Follow-up Ethical Review of RNL Bio

BIO-ETHICS INVESTIGATION

As a result of findings uncovered during the investigation into the patients’ deaths, the ICMS initiated an on-site evaluation of ethical and clinical practices of RNL Bio, conducted by Dr. Glenn McGee, John B. Francis Endowed Chair of Bioethics at the Center for Practical Bioethics. His findings are as follows:

The system that was examined from the standpoint of ethical issues included myriad scientists, clinicians, coordinators, physicians, nurses, etc. It revealed a rapidly changing structure in which the relevant shared activity—for which RNL Bio must be held responsible—is the banking and processing of human cells that donors intend to use in interventions. These interventions are conducted to specifications created by RNL Bio (but not by RNL Bio physician/scientists, or in RNL Bio-owned facilities) and involve MSCs cultured by the company.  Both patients interacted with each of these systems as well as clinical organizations, and that systematic process is addressed below.

Recommendations

RNL Bio has a responsibility, heretofore not formalized or (to the best of ICMS' knowledge) documented, to ensure that not only is all information regarding banking made known to those who bank cells, but also that prior to the banking of cells--or payment to RNL for any services--every patient from whom adipose tissue will be derived participates in an informed consent process that includes all risks and benefits (as best known given the scientific and clinical literature, and RNL's own records, without selective presentation) of the use of banked cells.

This consent must be obtained by physicians who are not themselves RNL employees, but are trained in the information identified about, as well as in bioethics with regard to, informed consent as regards innovative and translational clinical science.  Even though physicians removing adipose cells by necessity have medical training, those doing so for RNL Bio banking should be trained as well in general internal or family practice medicine, and if a patient comes for removal of adipose tissue but indicates during the consent to removal that they have primary diagnoses for which they sought to bank cells (and/or use such cells in some future procedure), said physician should refer the patient to a physician in the relevant specialty, who should note that the patient understands relevant issues concerning MSCs and the relevant condition.  A patient with no diagnoses requesting banking is one thing; consent for risks of obtaining cells are to be discussed in that context.  A patient with a diagnosis likely will require a referral for discussion of that condition and standard of care treatments in the specialty.

In other words, in every encounter in which RNL's subsidiary groups, partners, customer organizations, or individual customers request services involving cells that RNL cultures and multiplies for the ostensible purpose of eventual therapeutic or research use (or that could be used in such fashion), informed consent must henceforth be obtained not only for banking but with a comprehensive description of the uses to which the cells to be manufactured might be put by any organization to which RNL would be willing to ship such cells.  Such consent must include a comprehensive review of the risks and benefits, i.e., the ethical issues comprising any informed consent that would encompass all activities to which the cells would be put to use by those to whom RNL is willing to provide cells.

To that end, it is recommended that RNL extend its enhanced informed consent form, and its enhanced Codi training program, both of which were reviewed in this investigation, with the addition of ethics training for all those who obtain informed consent relevant to the obtaining or use of cells, any of whom must hereafter be physicians with a clinical relationship to the patient.  Such training must be performed by person(s) with training in bioethics (as specified in the guidelines for training in clinical ethics promulgated by the American Society for Bioethics and Humanities and embraced by all major global training programs in clinical ethics), and it should be the goal of RNL to develop within 12 months a bioethics group whose purpose will be to assess the quality of informed consent through periodic ethnographic study of the knowledge of those who have undergone consent.  The legitimacy of such a division should be judged by scholars in the bioethics disciplines in peer reviewed journals such as Hastings Center Report and its analog in Korean, Japanese and Chinese languages.

Within 24 months, RNL should have organized an external, international ethics advisory board to oversee and to some degree participate in the promulgation of ethics standards based on these experiences, and to oversee the aforementioned proposals.

Coordinators, what RNL Bio refers to as Codis, should engage with patients only inasmuch as patients are, prior to banking of any cells or extraction of any material for banking, examined and if necessary diagnosed by a physician qualified in the area of medicine most appropriate to their general health, such information to be maintained for the mutual benefit of patients and all clinicians and RNL Therapeutics, and to be protected by all ordinary and appropriate privacy standards.

The International Cellular Medicine Society will continue its requirement that RNL develop comprehensive records regarding the experiences of all those who have received cells cultivated by RNL Bio, and to develop standards that reflect and accommodate the scale and international complexities of gathering and maintaining such information in patients' and the public's interest, which are judged as well by peers in bioethics and other relevant disciplines, and must evolve as do the relevant areas of medicine and science.

Dr. Glenn McGee is the John B. Francis Chair at the Center for Practical Bioethics in Kansas City, Missouri.