I manage a small group of people.  I engage with colleagues.  I audit investigator sites around the globe.  I have worked for small companies and huge companies.  I have red hair. I have a few soap boxes (for those of you not familiar with the concept of a “soapbox”, I will endeavor to explain.  Google says it’s a term used metaphorically to describe a person engaging in often flamboyant impromptu or unofficial public speaking).  I see a trend in industry.

Let’s get a few basics out of the way, shall we say prerequisites.

1)     Clinical trial means studying a compound for use in, and by humans, for treatment of some medical condition.  To me, it makes no difference if this is a compound that is novel or is being expanded in some way (although I will admit the risks vary based on several factors, but for the purposes of this blog, let’s all just agree on this explanation).

2)     This trial is conducted by a physician or other qualified individual (e.g., dentist, psychologist, etc).

3)     Humans are not perfect, nor are we machines that divulge data without thought.  We can’t remember everything.  We have complex emotional feelings.  We have varying experiences and therefore perceptions. We can be influenced, biased, or coerced even without intention or malice.

4)     These humans are referred to as “subjects” for the purposes of this blog.

5)     Clinical trial subjects must meet the selection criteria because doing so maximizes the risk-benefit ratio for the subject and trial (as agreed by the governing Ethics Committee, Health Authority, etc.).  Part of this, also means that data collected from these subjects is also then “ideal” and will, in some way, benefit society as a whole.

Great, now that we’ve all agreed to these completely obvious prerequisites, I ask my question again.  What do you mean there is NO medical history for this subject?

Selection criteria for subjects are often not well defined by making statements such as “subjects with any other medical conditions that in the investigator’s opinion may affect the subject’s safety or ability to participate or comply with the trial requirements, should be excluded”.  But what this means is that the Investigator is so familiar with the subject that he/she can use their discretion to decide if the benefit-risk ratio will be compromised by involving this subject in the trial.  This does NOT mean that the Investigator is not aware of anything, nothing was documented by the trial assistants, or the subject has no visible reason for exclusion and therefore the subject should be enrolled into the study by default.

I propose that like the United States voyeuristic media, one is guilty until proven innocent.  Quality Assurance personnel have a mantra of “trust but verify” which is a nicer way of saying the same thing.  Therefore the conclusion is that Investigators should assume that subjects do meet the selection criteria unless documentation and personal knowledge of the subject indicates otherwise.

I will put a boundary on this blog to say that I am not going to go down the line of the physicians <dictum> to “do no harm”; but the thought did cross my mind.  I flew the above conclusion past a few really smart, authoritative, and mentally balanced people and astonishingly they thought I was cookoo (ah, once again allow me to translate….mentally ill) for thinking I had established a new requirement.

  • Dr. Toth-Allen from the US Food and Drug Administration was the second person I solicited an opinion from on my epiphany.  She agreed with my conclusion but added that the responsibility lies with the Sponsor (entity paying for the trial, the one who writes the selection criteria) to write detailed criteria.  These criteria must be sufficiently detailed to indicate what evidence (a document, an image, a verbal subject affirmation/denial, etc.) is required to fulfil each of the criterion.  Additionally, any limitations to the burden-of-proof shall we call it should also be written into the trial documentation by the sponsor.  A limitation might be “from medical record review of  the last 5 years” or “verbal discussion with the subject’s primary care physician (PCP), or documentation of three attempts made to solicit the information from the PCP”.
  • I suppose I should back up and tell you who I asked first.  Funnily enough it was a room full of healthcare lawyers at the SQA meeting in 2012.  Now, I do not know the number of people in the room that were actually lawyers, where the actual lawyers went to school or if they got good grades.  But, like every person that graduates from medical school, they are all called lawyer regardless if they were #1 or dead last.  Anyway, I digress a bit but I assure you there was a panel of lawyers seated in the front of the room.  I shared my conclusion with little explanation other than to report a recent experience at a dedicated research facility (meaning this facility conducted many trials and the physicians did not actively treat patients) and to my surprise the response was strong….no not strong…VIOLENT.  It was explained that treating a subject without any knowledge of them (medical history) was medical misconduct and I was encouraged to report any physicians using humans as subjects to their local medical board for ethical review.
  • A sponsor client responded to a finding in one of my audit reports around this topic with similar passion as me.  He asserted that it is a privilege to participate in research for those “selected” few.

Therefore, I ask all persons involved in research to seriously look into the practice of enrolling subjects in trials where no medical history is present.  I further declare that a subject’s verbal medical history reported at the first interaction is not sufficient medical history (see prerequisite 3) for enrolment.  Soapbox concluded (for now).

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