Blogging today’s FDA stem cell meeting: Part 2 Clinics, Policy & Ethics

The FDA is holding its first 2016 stem cell meeting today and you can read about some impressions of the morning session of this meeting here.

In this post, I’m focusing on the afternoon session, which has been mostly on policy and ethics, including on stem cell clinics.jonathan-kimmelman-fda

Jonathan Kimmelman from McGill University got the afternoon going with his excellent talk “Ethics, Evidence, and Regulatory Approval for Cell-Based Interventions“. Jonathan started his talk addressing the stem cell clinic situation in the U.S. and asking more broadly how regulatory authorities should establishment a benchmark for making experimental interventions such as stem cells available to patients.

He asked if there is a zero sum game between innovation and oversight? He argues there isn’t. They can actually work together. With oversight you maximize the amount of data per patient put at risk.

He used gene therapy taking decades (and still no approved therapy) as an example of the timeline for experimental stem cell therapies.

What about the idea of patients vs. bureaucracy? Is that a genuine dynamic? Are the most vocal patients democratic representatives of patients more generally?

jonathan-kimmelman-stem-cell-clinical-translation-talk

jonathan-kimmelman-stem-cell-clinical-translation-talk slide

In talking about the idea of safety vs. efficacy, he discussed risks of cell therapies.

He asked, “How do we as a society want to distribute the costs and burdens of medical uncertainties?”

How does this all tie in with the new 2016 ISSCR guidelines on stem cell clinical translation?

Key issues include the primacy of patient welfare and social justice. There should not be exposure of patients to unproven therapies outside of true clinical trials or in other unique circumstances (I’m thinking expanded access).

Jonathan also talked about concerns with pay-to-participate trials for stem cells.

Above is a summary slide from Jonathan’s talk.

stamina-stem-cell-protocol-problems

stamina-stem-cell-protocol-problems

Massimo Dominici, MD next gave his talk “Dissecting Unproven Cellular Therapies: The International Society for Cellular Therapy (ISCT) Position.”

Dr. Dominici talked about global stem cell clinic locations, the costs, and the global challenge here. He showed data from the important John Rasko Cell Stem Cell paper on global stem cell clinics. He also cited the example of the Stamina problem in Italy and the “weird” protocols involved there in that treatment. One patient died. See his slide above on Stamina, where UCT means unproven cell therapy. To sum up he indicated that a problem is confusion between unethical versus innovative cell-based approaches.

Peter Rubin, MD wrapped up the session on  “Clinical Adipose-Based Therapies.” Dr. Rubin is a plastic surgeon who studies adipose (fat) stem cells. He talked about autologous fat transfer versus adipose stem cell treatment. As to the former, he discussed the strong safety profile and good results with fat transfer outcomes (for instance with facial deformities from wartime injuries). There’s about 63% retention of volume induced with fat transfer in their experience. He reported that the # of cells in the fat tissue correlates with better outcomes. Tissue remodeling (not just volume) occurs. He did also mention how fat stem cells might be able to promote cancer recurrence or progression.

What about adipose stem cell treatments? Rubin called the basis for this as being “bioactive” cells from fat or the stromal vascular fraction, which someone from Wisconsin he says apparently calls colloquially “sushi”. I’m not sure I get that. Rubin uses an automated machine to make SVF. Lots of heterogeneity in SVF cell types. He talked about IFATs (a federation for fat tissue/cells). These cells make growth factors. They are using these cells in pre-clinical studies now (e.g. in rodents). Their clinical strategy under an IDE is to mix the SVF with the fat graft for traumatic amputation. He advocated for taking a responsible, evidence-based approach.

Overall, I found these talks to be really fascinating together linking together real-world experiences with stem cells in clinical use (responsible or not or even in the middle gray zone in some cases depending on one’s perspective) along with ethical and policy considerations as well as guidelines.

Wait, there’s an FDA stem cell meeting this week too? The scoop

stem cell crystal ball

Stem cell Crystal Ball

There’s a big FDA stem cell meeting coming along next week that has gotten much attention, but many people didn’t realize there’s also an FDA meeting on stem cells this week too in three days on September 8th.

I pasted this week’s meeting schedule at the bottom of this post from the FDA page. The meeting is a workshop entitled, “Public Workshop: Scientific Evidence in the Development of Human Cells, Tissues, and Cellular and Tissue-Based Products Subject to Premarket Approval”.

The meeting next week on September 12-13 getting all the attention is entitled, “Draft Agenda: Part 15 Hearing: Draft Guidances Relating to the Regulation of Human Cells, Tissues, or Cellular or Tissue-Based Products”.

Within the “Human Cells, Tissues, and Cellular and Tissue-Based Products” or HCT/P larger category the ones getting the most attention are stem cells. If you look at the speakers at this week’s meeting including the keynote by Irv Weissman, it’s pretty clear this meeting is focused squarely on stem cells even though it could apply to other products.

What’s the difference between the meetings?

Continue reading

Huge clinical trial patient fees allowed by FDA at times, details often secret

stem cell monopolyI am often critical of for-profit stem cell clinics on this blog for numerous reasons. For instance, one thing that concerns me greatly about these clinics is that they charge patients to get experimental “treatments” that have not been proven to be safe or effective.

But as some patients have pointed out to me over the years, certain FDA-approved stem cell clinical trials also charge patients to receive unproven stem cell therapies.

Should someone (even if that someone is an academic clinical researcher) be able to charge a patient a large access fee to be in a clinical trial in which that patient will be subject to an experimental therapy that could ultimately be proven unsafe and ineffective?

I have serious doubts about this.stem cell monopoly quote

You might be surprised to learn that the FDA in some instances allows patients to be charged to be in trials including stem cell trials and others. Those running the trials can request permission from the FDA to charge patients. The agency then has to evaluate the request. The FDA has a draft guidance on this, but frankly it’s difficult to learn that much from that document in terms of details in how this plays out.

Continue reading

ISSCR Releases Flood of Stem Cell Policy Docs

A committee of the International Society for Stem Cell Research (ISSCR) did one heck of a document dump yesterday on stem cell policy, releasing a whole bunch of policy recommendations on stem cells and more.

The torrent from ISSCR included a 37-page policy statement itself as well as several papers in top journals including the Lancet, Science, and Nature.

This output was the product of the members of a special  ISSCR Task Force, whose members I have listed at the bottom of this post. Who are the members? These are knowledgable, extremely bright people who care deeply about the issues.

ISSCR Policy Guidelines 2016

The stem cell policy positions of ISSCR and those in the associated publications were wide-ranging, touching upon everything from avoiding stem cell research hype to policies on human embryos to CRISPR of human embryos to three-person IVF/mitochondrial transfer, to clinical trials generally to patient-funded trials and more.

Continue reading

NAS proposes prudent US policy on 3-person IVF

3-parent babyA new report from the National Academies of Sciences, Engineering, and Medicine here in the US recommends a policy significantly more cautious on first read for 3-person IVF than that in place now in the UK.

My initial take on this new 164-page report is that it is very well thought out and the recommendations are both appropriate and prudent. I’m still reading the report so it is possible I may feel differently at the end or that others may point out concerns that I missed, but so far my impression is positive.

Keep in mind that 3-person IVF also goes by the monikers mitochondrial transfer, 3-parent IVF, and mitochondrial replacement therapy (MRT, the term used by the Academy).

Alta Charo Mito TransferNotably, the Academy committee explicitly stated that MRT is a form of human genetic modification and human germline therapy. Some proponents of MRT in the UK and even in the US had mysteriously claimed otherwise.

While the Academy committee wrote in the report that 3-person IVF is ethically permissible in theory, in practice the depth of their concern about the risks of this technology was reflected in the array of conditions that they detailed must be met first.

These conditions include, but are not limited to the following as taken in some cases verbatim from the report or the Academy press release:

  • initial MRT clinical investigations should be limited to women who are at risk of transmitting a severe mitochondrial genetic disease that could lead to a child’s early death or substantial impairment.
  • Only male embryos should be permitted to be used for pregnancy. This would avoid transmission of the donor mitochondria should something go wrong.
  • initial safety is established and risks to all parties directly involved in the proposed clinical investigations are minimized, although minimizing risk to future children should be of highest priority; (note, my interpretation of this is that more preclinical data are needed)
  • the likelihood of efficacy is established by preclinical research using in vitro modeling, animal testing, and testing on human embryos as necessary;
  • if the intended mother at risk of transmitting mitochondrial disease also desires to carry the pregnancy, it is determined by professional opinion that she is able to complete a pregnancy without significant risk of serious adverse consequences to her health or the health of the fetus;
  • clinical investigations are limited to investigators and centers with demonstrated expertise in and skill with the relevant techniques; and
  • FDA has reviewed the science surrounding matching the mitochondrial DNA subtype of the egg provider with that of the intended mother and if compelling, has considered such matching as a means of mitigating the possible risk of incompatibility that could arise from combining the egg provider’s mitochondrial DNA with the nuclear DNA of the intended mother.

I’m largely in agreement with the Academy on this policy recommendation. It seems wise and frankly more appropriately cautious based on the science than what is now allowed in the UK.

The policy recommendations were summed up by the committee Chair in this way:

“In examining the ethical, social, and policy issues associated with mitochondrial replacement techniques, we concluded that the most germane issues could be avoided if the use of these techniques were restricted by certain conditions, rather than prohibiting them altogether,” said Jeffrey Kahn, chair of the committee and the Robert Henry Levi and Ryda Hecht Levi Professor of Bioethics and Public Policy at The Johns Hopkins Berman Institute of Bioethics in Baltimore.  “Although MRT would not treat a person with a mitochondrial disease, its pursuit could satisfy prospective parents’ desire to bear genetically related offspring with a significantly reduced risk of passing on mitochondrial disease.  The limitations on MRT that we propose focus on protecting the health and well-being of children born as a result of the techniques.”

Now it will be interesting to see how and to what extent the FDA implements these policy recommendations as well as the response in the scientific community. I would predict that some proponents of MRT may view this policy as too restrictive. Perhaps some might interpret it as a green light, but so far in my reading I don’t see it that way.

The other fascinating thing is to compare this report on 3-person IVF to the organizer’s closing statement from the NAS Meeting on Human Gene Editing from December. Some of the issues raised in the new report on 3-person IVF seem to directly apply to human gene editing as well.

I appreciate that the committee was cognizant of larger issues such as transparency, access, and public discourse.

Here is the committee roster.

Jeffrey Kahn, Ph.D., M.P.H. (chair)

Robert Henry Levi and Ryda Hecht Levi Professor of Bioethics and Public Policy Berman Institute of Bioethics

Johns Hopkins University

Baltimore, M.D.

Jeffrey R. Botkin, M.D., M.P.H.

Chief

Division of Medical Ethics and Humanities, and

Professor of Pediatrics

University of Utah School of Medicine

Salt Lake City, U.T.

David Chan, M.D., Ph.D.

Professor of Biology

California Institute of Technology

Pasadena, C.A.

R. Alta Charo, J.D.1

Warren P. Knowles Professor of Law and Bioethics

School of Law and Department of Medicine and Public Health

University of Wisconsin at Madison

Madison, W.I.

James F. Childress, Ph.D.1

University Professor and John Allen Hollingsworth Professor of Ethics

Department of Religious Studies

University of Virginia

Charlottesville, V.A.

Alan H. DeCherney, M.D.1

Associate Clinical Director and Branch Chief

Intramural Program in Reproductive Endocrinology and Gynecology

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institutes of Health

Bethesda, M.D.

Marni Falk, M.D.

Assistant Professor of Pediatrics

Division of Human Genetics

Children’s Hospital of Pennsylvania

University of Pennsylvania Perelman School of Medicine

Philadelphia, P.A.

 

Jonathan Kimmelman, Ph.D.

Associate Professor in Biomedical Ethics

Biomedical Ethics Unit

McGill University

Montreal, Canada

Anna C. Mastroianni, J.D., M.P.H.

Professor

University of Washington School of Law

Seattle, W.A.

Vamsi K. Mootha, M.D.2

Investigator

Howard Hughes Medical Institute, and

Professor of Systems Biology and Medicine

Harvard Medical School

Boston, M.A.

Laurie Strongin

Founder and Executive Director

Hope for Henry Foundation

Washington, D.C.

Keith Wailoo, Ph.D.1

Townsend Martin Professor of History and Public Affairs

Department of History

Woodrow Wilson School of Public and International Affairs

Princeton University

Princeton, N.J.

STAFF

 

Anne B. Claiborne J.D., M.P.H.

Responsible Staff Officer

Rebecca English, M.P.H.

Program Officer

Morgan Stathem, M.S.

Associate Program Officer

Michael Berrios

Senior Program Assistant

_________________

1Member, National Academy of Medicine

2Member, National Academy of Sciences