Innovations in medical practice are critical to the advancement of medicine, but the question of “innovative treatment” versus “medical or surgical research” can often become clouded.  It was with great interest that I attended a breakout session on this topic at the 2018 Advancing Ethical Research Conference (AER18), led by Stephanie Cargill, PhD, and Jeremy Corsmo, MPH.

When does a doctor’s innovative treatment of a patient become surgical or medical research? This question comes up frequently and is also posed when research takes place outside the surgical theater. I was relieved to find out I was not the only person on the planet to have dealt with this issue. As the co-chair of an independent IRB, I see these scenarios often, and it is difficult to find someone with whom to discuss appropriate ethical and regulatory concerns.

The example given in the breakout session revolved around a physician at an institution with an institutional IRB:

• A study arrives for IRB review that is described by the investigator as a retrospective review of medical records to evaluate outcomes of a series of procedures conducted by a university clinician.
• The physician describes the procedure as standard of care as the physician performs this procedure regularly and the patient “would have had the surgery anyway.” Sounds like an exempt study, right? Not so fast…
• Upon review, it appears that the described procedures are not procedures conducted widely by the specialty, nor is there evidence of safety or efficacy data for this procedure in the published literature.

In the example, institutional officials, investigators, patient advocates, and IRB reviewers all came together to design a policy that stakeholders might reference while making decisions regarding the necessary IRB review level. 

Variations on this example are seen at independent IRBs who review studies submitted by surgeons in private practice. What guidelines should an independent IRB reviewer follow? I would like to share a couple of additional scenarios for thought: 

Case #1:

A doctor of chiropractic care in private practice would like to assess how the Bredesen Protocol alleviates health issues in patients with Alzheimer’s Disease.  The Bredesen Protocol has been described as a comprehensive lifestyle and nutrition approach to treating, and reversing, early-onset Alzheimer’s. The Protocol consists of a battery of dozens of lab tests, combined with interviews, home environment and life style considerations, assessments of sleep and social factors, testing for gut, mineral, and hormone imbalances, vast supplement regimens, and more. The chiropractor would like to prospectively prescribe this regimen to his elderly patients with Alzheimer’s Disease and compare results to an untreated cohort.

There are several ethical issues with this poorly designed protocol. There are too many variables. The use of over 40 supplements, hormones, etc. is dangerous in an Alzheimer’s (often elderly) population. In addition, it would be impossible to identify the component(s) responsible for any positive outcomes that might be seen in the study.

The Belmont Report states an activity is research “if there is a clear intent before treating the patient to use systematically collected data that would not ordinarily be collected in the course of clinical practice in reporting and publishing a case study. Treating with a research intent should be distinguished from the use of innovative treatment practices.” In brief:

• Whether the treatment is standard or innovative medical or surgical practice is irrelevant; and
• If there is intent to collect data and formally present those data to others, research is happening.

This difference separates actions carried out as part of a physician’s standard of patient care from other medical or surgical research—But what about the ethics of the separation of research from “innovative treatment”? Autonomy (the principle of patient self-determination) and Beneficence (striving to do good to a patient) should be foundational ethical principles in any activity performed. Consider the next case:

Case #2:

The same doctor of chiropractic care who would be “prescribing this regimen anyway as part of a patient’s treatment” would like to start a database where other physicians who have “prescribed this regimen anyway” may be invited to enter data from their previously treated patients. This would create a larger dataset that may be retrospectively reviewed so that more conclusive results might be obtained.

Doctors of Chiropractic care have access to a patient population who is open to, and often seeking, alternative care. The idea that practitioners across the US will be prescribing this regimen to numerous patients is not far-fetched.  A database to collect and compare regimens and outcomes might be useful to the 300 doctors across the nation who prescribed this protocol to 3 or 4 patients each.

It is important to differentiate between biomedical research, on one hand, and the practice of accepted medicine on the other, in order to know what activities should undergo IRB review. However, the distinction between research and practice is clouded partly because they regularly happen together and partly because the terms “experimental” and “research” are not consistently defined, understood, or utilized.

So, this brings me back to my original question, one that comes up often: what guidelines should an independent IRB reviewer follow? Can an IRB take an investigator at his or her word with regard to procedural innovations? Should an IRB automatically send any study like this up to the full board?  I’d love to hear others’ thoughts, comments, or suggestions on the subject and discuss this further. Comment below!

Gretchen Parker, PhD, RAC, CIP, serves as co-chair for Pearl IRB and provides regulatory and clinical research support services for clients. Throughout her career, she has been deeply involved in regulatory affairs, clinical research, and medical writing for the pharmaceutical and medical device industries.  She led the AAHRPP accreditation efforts at Pearl IRB and has assisted FDA inspectors on site. She is currently leading the efforts to update Pearl IRB institutional policies and procedures to comply with the revised Common Rule.

Dr. Parker began her career as a Regulatory and Compliance Analyst at a consulting firm, where she worked with clients, ranging from biotech start-ups to Fortune 500 companies, to plan and implement regulatory strategies, submissions, and research protocols.  Her duties engaged her with several US governmental agencies, including FDA, USDA and EPA.

Dr. Parker received a PhD in Molecular Endocrinology and Biochemistry from Purdue University, and completed her Post-Doctoral Fellowship in Biochemistry and Molecular Biology at the Indiana University School of Medicine Center for Diabetes Research.  She has authored and published dozens of scientific articles in major peer-reviewed journals, holds a patent for a diagnostic assay, and is a member of PRIM&R. She is Regulatory Affairs Certified (RAC) and a Certified IRB Professional (CIP).

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