I was shocked when I saw this statistic…
According to U.S. Government Accountability Office (GAO), only 5% of rare diseases have treatments approved by the FDA. Now, consider this: there are an estimated 10,000 rare diseases identified so far… and ONLY 5% have an approved treatments by the FDA. That’s impressive.
Of course, running a rare disease trial is far more challenging (both operationally and statistically) than a trial for more common diseases. Rare disease trials don’t usually follow the standard trial designs, randomization methods, or the same regulatory strategies used in broader patient populations.
As a result, rare disease trials are often associated with:
- Delays
- Protocol amendments
- Higher costs
- Trial failure
Here, I’m sharing two major challenges rare disease trials face, and the strategies we use at IDDI to minimize them.
Tip: Save this blog now so you can revisit our insights later!
Challenge #1 – Insufficient Patient Accrual
A study analyzing 199 discontinued rare disease trials found that 33% failed due to insufficient patient accrual (PLoS Med. 2019 Nov. e1002966). That’s a huge problem.
One major reason? Rare disease patients aren’t concentrated in a few hospitals (or even a few states or countries). Instead, they are often spread across multiple regions, making recruitment a significant challenge.
Why this matters:
Without a strong recruitment strategy, it becomes difficult to enroll enough patients to ensure credible statistical results.
It’s known that recruitment delays lead to:
- Longer trial timelines, increasing costs.
- Protocol amendments, requiring additional approvals.
How to avoid this challenge:
Challenge #2 – Should a Rare Disease Trial Use Randomization?
Okay… This is more of a question than a challenge, but in reality, it is a challenge, and the answer is crucial for any trial.
The short answer: It depends on the trial’s context, such as the disease, ethical considerations, and feasibility (both operational and statistical).
If randomization is possible, it can be beneficial because it reduces bias. However, in many rare disease trials, randomization may not be feasible. In such cases, innovative trial designs (like those mentioned earlier) may be better alternatives.
Before the long answer, if you need to design a rare disease trial and want to avoid all the specific mistakes that will compromise your trial, reach out here to speak with our team of world-renowned strategic consultants.
That said, we know that randomization (and stratification) minimize bias by balancing treatment groups. This results in statistically stronger and more reliable results and conclusions. Fantastic!
But what if the disease only affects 30 or 40 patients worldwide? Or what if there are more patients, but logistical constraints (trial site availability and geographic spread, for example) prevent broad participation? Then, randomization could be problematic. Splitting an already small group into separate treatment arms could make detecting meaningful treatment effects difficult.
Now, if the trial can recruit hundreds of patients, randomization might make sense, but careful planning is required to be sure that prognostic factors are balanced. Stratification is often necessary to equally distribute key subgroups (e.g., different disease severities) across treatment arms.
As I mentioned, it depends on the context. We’re currently preparing a detailed blog that covers key aspects of randomization, including what to plan for and evaluate when designing a trial. More on that soon!
That said, you can overcome the challenges of rare disease trials by connecting with our team of world-renowned strategic consultants here.
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