Patient and care-giver input into a Duchennes muscular dystrophy clinical trial had positive outcomes, explain Katherine Beaverson, Senior Director and Patient Advocacy Lead Rare Disease Research Unit, Pfizer and Maarten Kraaijenhagen, Senior Medical Director Rare Disease, Pfizer and PARADIGM member

Currently, there is a shift in the culture of drug development, whereby pharmaceutical companies (sponsors of clinical trials) and regulatory agencies are showing increased interest and awareness in incorporating the patient perspective.

In rare diseases, in particular, the lack of quantitative understanding of disease burden for patients and the impact of progression of disease symptoms complicates the ability to conduct effective drug development and to assess benefit-risk profiles accurately.

Increasing patient engagement and input has considerable potential to help address these matters, which could result in several important benefits, such as improved health outcomes for the patient, additional therapeutic options and a higher success rate in drug development.

At the beginning of 2019, a group of patients, patient organisations, clinicians, researchers and companies developing drugs for Duchenne came together for a workshop to discuss and evaluate the outcome measures that are currently used in clinical trials.

One of the sessions during the day involved a discussion on muscle biopsies. In Duchenne Muscular Dystrophy (DMD) trials muscle biopsies are often taken in order to obtain evidence that the compound is performing as proposed and in dose-escalating studies to discover the optimal dose for the therapeutic compound.

Biopsies can be a big concern for caregivers based on prior experience (scarring, mishandling of samples, etc.) and it is understood that young boys affected by DMD are increasingly self-conscious of resulting scarring.

The session was led by the muscle biopsy working group, which included a patient and a representative from a patient organisation, as well as clinicians and researchers. During the discussions in that session, it was felt that very little data had been collected on the patient perspective of these muscle biopsies. To address this the muscle biopsy working group decided to develop a questionnaire to allow for better insights on the view from patients and their caregivers in order for sponsors of clinical trials to improve the patient and caregiver experience when muscle biopsies are carried out in clinical trials.

In summary, the outcomes of the survey were that:

  •  Responders identified short term pain and long-term scarring as important impacts.
  • 79% of responders were little bothered about the scar and 21% were moderately or severely bothered.
  • Communication of results was considered important but received by only 26%.
  • 78% of caregivers would consider another biopsy if needed for trial participation.
  • Acceptability of biopsies in a trial depends on the inclusion of a placebo group.

The full study can be accessed here.  

Prior to this, Pfizer had met with advocates and families throughout 2017 to understand the burden of disease and the burden of clinical trial participation, inclusive of biopsies. Based on this feedback, several changes were made by Pfizer to the study protocol including a reduction in the number of biopsies required if baseline biopsies were already taken elsewhere, which is very often the case. Also, it was decided to emphasise the importance of minimising scarring at investigator meeting(s) and to add the risk of scarring in the informed consent document (ICD).

The feedback provided shaped the changes to the protocol for the phase 1b study, which had the first patient dosed in early 2018.  The above mentioned subsequent study and publication by academics and advocacy validated the patient input in a quantitative way. 

In conclusion, this case shows how Pfizer can learn from patients and advocacy when designing the phase 1 protocol and development plan of a clinical trial. The use of patient insights in the design of clinical trials, hopefully, leads to more acceptable and bearable study designs for patients and/or their caregivers.

The input acquired by Pfizer and the survey were done in parallel and were demonstrative of a multi-stakeholder effort to impact trial design.


Editorial note:

To help you plan your next patient engagement activities, PARADIGM provides a checklist as an Enhancement of the EUPATI Guidance* to help in the planning of patient engagement activities. The Recommendations on how to find the right match for the right patient engagement activity* can be used when your team is ready to reach out to patient partners, and the Patient Engagement Agreements Explained* will provide you with guidance on how to use the reference agreements and the Guiding Principles co-created by WECAN and partners.

* All PARADIGM tools will be released during the summer of 2020. Follow the information on our website. The final names of each tool might change.

This is the second article of the mini-series of six articles. Find the other articles from here.