"Innovative Treatment" vs Research: Which is It?

The following original article which I wrote and was published today at the bioethics.net website is reproduced here with permission.  I will put some additional comments as an Addendum at the end of the copy. ..Maurice.
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February 19, 2013 12:30 pm

“INNOVATIVE TREATMENT” VS RESEARCH: WHICH IS IT?

Maurice Bernstein, M.D.

When does a doctor’s treatment of a patient become medical or surgical research? If what the doctor does is a standard and accepted method of therapy using proven medications or surgical techniques and represents nothing novel then at first glance what is occurring cannot be designated as research or can it? Ah! But here is where the issue of “innovative treatment” versus “medical/surgical research” become clouded. The United States government has set a standard regarding what activities by physicians could be called research and what could not based upon the April 19,1979 Belmont Report summarizing a governmental commissions conclusions and set the ethical standards for the ethics of research. The standard of what is research is summarized in the IRB Handbook (1993)

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.

The government considered this distinction important because it would then separate physician activities carried out as a part of usual physician care of a patient from medical or surgical research. Such a distinction would then permit usual care to be free from government research oversight including institutional bodies known as IRBs (Institutional Research Boards).

For those readers unaware, IRB’s as described in Wikipedia:

An institutional review board (IRB), also known as an independent ethics committee or ethical review board, is a committee that has been formally designated to approve, monitor, and review biomedical and behavioral research involving humans. They often conduct some form of risk-benefit analysis in an attempt to determine whether or not research should be done. The number one priority of IRBs is to protect human subjects from physical or psychological harm. In the United States, the Food and Drug Administration (FDA) and Department of Health and Human Services (specifically Office for Human Research Protections) regulations have empowered IRBs to approve, require modifications in planned research prior to approval, or disapprove research. IRBs are responsible for critical oversight functions for research conducted on human subjects that are ‘scientific’, ‘ethical’, and ‘regulatory’.

It is apparent that an activity either being research or not being research can then involve or then not involve a host of governmental scrutiny and interference toward the physicians participating.

As you can read from the definition of research, the novelty of the treatment is not part of the criterion. The basic distinguishing characteristic that research is to be or is carried out is simply whether there was intent to collect data from that treatment and then formally present the data to others. It has nothing to do with whether the treatment was innovative or a standard medical or surgical practice. For example, a doctor finds through his or her reading or perhaps from a colleague that the off-label use of an established drug might be of value to a patient whom is not responding to the usual drugs prescribed.  Prescribing that drug without the intention to collect some patient data (such as an improvement in white blood cell count) in order to document the response as part of a communication of the value of the drug’s use to others by lecture or journal article would make this simply “innovative treatment” and not research. And the surgeon could be trying out on a patient a different approach in the procedure used to perform the operation and not documenting the apparent benefit or apparent complications of that procedure intentionally to be part of some formal presentation, then this could be considered only “innovative treatment” and not research.

Now, of course, the matter of informed consent by the patient would still apply and any complications from the off-label use of a drug or the non-standard operative procedure would still be the professional responsibility of the physician. But nevertheless, the government’s definition of research eliminates all the detailed disclosure requirements and safety precautions presumably part of the government’s  creation and utilization of IRBs.

So, what about the ethics of the separation of research from “innovative treatment”? Autonomy (the principle of self-determination by the patient) and Beneficence (the need to look toward doing good to the patient) should still be the paramount ethical principles in whichever activity is performed. I think that the following abstract from the American College of Obstetrics and Gynecology’s Ethics Guidelines sets the responsibilities of any physician who plans to veer away from common standards of practice as “innovative treatment” (whether medication, tests or procedures);

Innovations in medical practice are critical to the advancement of medicine. Good clinicians constantly adapt and modify their clinical approaches in ways they believe will benefit patients. Innovative practice frequently is approached very differently from formal research, which is governed by distinct ethical and regulatory frameworks. Although opinions differ on the distinction between research and innovative practice, the production of generalizable knowledge is one defining characteristic of research. Physicians considering innovative practice must disclose to patients the purpose, benefits, and risks of the proposed treatment, including risks not quantified but plausible. They should attempt an innovative procedure only when familiar with and skilled in its basic components. A clinician should share results, positive or negative, with colleagues and, when feasible, teach successful techniques and procedures to other physicians.  Practitioners should be wary of adopting innovative procedures or diagnostic tests on the basis of promotions and marketing when the value of the procedures or tests has not been proved. A practitioner should move an innovative practice into formal research if the innovation represents a significant departure from standard practice, if the innovation carries unknown or potentially significant risks, or if the practitioner’s goal is to use data from the innovation to produce generalizable knowledge. If there is any question whether innovative practices should be formalized as research, clinicians should seek advice from the relevant institutional review board.

My take: Though the separation between what is “innovative treatment” and research may still be a bit hazy for full satisfaction, to me it is how the physician, despite the government’s definition, behaves toward the patient defines the ethics to whichever activity is occurring and that is most important.
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Addendum:  I want to explain why I am concerned that the separation between "innovative treatment" and research is not as clear as I would like particularly for a professional action which could have far reaching effects in relation to its management, supervision and consequences.

 In the basic governmental document Code of Federal Regulations Title 45 Part 46 "Protection of Human Subjects", Section 46.102 (d) defines research as "Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. "

The IRB Guidebook then specifies research as "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" that it is "intent before treating" which is the defining criterion. It should be noted that this statement was an official IRB Guidebook answer  regarding the specific question: "Can treatment of a single patient constitute 'research'?" Since this definition is applied to a single patient, I assume that the definition applies to a dozen or hundreds of patients.  How is intent of the physician established and who decides  if not the physician him/herself?  And then what is "systematically collected data that would not ordinarily be collected in the course of clinical practice"?  I guess that is why defining what is research and what is not is really a matter of consensus.  What do you think?  ..Maurice.
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