In short

  1. On-time enrollment is crucial for the success of a clinical trial to:
    1. Beat the competition to market
    2. Ensure there are no unnecessary financial implications to the trial
    3. Fulfil the ethical promise to patients enrolled in the trial
  2. A large biopharma sponsor needed support with two phase 3 studies as part of their program in patients with MS
  3. Using evidence-based feasibility studies, PSI projected a recruitment rate that would far exceed the industry standard. Enrollment completed over 2 months ahead of schedule
  4. Following changes to the study drug formulation and trial protocol, PSI kept sites motivated and informed about the progress throughout the startup delay
  5. Investigators received individual support to rescreen patients who were initially ineligible due to the protocol-mandated washout period. As a result, most were able to enter the trial
  6. With successful enrollment and subsequent approvals by the FDA and EMA, PSI continues to partner with the sponsor on two additional trials using a different formulation

Why does on-time enrollment matter so much in neuroscience?

  • Beating the competition to market: On-time enrollment is required in competitive fields to ensure that the best drugs reach the market first, ahead of potentially less efficacious or safe treatments
  • Financial implications: Delays in enrollment cost money. Delays in getting to market cost money. Recent data estimate one day of delay to cost up to $500,000 in lost drug sales, and $40,000 in direct daily clinical trial costs [1]. Slow enrollment is financially impractical and unworkable
  • Ethical responsibility to patients: If enrollment doesn’t proceed on time, or the trial cannot be completed due to low enrollment, the time and the risks that patients who were enrolled took will not have been worthwhile

Enrollment in neurological trials can be tough. In trials in other therapeutic areas, eligibility criteria may screen out for cognitive dysfunction [3], which is often a key symptom (or target) in many neurology-focused trials (including for MS [3]). Understanding and providing support to patients to help them overcome their challenges and attend appointments, in addition to attending to caregiver needs, ethical considerations, and burdensome procedures, can make neurological trials among the most difficult to recruit for.

The challenge

PSI helped a biopharma sponsor complete two phase 3 trials in MS on time, even after the enrollment targets were revised to increase sample size by approximately 50%. Based on data from this program, the FDA and EMA approved the sponsor’s drug for the treatment of patients with MS.

What were the keys to success?

The solutions

Realistic, evidence-based enrollment targets

The sponsor planned to enroll between 500 and 800 patients in each study. PSI developed an enrollment scenario based on real-world evidence and our experience. When the sponsor requested additional sites as our projected recruitment rate was higher than the industry average, we included them and still enrolled at our initial rate, completing enrollment almost two months ahead of the sponsor’s goal. PSI’s overall enrollment rate in MS is 52% higher than the industry average.

Individualized site support

Is there such a thing as unique site support? PSI’s MS site network comprises 900 sites across 30 countries, all of which are regularly inspected by the FDA and EMA. Each of these sites is different, and recruiting patients at each site presents its own challenges.

Changes to the study drug formulation and protocol were made during the EU submissions and SSV processes, which raised questions from regulatory authorities, delaying site startup. Despite these challenges, PSI motivated sites and kept them informed of developments. Nearly all selected sites for these two trials recruited at least one patient; less than 10% of sites did not enroll any patients, which is far below the industry average.

Understanding the trial protocol

PSI’s experienced, global MS team thrives on working with sponsors to achieve their goals. In these trials, many patients were initially screened out due to protocol-specific exclusion criteria. The PSI team collaborated with investigators to rescreen prospective patients some months later, and most were able to enter the study.

PSI’s MS therapeutic area lead has over 20 years of experience at PSI. Along with the global group of MS project leaders and PSI’s Scientific Advisory Board of world-leading KOLs, the expertise that can be drawn upon is immense. The sponsor and PSI worked together on key decisions throughout the trial process, including protocol feedback and support, to ensure the trials ran on time according to the protocol. Over the past five years, 75% of MS drug approvals have been based on data generated with the support of PSI.

The outcome

Based on these successes, the sponsor chose PSI to run their successive trial. Furthermore, the sponsor recently awarded PSI yet another trial based on the strength of PSI’s neurology experience and the sponsor’s fond memories of on-time enrollment and delivery in prior trials.

Thank you to the entire PSI team for all your efforts for the duration of our relationship. We were certainly faced with some interesting challenges, and we really appreciate the willingness to be collaborative and come up with helpful solutions. [The sponsor’s] management appreciates all the hard work.

Chief Financial Officer, Sponsor

Key takeaways

Partnering with a CRO that takes enrollment seriously, considers all options for site-specific support, and delivers (or overdelivers) on its initial projections often results in expedited timelines for approval of the sponsor’s drug. Working with the same proactive and experienced CRO over several years builds trust and a deeper understanding of each other’s ways of working. Choosing the right CRO and maintaining a strong relationship are critical factors in achieving success.

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Abbreviations

CRO, Contract Research Organization;
EMA, European Medicines Agency;
EU, European Union;
FDA, Food and Drug Administration;
KOL, Key Opinion Leader;
MS, Multiple Sclerosis;
SSV, site selection visit.

References

1. Getz, K., How much does a day of delay in a clinical trial really cost?, in Applied Clinical Trials. 2024.
2. Newberry, A., et al., Understanding recruitment and retention in neurological research. J Neurosci Nurs, 2010. 42(1): p. 47–57.
3. Benedict, R.H.B., et al., Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. Lancet Neurol, 2020. 19(10): p. 860–871.