are myriad unanswered questions about doing so. Accordingly, the default pathway for clinical translation should be that of clinical research. However, if an innovation pathway is employed, there should be rigorous oversight, such as that recommended in the ISSCR Guidelines.

To conclude: both pathways can be used in clinical translation of stem cell-based therapy for patient benefit. But medical innovation pathway is currently required defining and appropriate oversight, otherwise it could be harmful for patients and could delay clinical translation. What do you think?

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