ICMS Conclusions & Requirements to RNLBio
Findings and Recommendations from the Investigation of RNLBio
In October of 2010, the International Cellular Medicine Society (ICMS) learned of the deaths of two patients who received medical treatments using adult autologous stem cells (A-ASCs) harvested and banked by RNLBio, a company focused on development and commercialization of adult stem cell therapeutics based in Seoul, Korea. The two patients had received intravenous stem cell infusions using the patients’ own fat- derived stem cells for generalized “anti-aging” therapy in Japan and China.
RNLBio participates in the ICMS Treatment Registry, a web-based database that tracks safety and outcomes of patients that have received A-ASCs. RNLBio offers cell based medical treatment for a number of indications, ranging from anti-aging to autoimmune hearing loss. The ICMS has contracted with RNLBio to provide proactive tracking of patient reported outcomes for three conditions that comply with the ICMS criteria for Registry participation (critical limb ischemia, osteoarthritis and Parkinson’s disease).
While the two patients above were not ICMS Patient Registry participants, the cell processing and other procedures involved are common to all RNLBio patients. When the ICMS was made aware of reports of the patient deaths the Society had an obligation to carry out an investigation into the cause of death of the patients and to examine RNLBio’s treatment practices. ICMS sought and obtained RNLBio’s cooperation in investigating the causes of the deaths and potential interrelationships between RNLBio practices and the patients’ deaths. ICMS initiated its investigation of RNL Bio on November 11, 2010. The resulting adjudication provided these findings:
The death of patient 1, which occurred nearly 2 months after his last stem cell infusion, was unlikely to have been caused by either the stem cells or the procedures used to administer the stem cells. The specific cause of Patient 1’s death is currently unknown as no documentation has been released with this information.
The death of patient 2, which occurred on the same day as the stem cell procedure, was likely to have been caused or triggered by the stem cell procedure. The cause of death was due to a pre-existing blood clot that traveled to the lungs, and may have been precipitated by the procedure used to infuse the stem cells, or less probably, from a clot formed by the cells.
Upon review of these findings, the ICMS notes critical compliance issues and makes recommendations to RNL Bio:
I. Findings as to Compliance with ICMS Guidelines
The ICMS finds that RNLBio and/or its partners are engaged in practices that are not consistent with the Clinical Guidelines of ICMS. The specific ICMS guidelines relevant to this case are:
- ICMS Clinical Guidelines, Chapter 2, Section A: A physician must conduct comprehensive assessment of the patient prior to donation which includes:
- History and physical examination specific to the problem being considered for treatment
- Assessment of general health status and ability of the patient to participate safely in the A-ASC therapy
- Discussion with the patient concerning the risks and benefits of the planned A-ASC procedure
- ICMS Clinical Guidelines, Chapter 2, Section C: The ICMS considers the following to be basic tenets of clinical translation:
- All research protocols using investigational cell lines should be approved by an Institutional Review Board.
- ICMS takes no position on how research is funded and due to the dire need for treatment options for patients approves the use of “pay for trial” type research.
- A blinded standard is not necessary. However, there should be measurement of both clinical outcomes and objective imaging or other objective changes.
- ICMS Clinical Guidelines, Chapter 2, Section J: The physician should use very effort to prospectively grade each A-ASC therapy candidate into candidate categories, such as Good, Fair, or Poor. While scientific data on candidacy grading may or may not be available, oftentimes pragmatic grading systems can be used until such data becomes available. This grading should therefore take into account:
- Objective indications of disease severity: For example, a patient who has more severe disease may be less likely to respond than a patient with mild disease.
- Co-morbid conditions: For example, a cardiac treatment may be less effective in a patient with significant co-morbidity such as COPD, type I diabetes mellitus, and PVD.
- Patient history: For example, a patient with a history of severe osteoporosis may be less likely to respond to a fracture healing application.
- Prior physician experience with response rates: For example, the physician may have experience that a cosmetic application is less likely to be effective in patients over 80 years of age.
- Contraindications: For example, the patient may have a history of active malignancy.
- Factors that may reduce outcome: For example, the patient may be taking medications that negatively impact A-ASC yields.
While RNLBio appears to be out of compliance with ICMS Guidelines referenced above, of greater concern is the question of whether RNLBio is practicing medicine or engaging in the processing, banking, and provision of cells to treatment clinics. Under Korean law, RNLBio cannot engage the implantation of stem cells unless done under the auspices of Korean Food and Drug Administration (KFDA)-approved clinical trials. With the exception of these clinical trials, RNLBio does not itself, and legally cannot provide infusion of cells in South Korea. To provide treatments, RNLBio instructs patients to arrange a visitation to affiliated medical organizations in China and in Japan. It is within these clinics that patients receive treatments of their own A-ASCs that have been obtained and processed by RNLBio. This interruption in the oversight of the cells and outsourcing of treatment to third party clinics appears to lie outside of the establish norms of the practice of medicine.
II. Compliance Requirements for RNLBio
The International Cellular Medicine Society formally demands that RNLBio implement the following compliance requirements for all patients receiving treatments with cells harvested, processed, banked and provided by RNL Bio in accordance with ICMS Standards and Guidelines:
- Initiate the process of formal clinic accreditation established by the ICMS within 30 days.
- Demonstrate compliance with the best practice guidelines established by the ICMS, including, but not limited to:
- Development and universal use of an institutional review board approved informed consent for enrollment in any clinical trial or treatment using A-ASC’s.
- Universal use of ICMS patient candidacy evaluation procedures,
- Pre-operative evaluation of all patients seeking treatment.
- Initiate comprehensive program for the management of patient records, including the collection and tracking of patient medical history and outcomes.
- Develop an Ethics Oversight Group to assess the quality of informed consent given to patients.
- Provide proof that RNLBio Patient Coordinators, ‘Codi’s, act solely in the capacity of patient coordinators, and thus engage with patients only within a system in which all potential patients who indicate that they seek to utilize their cells are examined by medical doctors prior to banking of any cells or extraction of any material for banking.
- Provide Patient Coordinators with annual training and that such training should include bioethics as well as an examination as to competency.
- Submit itself to a full and complete audit by the ICMS of its practices and the adoption of these recommendations within 90 days of the publication of these findings.
- Institute a process to ensure that all procedures that utilize cells harvested and/or processed by RNLBio are delivered to patients in accordance with ICMS guidelines and establish an indemnification clause in RNLBio contracts to delineate the ethical and legal responsibility of each party in delivery of these cells in accordance with ICMS guidelines.
- Come into compliance with international standards for the practice of medicine by maintaining the one-on-one relationship between physician and patient.
Over the next 90 days, the ICMS will evaluate the practices of RNLBio and provide RNLBio with guidance on how to enter into compliance with ICMS guidelines. Should RNLBio fail to comply with the above guidelines and recommendations within 90 days, the ICMS will be forced to terminate RNLBio’s participation in the ICMS Treatment Registry and suspend its membership within the Society.