When clinical development goes wrong, RWE provides solutions

In the world of biotech, even the most meticulously constructed clinical development plan (CDP) can go sideways. We all know the adage about best-laid plans. In drug development, it’s practically a daily mantra. Recruitment stalls, interim results throw a curveball, a competitor suddenly shifts the goalposts, or regulators send you back to the drawing board. For a small biotech, these aren't just hiccups; they can feel like existential threats, dialling up the pressure to adapt or face a grim reality.

But here’s the thing: when your CDP veers off course, burying your head in the sand or blindly pushing forward isn't a strategy. You need objective insights to understand what’s happening and how to navigate the storm. This is where real-world evidence data gleaned from electronic health records, claims databases, patient registries, and the like  transforms from a background concept into a critical toolkit for diagnosis, re-evaluation, and strategic redirection.

The "Oh Sh!t" Moment: Recognising Your CDP is Off Track

Let's be honest, every drug developer has been there, that sinking feeling when:

• Recruitment is a nightmare: Weeks turn into months, and patients meeting your precise criteria are rarer than a straightforward regulatory pathway. You’re burning cash, and the timeline is slipping.
  
  
• Interim results are… surprising: Perhaps the primary endpoint looks wobbly, but there's an intriguing signal in a patient subgroup you hadn't prioritised. Or worse, the results are simply inconclusive.
  
  
• The landscape shifts: A competitor publishes stellar data, or a new standard of care emerges, suddenly making your drug’s proposed positioning look less compelling.
  
  
• Regulators raise new questions: Feedback from health authorities necessitates a significant rethink of your trial design, endpoints, or even the target population.

In these moments, clear thinking is paramount. Panic is a poor counsellor. Objective data, however, can illuminate the path forward. RWE offers that crucial, unbiased lens.

RWE to the Rescue: Practical Ways to Course-Correct

When your CDP hits the skids, RWE can help you figure out what went wrong and, more importantly, what to do next.

1. Diagnosing the Problem: Why Did We Stumble?
   
   Before you can devise Plan B (or C, or D), you need a clear-eyed understanding of why Plan A faltered. RWE provides the diagnostic tools.

• Untangling Recruitment Knots: If patients aren't enrolling, RWE can help you understand why. Are your inclusion/exclusion criteria too restrictive for the real-world patient population? Are you looking for patients in the wrong places? RWE can analyse actual patient distribution, compare their characteristics against your protocol, and map out genuine care pathways. Perhaps the "ideal" patient defined in your protocol is incredibly difficult to find, or they are being managed in settings you hadn't considered. RWE can expose these misalignments.
  
  
• Making Sense of Ambiguous Trial Data: If your trial results are murky – maybe you missed the primary endpoint but saw an interesting effect in a specific subgroup – RWE can add vital context. Is this subgroup identifiable and substantial in routine clinical practice? What are their current treatment options and outcomes? RWE can help you assess whether pursuing this subgroup is a viable pivot or a statistical ghost. It can also help understand if unexpected variability in your trial results might be explained by real-world patient heterogeneity not fully captured by your initial assumptions.

2. Finding a New Path: Pivoting with IntelligenceOnce you have a better grasp of the problem, RWE can help you identify and validate alternative strategies.

• Uncovering Niche Opportunities or Orphan Indications: Your drug might have genuine potential, just not in the broad population you first targeted. RWE can be instrumental in identifying well-defined, underserved niche populations or even exploring orphan indications. By analysing prevalence data, current treatment gaps, and the real-world burden of illness in specific segments, you might uncover a more focused, and potentially faster, path to market where your drug’s benefit-risk profile is more compelling.
  
  
• Repositioning or Exploring Combination Therapies: The treatment landscape is dynamic. RWE can help you understand how your drug might fit into evolving paradigms. Are there emerging rationales for using your therapeutic in combination with other agents? RWE can analyse real-world data on concomitant medication use, treatment sequences, and associated outcomes to identify potential synergies or patient groups who might benefit most from a combination approach. This can breathe new life into a programme.
  
  
• Contextualising Single Arm Data with External Controls: This is a more nuanced application and comes with significant caveats, particularly regarding regulatory acceptance for primary evidence. However, if a single-arm study has produced intriguing data but lacks a direct comparator, RWE can sometimes be used to construct a retrospective external control arm. This involves identifying a comparable group of patients from real-world data sources to provide context for your findings. While unlikely to replace a well-designed randomised trial for definitive proof, it can be invaluable for internal decision-making, hypothesis generation for future studies, or supporting early discussions about a revised development strategy.

3. Reinforcing Plan B: Building a Solid Case for the New DirectionIdentifying a potential new direction is one thing; convincing stakeholders (investors, partners, regulators, your own team) that it’s the right move is another. RWE is vital for building this new case.

• Quantifying the Revised Opportunity: If you pivot to a new indication or a more defined patient subgroup, RWE helps you accurately estimate the size of this new target market and substantiate the unmet medical need. This isn’t just about numbers; it’s about demonstrating a clear understanding of who these patients are and why your drug matters to them.
  
  
• Assessing the Feasibility of New Trial Designs: Any new clinical path will likely require new trials. RWE can, once again, help assess the feasibility of recruiting for a revised protocol in your new target population, stress-testing your assumptions before you commit significant resources.
  
  
• Strengthening Stakeholder Dialogue: When you’ve hit a setback, transparency and a data-driven recovery plan are key. Using RWE to demonstrate that you’ve rigorously analysed the situation, identified a viable and evidence-backed path forward, and truly understand the new context for your drug is critical for rebuilding confidence and maintaining momentum.

The Mindset Shift: RWE for Continuous Learning and Adaptation

Perhaps the most important shift is to stop seeing your CDP as a static document, etched in stone. Drug development is an iterative learning process. RWE shouldn't just be a rescue tool deployed in a crisis; it should be an integral part of your ongoing surveillance and strategic thinking. Proactively using RWE to monitor the evolving competitive landscape, shifts in standard of care, and emerging patient needs can help you anticipate potential challenges and adapt your plan before you hit a major roadblock.

When the Plan Changes, Let Data Guide You

Setbacks in clinical development are, unfortunately, part of the territory. How you respond to them defines your biotech’s resilience. Instead of relying on hope or guesswork, RWE provides the robust data and actionable insights needed to critically re-evaluate your position, re-strategise intelligently, and potentially rescue a programme that’s gone astray. For small biotechs navigating the perilous journey of drug development, the ability to adapt and pivot based on sound evidence isn't just an advantage, it’s a lifeline.