Virtual Clinical Trials Reality or Just Virtual Reality?

Approximately two years ago I was attending the plenary session of an industry conference where the speaker was a representative from the FDA.  After his talk there was the standard question and answer session and one of the audience members asked him how the agency viewed the veracity of “virtual trials” in support of NDA submissions.  I watched with interest as a veil of confusion descended over the speaker’s face as he requested additional clarification on the meaning of virtual trials. After some back and forth, there was a rudimentary explanation about conducting research outside of the investigative clinic, and his response was essentially to re-affirm the required involvement and responsibility of the investigator in seeing the research subject and then he quickly moved onto the next question.  The inescapable irony of all of this was that the program for this conference, as well as many others that year and in years to come, was riddled with the topic of virtual trials, how to run them, and anecdotes of pilot programs.

The term “virtual trial” has now made its way into the lexicon of contemporary buzzwords in the clinical research industry and in doing so, has perhaps muddied the waters as to the meaning and intent of what companies are actually trying to accomplish.  My colleague Ron Waife has often stressed to me and others that “terminology matters”, and in this case it is especially true.   Thus, it may be helpful to deconstruct the terminology from the intent, and then re-brand the outcome, so as to better discuss the definition, advantages and regulatory perspectives of this important trend.

Patient Recruitment & the Virtual Response

If you ask managers at most biopharma and device companies what their primary challenges are in conducting clinical trials, the one that consistently boils to the top of the list is patient recruitment.  That is, finding good study candidates in a relatively short time.  If one delves further into the challenges surrounding patient recruitment, much of the research performed to date points to two significant factors that directly influence enrollment, namely:

1) Protocol complexity

2) Subjects’ geographic proximity to study sites.

The intent of “virtual trials,” among other imperatives, was to address both of these concerns, especially the second one, by facilitating study visits either in the patient’s home environment or at a nearby “virtual” location by leveraging the use of telemedicine technology and third-party healthcare providers.   The suggestion is that by making the experience more convenient for a subject, we can increase their willingness to participate in a trial, even one with more demanding procedures.   And this is where the “virtual” terminology becomes confusing and problematic, as there is nothing “virtual” about this interaction!  Someone who works for a company that provides this type of remote visit service recently used the term “decentralized trials”to describe the approach, which I think is a more accurate term.

There is real credence and value to a decentralized trial, especially for certain visits which only require that rudimentary procedures to be performed, and a number of companies are racing to fill this need, as the evolution of technology and remote capabilities has far outpaced the regulations that were put in place many years ago. The problem is that when we use the term “Virtual Trial” with regulators, a cold shiver justifiably begins to descend down their spines as they envision a situation where investigators never actually see or interact with subjects and physical clinics are non-existent, or worse.

Virtual Trial as in Something Else Altogether

What if there are no subjects or investigators at all? A number of talks and articles have been presented advocating for these types of trials, where the entire trial is conducted within an artificial intelligence program that promises to leverage “real world data” to predict the safety and efficacy profile of a molecule by simulating how the human body would react.  This illustration is probably a more accurate use of the term virtual, but it is very different from our previous example, and while innovative in its purpose, poses a significantly higher hurdle to acceptance by any regulatory authority, especially for a new drug/device/biologic application.  The hurdle is justifiably high since our knowledge of the human body is still so insignificant after all these millenia, as the CEO of Novartis, Vas Narasimhan, recently opined at the JP Morgan conference: (https://www.forbes.com/sites/davidshaywitz/2019/01/16/novartis-ceo-who-wanted-to-bring-tech-into-pharma-now-explains-why-its-so-hard/#28569fec7fc4).

So, it is safe to say that we are not yet at the stage where “deep learning” or AI is going to impute for us the complete metabolic impact of a particular drug or biologic, based strictly on existing EHR and other real-world data.   In fact, the entire premise of AI is that it needs to have clean structured data in order to learn from, and with such large gaps in our understanding of current human physiology, the existing datasets are not complete enough to fill in those gaps.

On the other hand, there is significant advantage and value to the concept of decentralized trials, which with continued efforts and innovation, can result in greater access to patient populations in need of new experimental treatments.  This remote model may also serve to decrease the non-safety related dropout rates from clinical trials as convenience factors are improved.

Instead of hamstringing ourselves by using equivocal buzzwords, it may be worthwhile to consider using definitive terms to explain the concept of conducting clinical trial visits outside of the investigative site. So that we have more time to focus on the perceived benefits of non-traditional trial designs and methods. The German philosopher Arthur Schopenhauer probably said it best: “one should use common words to say uncommon things”.

Contact Steve Shevel, shevel@waife.com, to discuss this further.