Democratizing Clinical Research
New vectors of innovation
A recent piece from The Economist neatly sums up the chronic challenges that plague clinical research:
Many problems faced by trials are startlingly analogue. To test a whizzy new drug on people you need two things: the drug and the people. It is the second that is more problematic. Serendipity, not science, limits many trials. To be eligible for a new cancer treatment you do not merely need to develop cancer. You must do so near a hospital that is running trials, turn up on a month when they are accepting patients, and on a day when the research nurse can sign you up. Get cancer in the wrong place, month or day, and you lose the trial and the trial loses you. The system is “sclerotic” says Charles Craddock, a professor of haemato-oncology at Birmingham University. For trials to work they need a pipeline of people pouring through. Instead, they catch raindrops in cups.
Source: The Economist
“Decentralized” clinical trials have emerged over the past several years with the promise that some of these challenges can be solved by making trials patient-centric. The tl;dr on decentralized trials is that new technologies (e.g. remote data capture devices, telemedicine) enable trial participants to complete study activities wherever they are (i.e. from home) instead of having to travel out to study sites. This addresses a huge pain point; the average clinical trial participant today travels 25-40 miles to participate in site-based activities. Reducing friction for trial participants should have the effect of improving patient recruitment/retention, reducing costs and increasing research yield.
Constraints on traditional site-based trials imposed by the pandemic have accelerated interest and capital formation around decentralized trials. However, the scope of the nascent but growing discourse around decentralized trials - largely about how and where clinical trial activities are completed - understates the potential of this shifting paradigm to fundamentally change who gets to do clinical research.
Big, broad scope
What does clinical research look like in practice? The gold standard is the randomized controlled trial (RCT). RCT’s help prove that the thing you are doing actually works.
As for the scope of “clinical research,” it’s already broader than you might think:
Clinical research is a component of medical and health research intended to produce knowledge valuable for understanding human disease, preventing and treating illness, and promoting health. Clinical Research embraces a continuum of studies involving interactions with patients, diagnostic clinical materials or data, or populations in any of the following categories: (1) disease mechanisms (etiopathogenesis); (2) bi-directional integrative (translational) research; (3) clinical knowledge, detection, diagnosis and natural history of disease; (4) therapeutic interventions including development and clinical trials of drugs, biologics, devices, and instruments; (5) prevention (primary and secondary) and health promotion; (6) behavioral research; (7) health services research, including outcomes, and cost-effectiveness; (8) epidemiology; and (9) community-based and managed care-based trials.
Source: Clinical Research: A National Call to Action, November 1999
The boundaries of clinical research are sufficiently expansive to incorporate several disparate categories of stakeholders. And importantly, this surface area is growing rapidly as the aperture of what constitutes healthcare grows. Then why is it that clinical research today is dominated by a handful of stakeholders - academia, government and pharma/biotech?
The major barrier to entry for groups who want to perform rigorous clinical research is cost. The entities that presently dominate clinical research are those that can rationalize high costs via mandate (academic institutions/government) or via the anticipated commercial payoff of successful research outcomes (pharma/biotech).
Another barrier is know-how (which is pretty much a derivative of cost). You need someone in your organization who knows how to properly design and execute a trial. All of the people who know how to do that are concentrated in the institutions above, because those are the only institutions performing clinical research at scale right now.
But now, we are witnessing a confluence of trends that is working to chip away at both of these barriers.
Democratized tools
New hardware and software tools are reducing costs and bridging knowledge gaps across the clinical trial value chain.
The most critical disruption point is at the beginning of the value chain - study and protocol design. Study design informs basically every other component of the trial process. Most new entrants to research lack institutional knowledge around study design best practices, manifesting as the question of “how do we even get started?” Software platforms like ProofPilot (a recent Sopris Capital investment) are helping new entrants design study protocols with easy-to-use tools (think drag-and-drop interfaces). The impact could be akin to any number of “no-code” platforms that have turned people into citizen-developers/designers/content-creators. On the trial execution, data collection and reporting side, a number of companies like HumanFirst and Healthmode (recently acq. by MindMed) have emerged to provide digital endpoints which enable quantitative FDA-grade data collection, often leveraging the existing ecosystem of connected devices (e.g. Apple watches, fitness trackers).
With respect to patient recruitment and enrollment, it’s worth speculating that some new entrants to research may actually have advantages vs. research “incumbents” via latent connectivity into captive audiences. Some categories that come to mind are patient communities, companies that have cult-y followings, and healthcare “influencers.”
All told, the proliferation of these technological advancements will increase access to the ingredients necessary to cost effectively perform clinical research.
Wham bam thank u TAM
Coinciding with diminishing costs and execution difficulty, the ROI calculus of performing research is dramatically changing for companies on the periphery of traditional healthcare as they look to take a piece of the massive TAM in healthcare.
Domains that were squarely in the realm of the “consumer economy” are becoming relevant in discussions around whole-person health and social determinants. Food is healthcare. Fitness is healthcare. Transportation is healthcare. This is reflected in commercial activity in the market - e.g. some UnitedHealth plans offer 1 year memberships to Peloton, dozens of companies offer mindfulness app subscriptions as part of their employee benefits package, Apple is investing significantly to build healthcare use cases around its consumer products, Lyft announced a major expansion of its “Lyft Assisted” healthcare service, Canadian doctors are literally telling patients to take a hike as a form of treatment.
In short, a range of groups previously relegated to the category of consumer wellness / technology have healthcare use cases in their crosshairs. This shift materially changes the ROI of conducting clinical research. With research validation that their products and services improve health outcomes, lucrative B2B use cases and customers may emerge (e.g. selling care programs into health insurance payors).
Consider musculoskeletal care which is one of the largest spend categories in healthcare (~$400bn TAM). A lot of digital-MSK care players have offerings that have very similar user experiences to fitness content libraries, along the lines of something like AloMoves. A major difference is that digital-MSK players like Kaia and SWORD have clinically validated their platforms via research studies. However, it’s not a stretch (nice) to imagine that a study putting patients through daily mobility exercises from AloMoves could deliver the same kind of health outcomes that well-funded digital-MSK providers have reported in their own studies. Another example is how the perception of mindfulness apps like Calm and Headspace have changed as they have achieved clinical validation of their products (in addition to greater acceptance of mindfulness-as-healthcare).
Ultimately, there appears to be an intuitive consensus that there are many things that we should consider as “healthcare” outside of what happens in a doctor’s office. Validation via rigorous research studies will be a critical bridge for companies that want to position their products in that growing category.
Back in CAC
Another advantage of creating research-based validation of the outcomes of a product would be to establish a durable customer acquisition tool.
CAC inflation is rampant across industries - just this week Teladoc ($TDOC) reported that they were experiencing lower productivity from their advertising spend (if only someone saw this coming). It turns out that if you advertise on over 600 different podcasts (2x the spend of the next closest advertiser) you might hit a cliff of diminishing returns.
The ROI on conventional ad spend categories may languish further as privacy changes hamstring ad targeting.
Creating data-driven validation of outcomes via an RCT might emerge as a compelling, durable signal to prospective customers. A real-world example comes from an e-mail ad I got coincidentally this week from Therabody touting results of a clinical trial for its new TheraFace product:
I would expect that this type of marketing would have strong, but probably not broad appeal - not everyone cares how “legit” something (see: the ~$100bn supplement market lol), but clinical validation will go a long way in building trust with consumers who do care about it. Nonetheless, it offers another tool in the arsenal for companies seeking to differentiate from the competition.
Not so fast
Despite my optimism, there are meaningful barriers to adoption of strategic clinical research. A lot of prospective research sponsors might be worried that the research they conduct wouldn’t yield the desired outcome - i.e. what if you run a study that shows your product doesn’t work! Another concern is new entrants pushing the boundaries of ethical study design and execution. New York Magazine’s Cover Story podcast had an excellent series on the shady practices in certain corners of the psychedelic medicine industry. Integrating with standard IRB and ethics review processes will be critical as new entrants aim to safely navigate the complexities of research.
Ultimately, the democratization of clinical research, particularly on the less-capital intensive periphery of the industry, is positioned to meaningfully accelerate scientific progress. I, for one, look forward to the day that we can all participate in a Liver King sponsored clinical trial to study the health benefits of the simulated-hunt-all-raw-meat diet (atkins walked so liver king could run 😪).