Putting patients at the heart of clinical trials

‘Patient-centric’ trials have been a hot topic for several years, with a big emphasis on trial design. It is well known that putting patients at the heart of the clinical trials process can improve recruitment and retention rates [1], which is much needed considering that 85% of all clinical trials fail to recruit sufficient patients and 80% are delayed because of recruitment delays and high dropout rates [2]. Most recently, the COVID-19 pandemic has shone a light on the importance of diverse representation in clinical trials to make them more patient centric. The US FDA and the Pharmaceutical Research and Manufacturers of America (PhRMA) have recently issued new guidance and principles on how to enhance this [3,4].

However, it is not just the trial itself that we need to look at for the development of new interventions to be called truly patient-focused. We need to look back along the timeline to as early as setting research priorities and then as far forward as the dissemination of study results. It is not just about asking a patient how many site visits a month they would prefer, in order to “tick the patient-centric box.”

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Setting research priorities

From the outset, clinical trials are only fit for purpose if the intervention being tested is, if successful, ultimately going to fulfill patients’ needs. To determine this, it is necessary to find out what is actually important to patients. A clear example of misplaced assumption of what is important to patients is that for years the success of disease-modifying drugs in multiple sclerosis (MS) trials has largely relied on measuring impact on walking ability. However, the Barts-MS ‘#ThinkHand’ campaign clearly highlighted that people living with MS viewed hand function to be important for retaining independence, especially when leg function had already been affected by the disease [5].

Working with the patient community, regulators, charities and industry, the team has managed to put what MS patients want onto the clinical trial agenda: Roche (Basel, Switzerland) is now sponsoring an international Phase IIIB clinical trial for ocrelizumab (ORATORIO-HAND) for people with primary progressive MS that will use hand function as the primary outcome measure [6]; and ChariotMS, which will be partly funded by the MS Society (London, UK) and National MS Society (NY, USA), will test if Merck Serono’s (Darmstadt, Germany) cladribine can slow down deterioration of arm and hand function in people with advanced MS, with recruitment commencing in early 2021 [7].

Trial design

Having a clinical trial that supports good patient participation is critical to ensuring patients remain in the trial and adhere to the treatment regime. It is not enough to assume that patients will do what they are supposed to because that is what they have been told to do. Trials need to fit around the patient as much as possible. To ensure this, it is imperative that sponsors understand the lives of potential participants, what it is like to live with a disease, what challenges people might face and how they manage their daily lives. Choice is everything. Whilst decentralized trials are often held up as the ultimate solution for making trials more flexible and less burdensome, they may not be suitable for everyone.

Cultural factors may mean that for some patients it is not desirable to have a “trial come to them”, either because it means that the wider community will know that they are sick or because it is not acceptable to have a healthcare professional in their home. Limited access to technology might make it hard to monitor progress at home or communicate remotely with the trial team. Similarly, too many site visits, sites located far from someone’s home, insufficient financial and/or logistical support and burdensome drug administration regimes can all affect somebody’s experience participating in a trial. Patients can be involved in designing the trial through focus groups, interviews, dummy runs and simulations. If the effort is made to engage patients in the design from the outset, the trial will more likely suit the needs of the participants.

Diversity and cultural sensitivity

As a female of Asian origin who was born and brought up in the UK, it’s important to me to know that medications I take have been tested in people like me. Not only that, but clinical trials give people access to innovative treatments that might have the potential to change their life with a disease. This access should be available to everyone, regardless of what their heritage is, where they live or what their financial situation is.

Improving diversity in clinical trials is a complex issue. It is one where we first need to define what we mean by ‘diverse’, given the context and circumstances of each individual trial. Do we mean the trials need to be ethnically diverse? Age diverse? Socio-economically diverse? Geographically diverse?

When certain diseases are particularly common in certain groups, for example sickle cell anemia in people of African or Caribbean heritage, it would make sense to have a large representation of those groups within trials for that disease. There also needs to be better understanding about the barriers to clinical trials for underrepresented groups and, more importantly, there needs to be coordinated and tangible action from the communities themselves, regulators, industry and healthcare professionals to break down these barriers. It will mean thinking outside the box, choosing new trial sites, working to develop more diverse trial teams, creating information that is culturally, linguistically and educationally appropriate, and improving trust between communities and the healthcare industry.

Dissemination of results

Considering and involving patients does not stop when the trial ends. Ensuring they have access to understandable information about results, whether negative or positive, can support informed decision making about treatments. With the new European Clinical Trial Regulation (EU) No. 536/2014 that will mandate plain language summaries, hopefully patients will start to have greater access to such information. However, more work is still required by sponsors to commit to producing these summaries and making them more widely available in the public domain because such summaries are currently scarce [8]. They also need to be developed with patients as standard, not as an ‘innovation’, and this type of information needs to be open access, not hiding behind a paywall. Plus, it should be made available in local languages. Access to such information should not be reserved for people who speak English. There has already been some work on involving patients in congresses and conferences too, where trial results are discussed and debated. With COVID-19 taking many of these events virtual, organizers need to continue to afford patients access to these important channels for learning about new developments in their particular disease area. If patients can have access to the same information that their doctors do, it will enrich conversations in clinic and could encourage greater shared decision making.

We need to stop thinking about patients as passive subjects in clinical trials and more as active participants in the process. They can provide key insights and advice on how to successfully develop the medicines that will directly impact them. Their involvement is no longer “nice to have” but should be an embedded and essential part of the medicines development lifecycle.

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Disclaimer
The opinions expressed in this editorial are those of the author and do not necessarily reflect the views of Neuro Central or Future Science Group.

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