Trial Budgeting and the Protocol

This topic is designed for start-ups operating with limited resources—not for those fully financed and capable of addressing multiple trial goals simultaneously. When resources are tight, prioritization is essential. Specifically, you must focus on achieving goals that will advance your company to the next round of financing or secure a partnership with a larger organization. Using a Phase IIa clinical proof-of-concept (POC) trial as an example, we will outline how budgeting aligns with these goals.

Key Objectives for a Phase IIa POC Trial:

1. Statistically Significant and Clinically Relevant Results: Demonstrate improvement in the treated cohort versus placebo that is both statistically significant and meaningful for the indication.

2. Validated Endpoints: Use endpoints that are well-validated, commonly accepted by the FDA and industry, and applicable to future pivotal trials.

3. Straightforward Trial Design: Keep the efficacy design classical, simple, and easy to communicate. Avoid overly sophisticated designs that require extensive explanation.

4. Rigorous Methodology: The trial should be double-blinded, placebo-controlled, and randomized (e.g., 1:2 ratio).

5. Robust Statistical Power: Ensure the trial is powered for well-accepted endpoint significance (targeting p < 0.05). Moreover, the clinical relevance of efficacy improvement must be evident. For instance, while a 5-meter improvement in 7-minute walking distance for claudication patients may be statistically significant, it is not clinically meaningful.

By aligning the trial design with these goals and budget constraints, it is possible to execute a POC trial effectively within limited means.

Phase Bridge's Approach to Trial Budgeting

We specialize in designing and executing clinical trials that address immediate company goals while working within constrained budgets. Below are the steps we typically take when collaborating with clients:

1. Determine Available Resources:

   1. Assess how much the company can allocate to a POC trial while accounting for internal burn rates during the anticipated trial period.

   2. If necessary, recommend drastic cost-saving measures, such as reducing internal staff and outsourcing operations, to preserve resources.

   3. Example: If the company has $2M in the bank, with $0.5M required to sustain operations until the trial's conclusion, $1.5M can be allocated to the POC trial.

2. Establish a Dedicated Trial Budget Account and Segregate resources:

   1. Open a separate checking account and deposit the allocated funds. Restrict withdrawals to direct clinical trial costs to ensure disciplined spending.

3. Eliminate Unnecessary Endpoints:

   1. Focus only on essential, well-accepted endpoints to reduce costs.

   2. Examples:

      1. Strip MRI: Not a primary or well-accepted endpoint for heart failure.

      2. Remove Smartwatch Readings: While appealing on paper, they may lack regulatory acceptance (e.g., for hot flashes).

4. Estimate Per-Patient Costs:

   1. Determine costs based on endpoint requirements. For example, if the per-patient cost is $8K, including CRO services, this could increase to $15K per patient. A $1.5M budget can accommodate 100 patients.

5. Partner with a Single Clinical Site:

   1. Collaborate with a large medical center that can conduct the trial within the allocated budget. Negotiate for the site to use its own CRO and medical monitor, maximizing efficiency and minimizing overhead.

   2. Major medical centers often have internal CROs capable of handling external projects, creating cost-saving opportunities.

6. Optimize Enrollment Criteria and Power Calculations:

   1. Work with the site’s Principal Investigator (PI) and Key Opinion Leaders (KOLs) to finalize enrollment criteria and ensure the trial is adequately powered for the targeted endpoints.

Considerations for Investigator-Initiated Trials

While investigator-initiated trials (IITs) may seem attractive due to fixed costs and reduced financial risks, they have significant downsides:

• Dependence on a single trial site, which can lead to delays if the site struggles with enrollment.

• Higher costs as centers often charge more for IITs to cover additional FDA-related responsibilities.

Simplifying FDA Interactions

For Phase II trials focused on safety and secondary efficacy, FDA interactions are typically straightforward. A fully developed protocol from the trial center and an IND package prepared by a regulatory consultant (costing ~$50-80K) are usually sufficient. If all FDA requirements are met, even non-regulatory specialists can manage correspondence effectively.

Key Takeaways

Prioritizing endpoints, refining patient sub-populations, and understanding how to ease the clinical trial site's workload can result in a budget-friendly yet impactful trial. By leveraging strategic trial design and cost-effective solutions, you can achieve meaningful results that propel your company forward.