Rare Disease Clinical Research: Strategies for Ensuring Endpoint Integrity

Rare disease clinical trials can be particularly challenging when it comes to endpoints. Not only are there typically a limited number of patients that can be included in the trial, but often the endpoints themselves are novel or complex. Collaboration between subject matter experts on the teams at Medpace and ATOM International has resulted in better training and improved data visualization, pattern detection, and problem solving in rare disease clinical trials.

Medpace has collaborated with ATOM  International in order to optimize clinical trials for rare diseases, as well as clearly define trial endpoints. ATOM International works predominantly with patients experiencing neuromuscular disorders, including Duchenne muscular dystrophy, Becker muscular dystrophy, spinal muscular atrophy, limb girdle muscular dystrophy, fascioscapulohumeral muscular dystrophy and myotonic dystrophy. They also work across glycogen storage disorders such as Pompe disease and Farber disease, as well as the mitochondrial disease thymidine kinase 2 deficiency, which is an emerging treatment group. Studies of achondroplasia and skeletal dysplasia have also been included in these clinical trials.

To learn more about Medpace’s advances in the rare disease clinical trial landscape, watch this free webinar.

Clinical Trial Endpoint Development and Quality Control in Data Collection

The first clinical trial in neuromuscular disease began in 2007. “Now the field has expanded exponentially to the point where we have over 40 trials in this area,” says Meredith James, the master physiotherapist at ATOM International. “At that time, the disease-specific endpoints or outcome measures were not available,” explains James, “and we were just running with what we had.” Over the past 13 years, James and her team have developed a package of standardized training and manuals on how to collect endpoint data. They now have clearly defined disease-specific endpoints, as well as a wealth of training materials.

Since they are involved in their trials from the outset, they are able to provide advice on endpoint selection. ATOM provides consultation on protocol development, target population inclusion and exclusion criteria, endpoint information, guidance on endpoint selection and development of a clinical manual of operations in order to standardize the collection of data throughout the different clinical trial sites. Since most of their studies are global, training all clinical evaluators who will be collecting data on primary and secondary endpoints is extremely important. The ATOM team relies on Medpace’s data management team to jointly develop their source documentation.

Quality control is essential to rare disease clinical trials. A good outcome measure is reliable, repeatable, and standardized. It is also sensitive enough to measure change over the period that the trial is set. Medpace has developed standardized training procedures and manuals of operation to ensure that the variation in the data is minimized, and that the changes detected are true changes.

Medpace has also developed a standardized electronic case report form (eCRF) library for disease-specific endpoints, which is crucial to the success of rare disease clinical trials, as it facilitates the data collection and presentation at review meetings.

Planning a Rare Disease Study

Medpace’sdata management team has been working with the ATOM International group in their clinical trials for approximately six years. They began reviewing the data periodically to detect any signals in the data that could indicate issues with how the tests were being administered by the clinical evaluators at the trial sites. They have quarterly data review meetings where they provide subject profiles including demographics, adverse events, concomitant medications and any other factors that may affect the clinical evaluator tests, as well as data visualizations, so that errors can be detected as quickly as possible.

“One of the most important hallmarks of success when executing complex endpoints is to build systems with your plan in mind,” says Michelle Peterson, the senior director of clinical trial management at Medpace. Endpoint integrity is enhanced when patients are completing procedures in a specific order so that impact from fatigue and other factors are properly controlled for. Early protocol collaboration ensures that the best endpoints are selected and that they are reasonable to operationalize. For example, by strategically placing important endpoints earlier in the day, the patient’s abilities can be accurately captured. Medpace also found that optimized communication can accelerate study start-up.

Medpace has created a rare disease certificate program from a cross-functional team so that all team members working on rare disease studies benefit from their institutional knowledge and innovation. The CRAs are also highly trained to build positive relationships with trial sites in order to encourage open, honest and timely communication. They understand the amount of time and effort it takes to onboard a new team member, so they work to give the operations team as much advance notice as possible when there are changes to site staff.

Effective CE Training for Global Clinical Trials

A global reach is often necessary to obtain the required sample size for a clinical trial involving a rare disease, and Medpace works to ensure the site staff who perform the procedures are properly prepared. They have worked to finalize training manuals early in the process in order to allow adequate time for language translations and to ensure that translators are available for investigator meetings or on-site training.

Medpace continues to work towards this continuous improvement cycle to deliver the best trials possible for their patients and research partners.  To learn more about Medpace’s advances in the rare disease clinical trial landscape, watch this free webinar.

This article was created in collaboration with the sponsoring company and the Xtalks editorial team.