Roundtable summary: Decentralized trials and the collection of routine practice data for the drug benefit assessment
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Aparito and admedicum co-organised a roundtable with ten participants from the sector to discuss how decentralised trials can effectively collect data.
Dr. Andreas Reimann of admedicum set the scene with a short presentation about how admedicum works with industry and patient groups to structure data collection. There is a trend in increased applications for accelerated approval pathways for novel and innovative treatment options due to their higher efficacy in smaller patient groups.
This trend highlights the need to address the evidence gaps existing when approved products have an immature data-set and only allow for limited options to assess the products' long-term clinical patient-relevant effectiveness.
HTA bodies increasingly demand routine practice data collection to close those evidence gaps and support the drug benefit assessment. Decentralized trials offer an opportunity to collect routine practice data after product launch in order to close those evidence gaps.
The responsibility for evidence gathering should be shared with the patients and patient organisations. Critical aspects to consider here include: involving patients as early as possible, ensuring the buy-in and acceptance of patients, measuring truly patient-relevant endpoints, and designing the trial so that it’s meaningful to patients. Potential sources of routine practice data include registries, insurance or public health data, electronic patient data, healthcare apps, and wearables.
When developing a clinical trial protocol, companies need to focus on what is meaningful to patients and then co-design the trial according to that. Involving patients in clinical development demands a structured approach and is one major focus areas of admedicum.
Cécile Ollivier of Aparito continued to highlight the evidence gaps experienced by the rare disease community and Aparito’s approach to addressing those gaps. The European Medicines Agency (EMA) is calling for the move from implicit to explicit data extrapolation.
An example of implicit extrapolation is when drugs are used off label for paediatric populations based on practical experience and available data at the site level. However, this data can not be used for regulatory purposes and can serve to increase the evidence gap and competition between off label use and clinical trial enrolment.
The EMA has worked on addressing these gaps in post-marketing and reimbursement settings in the rare disease Pulmonary Arterial Hypertension (PAH). The massive off label use for most of the drugs for PAH makes it challenging to run pediatric trials and only serve to increase the evidence gap. Even after 10 years of implementation of the paediatric regulation, there are still almost no drugs licensed for children in PAH.
The following is a summary of the comments that were shared by roundtable participants. As you can see, the conversation expanded beyond decentralized trials.
Technology in decentralized trials
Routine care produces a wealth of data that can be used in the different stages of product development. Aparito recommends that when using technology to gather data, to work with patients in a way that addresses their needs and not only those of regulators and sponsors.
The use of technology in trials should be planned well ahead in clinical development, starting by collecting simple data with technology and monitoring the response from the patients. This presents an important opportunity to then make and refine the use of technology in development until progressing to the point of collecting data for endpoints.
In rare diseases, patient adherence to technology is often quite high. People living with a rare disease want to get better and are more than willing to adopt new forms of technology when reporting data. Parents of children with rare conditions can accept anything that can make life easier and be embedded in caregiving routines.
Patient reported outcomes
The EMA is highly interested in Patient-Reported Outcomes (PROs) and is moving in that direction. This may not be as explicitly communicated as in the case of the FDA due to EMA guidance publication being delayed by Brexit and the move from London to Amsterdam.
PROs are welcomed in rare diseases like PAH in children because the disease is not especially well characterised. Researchers can’t always explain how patients are responding to treatment due to a lack of established biomarkers. When you integrate innovative PROs, you should still collect data from standard PROs and have the new PROs in order to complement those and compare data over the different endpoints working with the concept of the totality of the evidence. Only a few rare diseases have validated biomarkers, which is an opportunity to work with patients to provide support on how the drug is working.
Natural history studies
Patient advocacy groups can be an especially valuable partner when generating natural history data and it’s important that they are part of the trial process. It should be developed with their advice and guidance. If you are going to include technology in your trial, make sure it meets patients’ needs. Aparito helps companies guide that process from the early stage and are experts at helping to involve patients to select the appropriate technology.
There are unfortunate examples where natural history studies funded by major pharma companies result in the data not being disclosing for other companies to also use as a reference control. Other companies or patient groups have to start over again and redo natural history studies in patient populations where they have already been carried out. This creates an additional and unnecessary burden on families and is unethical.
Lack of endpoint sinks the ship
Sometimes, companies are overly focused on drug development and are very late to discover that there is no validated endpoint for a condition resulting in an uncertain future for the compound. One of the biggest issues for any rare disease can be if the trial fails, it puts the community back 10 years and takes a long time for other companies to return and start to investigate the condition again.
Families may be very reluctant to enter a trial if there is a placebo arm. If a rescue option exists, it can make the trial much more attractive to families. By being part of a clinical trial, you are helping the next generation of kids born with that disease.
Thank you to all the participants for the stimulating conversation and we look forward to organising more roundtables in the future.