The 90/10 for biotechs: The minimum viable evidence framework

In the high-stakes, resource lean world of biotech, you’re constantly battling a tide of demands. There are a thousand scientific questions you could explore, a hundred potential evidence gaps you could try to fill, but realistically, you only have the bandwidth and budget for a select few. So, how do you choose? How do you ensure your precious resources aren’t just spent, but strategically invested?

The answer lies in a concept you might have heard of, often called the Pareto Principle, or the 80/20 rule. We’re going to call it the 90/10 rule for our purposes: the idea that a mere 10% of your evidence generation efforts will likely drive 90% of the real value for your clinical development programme. The trick, of course, is identifying that critical 10%. This isn't about luck; it's about a disciplined, strategic approach.

Why Most Evidence Generation Yields Only Incremental Value (And Why You Can't Afford That)

Let’s be frank. There’s a constant temptation in science to chase "interesting" data. We’re curious by nature. But for a small biotech fighting for its next milestone, "interesting" doesn’t pay the bills or get a drug approved. Too often, efforts get diluted, generating data that’s confirmatory but not game-changing, or filling evidence gaps that aren’t directly on the critical path to your next major decision point. This kind of incrementalism, this "data for data’s sake," is a luxury you simply cannot afford. Each pound spent on evidence must be a heavy hitter.

The Framework: An Approach to Pinpointing High-Value Evidence Gaps

Step 1: Define "Value" For Whom and By When? (The Stakeholder Compass)

Before you even think about evidence gaps, you need to be crystal clear on what "value" means for your programme right now. Value is in the eye of the beholder. Are you hurtling towards a crucial End-of-Phase-II meeting with regulators? Then "value" is the evidence that directly addresses their anticipated concerns and gets you a green light for Phase III. Are you gearing up for a Series B funding round? Then "value" is the data that de-risks your proposition in the eyes of (un)savvy investors and convinces them to issue a term sheet.

Identify your primary stakeholder(s) for your next major inflection point. What are their key decision-making criteria? What are their biggest anxieties or perceived risks concerning your asset? This understanding defines your target and dictates what kind of evidence will be truly valuable, versus merely informative.

Step 2: Brainstorm Broad Challenge Areas (The "Problem Landscape")

With your definition of value and your key stakeholder in mind, step back and map out the major known hurdles, uncertainties, or challenges facing your clinical development programme. Don't get bogged down in minute details yet; think at a higher level. These could include:

• Uncertainty around the strength or durability of clinical efficacy/safety signals.
• Challenges in patient selection or dealing with patient heterogeneity.
• A lack of clear differentiation from current or emerging competitors.
• Ambiguity in the optimal regulatory pathway or specific agency requirements.
• Looming questions about market access, reimbursement potential, or pricing.
• Concerns about the feasibility of recruiting for pivotal trials in a timely manner.

Step 3: Deconstruct Challenges into Specific Evidence Questions (The "Issue Tree" Logic)

This is where you start to get granular. Take each broad challenge area you identified and break it down into a series of specific, answerable questions. If these questions were answered with robust evidence, they would significantly mitigate or resolve the overarching challenge. This process, akin to using an issue tree, helps you systematically uncover potential evidence gaps.

Let’s take an example. Say a broad challenge is: "Uncertainty about competitive differentiation for our lead asset." Specific evidence questions (and thus potential gaps) might include:

• "Do we have compelling head-to-head data, even if indirect or from RWE, against the most relevant comparators on outcomes that truly matter to clinicians and patients?"
• "Can we clearly articulate and evidence a superior benefit-risk profile in a well-defined patient subgroup that competitors don't adequately serve?"
• "What is the real-world burden of illness not addressed by current therapies that our drug can address?"

Be hypothesis-driven in your thinking: "We believe a critical evidence gap is X (e.g., lack of data on long-term patient-reported outcomes), because if we successfully address X, it will directly tackle Y concern (e.g., demonstrating sustained quality of life benefit) for Z stakeholder (e.g., payers)."

Step 4: Prioritise – Applying the 90/10 Filter (The Impact/Feasibility Crunch)

You’ll now have a longer list of specific evidence questions and potential gaps. Not all of these are part of your critical 10%. It's time to filter ruthlessly using a classic prioritisation tool: the Impact/Feasibility matrix.

For each potential evidence gap, ask two critical questions:

1. Impact: If this specific gap is filled, how significantly will it influence our primary stakeholder's decision (from Step 1) and help us achieve our immediate strategic goal? Score this High, Medium, or Low. Be honest – is it a game-changer or a minor improvement?
   
   
2. Feasibility: How quickly, cost-effectively, and realistically can we fill this gap with credible evidence? Consider if real-world evidence (RWE) could provide a faster or more efficient answer than a new prospective study, or if re-analysing existing data could suffice. Score this High (quick, affordable), Medium, or Low (long, expensive, complex).

Your "10% evidence gaps" – the ones that will drive 90% of the value – will typically reside in the High Impact / High Feasibility quadrant. These are your immediate targets. Don’t ignore High Impact / Low Feasibility gaps, though; for these, ask: "Can we break this down? Is there an interim piece of evidence we can generate that would partially de-risk this issue or provide directional insight?"

Moving from Identification to Action: What Next?

Once you’ve pinpointed your handful of high-value evidence gaps, the work isn’t over. The next step is to define the minimum viable evidence (MVE) required to address each one effectively for your current purposes. What does "good enough" look like to make that next crucial decision or satisfy that key stakeholder? It might not be perfect, peer-reviewed publication-level data initially; it might be a robust internal analysis or a targeted RWE study.

Develop a lean action plan – almost a mini-Integrated Evidence Plan (IEP) – for these critical few gaps:

• What specific data is needed (RWE, clinical trial sub-analysis, literature review, etc.)?
• What methods will be employed?
• Who on your team (or which external partner) will own this?
• What is the realistic timeline?

And remember, this isn’t a one-and-done exercise. As you generate new evidence, as the competitive and regulatory landscapes shift, your "10% of gaps" might also evolve. Revisit this framework periodically.

The Trap of "Data for Data's Sake" (A Final Warning)

This entire framework is designed to drive strategic evidence generation, not just accumulate data. Resist the powerful allure of pursuing every scientifically intriguing question unless it directly aligns with your prioritised, high-impact evidence gaps. Your resources are too precious.

“Work Smarter, Not Just Harder”

For small biotechs, navigating the treacherous waters of clinical development demands more than just scientific brilliance; it demands acute strategic focus. By rigorously applying a framework to identify and then relentlessly pursue that 10% of evidence gaps that will drive 90% of the value for your current challenges, you make your limited resources punch far above their weight. It’s about ensuring that every piece of evidence you generate is a strategic asset, propelling you efficiently towards your next critical milestone and, ultimately, towards helping patients.