When (Real World) Data Won’t Do…

At a recent lunch --- perhaps signifying a resumption of routine business / social activity --- with an executive from a small biotech, after catching up on our respective family events over the past two years, we spent an hour or so reviewing the state of the pharmaceutical industry, organizational dynamics, technology, and the prospects for world peace (the final topic for which, regrettably, we could not generate a viable solution).?Having attended the DIA Annual Meeting last month in Chicago --- indeed, my emergence from my pandemic-induced fortress of solitude (!) has been generally limited to local forays --- I was fresh with pithy observations and perspectives that I took the opportunity to align (or not) with the actual experience of a clinical development leader with direct day-to-day responsibilities.?It was a refreshing discussion (and, of course, a welcome break from my home office (despite the loyal companionship of my four-legged son)).

Our conversation included a focus on the wonders of Real-World Evidence (RWE) and Real-World Data (RWD).?After agreeing that RWE would not be the solution for world peace, we focused in on the issues Clinical Development leaders face, particularly in responding to company (and investor) hopes that RWE/RWD could dramatically improve both the timing and cost of clinical development.?Clinical Development professionals --- a generally and appropriately conservative lot --- are increasingly expected to incorporate RWE/RWD solutions (and if one embraces the vibe from the DIA Annual Meeting) to the benefit of all parties.?

Don’t get me wrong: although RWE/RWD solutions may be outside the comfort-zone of many Clinical Development traditionalists, I’ve got an increasing volume of case studies demonstrating its benefits, ranging from use as a source of diverse patients (and sites) for clinical trials to use as a simulated control arm to use as the basis for an understanding of the natural history and progression of a particular disease.?Indeed, RWD can be an accelerant in clinical development and in getting an innovative solution to patients in desperate need.?BUT, RWD is not a panacea and may not be a solution to all development challenges.?Indeed, sometimes RWD won’t cut it…

We spoke specifically about the limitations of RWD in the development of products for neurological conditions (including pain).?While a RWD dataset could be useful in the identification of patients with a formal diagnosis (or even patients with certain characteristics indicative of a particular condition), we acknowledged that the management of these patients in actual practice would rarely include the battery of assessments required in a well-designed clinical trial.?Or if some assessments had been routinely undertaken, rarely would they have been performed on the same fixed schedule as prescribed in a clinical trial protocol.?While we noted that accessing the data --- grabbing the data from electronic medical records, for example --- represented an important and increasingly valued technological advance --- the value was modest, to say the least, if the data weren’t captured in the first place (and/or if the critical assessments weren’t routinely and consistently conducted).?Which caused me to invoke one of my favorite and cringeworthy baseball metaphors: RWD can get a runner on first or second, but that’s of little help if you need to score runs now.

Which led to a discussion of the “ball game” of drug development, approval, and market acceptance, and the time and place to (sorry) aim for the fences.?And yes, the power hitter may be more expensive to acquire, but when a home-run is needed, there’s no one I’d rather have in the batter’s box.?(OK, no more baseball metaphors, I promise).?But the important reality is that while RWD should always be evaluated, there remains a critical and valuable time and place and case for generating one’s own data through a prospective, real-world (non-interventional) initiative.?Each company’s development situation is different, of course, but as we dined, we discussed the value of imposing --- in a modest, “observentional” study sense --- various assessments that would fit reasonably elegantly within the real-world standard of care of managing patients with specific conditions, thereby generating information that could complement that being derived from controlled clinical trials and, importantly, that could represent a vital and on-going “asset” in the ultimate commercialization of the product.?The extra-base hit (damn! sorry) would generate RWE while nurturing important relationships with the patient and site communities.?And, perhaps, advance diversity and greater patient access along the way.

Over dessert, we concluded that RWD/RWE fills an important need in the overall (clinical and commercial) development game-plan (sigh.?sorry again), BUT that the plan needs to be customized to a company’s and to a product’s and a disease’s unique characteristics.?And to the potentially unique development pathway toward regulatory approval and market access. Our conclusion was that the first step is to actually have a plan, including rationalization and both internal and external expectation-setting for deriving and presenting evidence of efficacy, safety, effectiveness, and real-world value!?Know when to access and when to generate RWD.?Know to whom you’re presenting evidence and what matters to them!

It’s an exciting new age for clinical and commercial development, but the stakes are as high as ever.?For it’s One, Two, Three strikes you’re out, at the Old.?Ball.?Game.??