In the absence of support from governments, pharma and insurers, Kasey went on a one-woman survival mission that would also provide hope for other people like herself. She described her disappointment in the system and how, even in this “golden age” of cancer treatments, research in such rare diseases was non-existent, because money talks and pharma, payers and investors are only putting out where they see a return. She called out the unilateral engagement between patients and other stakeholders – where patients are used as a means to an end, not truly involved as a research partner. A few months later, the news came that Kasey had passed away and, although I never met Kasey or knew of her before her panel appearance, this particularly saddened and shamed me.

Coming from a pharma background, I know that "Patient centricity" are hot buzz words. Each company has some sort of vision statement, slogan or strapline claiming to put patients at the heart of everything they do and promising to engage patients throughout the lifespan of their medicines. Those in the industry take pride in being altruistic – claiming to bring hope to patients or putting smiles on faces. Kasey’s story says otherwise and speaks volumes in its deafening silence. And that silence is ultimately self-defeating, not just because it exposes blatant hypocrisy in the life sciences industry’s stated aspirations and values, but as a missed opportunity to gain rich input from fundamental stakeholders such as patients and patient organizations to make sure their actual needs are met. Engaging with these people, without whom there would be no industry to work in at all, would raise all tides no matter the complexities and challenges while also meeting the value standard the industry claims to champion.

The insights afforded by people living with disease and their carers can provide a different (and potentially better) direction into a company’s activities over and above those which can be gained from making assumptions that "the doctor knows best" through traditional physician insight gathering, such as advisory boards, consultancy, etc. However, to Kasey’s point, we need to ensure that such patient/public involvement is wide-ranging, has mutual benefit and is not done as a public relations "tick-box exercise" or be simply for company gain when the business case is positive.

It is increasingly recommended and required that there is patient and public involvement in the design, conduct, and dissemination of health and social care research. Indeed, many journals now require details of how patients have been involved in the development of a research project to be clearly articulated in primary manuscripts (and details of, if not, why not? mentioned). As well as ensuring clinical research is relevant and conducted appropriately, deep insights from patient engagement can help inform medical education and communication activities aimed at HCPs.

However, while there are clearly many benefits for pharma, if patients are to be asked to provide their time, thoughts and insights, there must be mutual benefit for both parties involved. For any patient engagement activity, we challenge a company to ask itself what positive impact this initiative will have for the patient community. Without a win-win scenario in play, patients need to speak up and confront companies to make sure their involvement will directly promote their care and future, not just help satisfy a business plan.

Patients are reliant for the most part on academic and industrial researchers to represent their cause when it comes to furthering knowledge and study of their diseases to bring new treatments to the fore. The lack of effort put into diseases that are too rare to build a business case for investment or too difficult to study must devastate people living with progressive and/or deadly diseases as they see time ticking by with no activity to support them. Patients and carers should not have to take the sort of steps that Kasey and her family did to try to find a solution (ploughing literature, finding experts, raising research funding single-handedly), nor are many of them capable of this. There needs to be a change in mindset in terms of patient engagement so that it is not based on “building a business case” but instead supporting the people that matter.

In terms of research, the cornerstone of an innovation-led industry such as pharma, the lack of useful studies is disappointing (1). Clinical research by nature involves people as participants, puts them through intensive and invasive protocols as experimental subjects, and fosters (but also potentially dashes) their hope for a cure or improvement. Therefore, clinical studies must be useful, and not just built for business—they need to make active steps forward to making a difference for patient health and disease outcomes or at least should be undertaken with that as a realistic prospect.

A recent review of why most clinical research is not useful highlighted the lack of patient centricity as a key concern. When designing or conducting clinical studies, researchers need to question whether the topic under consideration is a priority for patients – do they really care about this issue, would they support the cause? Patient engagement in even well-researched therapy areas is key to truly understand the real unmet needs or patient concerns for their disease. Even for an Nth to market therapy, having a better insight into what patients are bothered about could help drive an innovative trial design, differentiating set of meaningful endpoints or help set up a pathway to alternative funding models.

Particularly in rare diseases, where the patient voice may be diminished or even silent and external knowledge is limited, it is more important than ever to involve patients/carers in the design of studies aiming to bring new medicines into their care pathway. As an example, when considering a study into a very rare, very complex, metabolic disease, patient engagement was key to defining some of the patient reported outcomes that would underpin the efficacy of the treatment (2). These insights would help inform clinically relevant outcomes that would not only satisfy regulators and payers, but also actually be meaningful to the patients themselves.

This exercise used two different means of patient engagement – the first through one-on-one qualitative interviews with adult patients as well as parents of children living with this disease. The second approach, in pandemic times, used a Zoom call facilitated discussion focus group, with several patients and carers on the call together. Both initiatives provided rich information to help guide protocol design (practical and logistic issues were candidly discussed) as well as give clues into the key features of the disease that were important to patients and parents. Results were remarkably similar despite the different methodologies and different countries in which the engagement took place.

The most humbling, and rather poignant observation was, however, just how surprised and grateful the people were for actually being asked their opinion. They remarked on the lack of research or even attention to their disease and were amazed that anyone was doing anything, let alone anyone being bothered to consult them. This is a sad situation and a wakeup call for all of us to realise how people living with disease can feel so neglected and alone.

While ethical review and approval of a clinical study is mandatory for researchers, regulators, and ethics committees, the patient perspective also needs to be considered. The balance of benefit and risk in a clinical trial is frequently judged differently by clinical or ethical stakeholders compared with patients due to their different focus (3). For this reason, even before we have got to trial design or submission for ethics approval, it is crucial to involve patients in dialogue as to what is acceptable to them in terms of intervention and risk. It is quite possible that, either one way or the other, patients may or may not be willing to undergo protocol-driven activities were considered either unacceptable or perfectly fine by the study designers. Direct patient engagement is key.

As an example, a study in infants (<1 year) with an extremely rare disease was mandated by the regulatory authorities as part of the approval for a new medicine (4). It was clear that recruitment would be a challenge as it was going to be very difficult to find expectant mothers or infants very soon after birth (a microscopic needle in a very big haystack!). However, once found, it was imperative to ensure participants would be motivated to take part and complete the study (parental and participant burden would be a challenge at this delicate and vulnerable stage in life). The clinical team consulted with investigators as part of a typical study protocol advisory board, who provided their insights and guidance on what they thought would and would not be acceptable for parents and their babies.

It is fortunate that the team did not stop there. As well as physicians, the team consulted with patient advocacy groups and also parents of children with this disease – and the results were astounding. Opinions between the healthcare professions and the patient groups and parents were often divergent, to the point where following the lead from the physicians would have been detrimental to recruitment and completion of the study. There were many insights only uncovered from talking to the parents (even over and above the advocacy groups) that informed the protocol design, acceptable interventions and endpoints gathered. The protocol was adapted accordingly and went on to be successfully implemented. In particular, the patient advocacy group, having been involved from the start, was super helpful in finding potential parents and subjects, and all parents and infants continued with the study, with no discontinuations. This was a great example of how patient involvement, engagement and insight helped to change a mandatory regulatory-driven trial into something meaningful in which the parents and patient groups saw themselves as having real influence and partnership.

Patients and their families can, and should, be engaged at all stages in the life cycle of any new medicine (5). Pre-study, patient input into protocol design, endpoint, and comparator selection as well as consideration of disease-adapted study conditions will be key. During a study, patient insights and involvement can be gained through the selection and collection of relevant patient reported outcomes, as well as gaining rich information to complement traditional endpoints through qualitative interviews and mixed methods research. After a study has completed, results can be brought to life and communicated widely through patient narratives, lay summaries and meaningfulness assessments. However, no matter when or how a company or research body decides to engage patients in their activities – the crucial question to answer is WHY.

If that WHY is because it makes sense for pharma to get a quicker/easier/better result so that they can get a quicker/bigger/better return on their investment, then I suggest we reconsider. The WHY has to be centred around what it means for the patient and what should be their motivation and ultimate benefit in contributing to the cause. If a company cannot do this, then they should think twice about calling themselves “patient centric”. Patient centricity is not just using patient insights for gain or feeling good – it has to go both ways.

Pharma should think about that if they want to engage patients—how can they do this by building real relationships and partnerships, rather than simply conducting transactional exercises for their own gain? Consideration should be given to support therapy areas or diseases that are maybe not high in business plan priorities. A little like medical teams work with academic investigators to sponsor research into more obscure uses of a medicine, so a company should contemplate how to work with patients to support them in therapy areas maybe not yet in scope or too small to make a difference to the bottom line. Rather than taking a self-congratulatory approach to patient engagement, pharma should question the reason for their activities – can it really pass a red face test of give and take? Should pharma fail in this self-reflection and challenge, and in the absence of true patient centricity, my request to patient and patient groups is to stand up strongly to ensure that their involvement is underpinned by a mutual benefit for both parties. Patients hold a powerful lever in this equation – owning true insights into a disease and treatment that only they can provide.

Kasey was a wonderful, brave and very motivated young woman. Her legacy as an empowered patient and activist lives on and should humble us all. Her call to action to not accept the unilateral engagement of patients currently in play and to demand effort even in rare conditions where investment is poor sends a strong and direct message to us all. I hope that her words will carry weight to make us reconsider how and why we engage with patients as we seek to support those who we should care the most about of all.

References

1. Ioannidis (2016) PLoS Med 13(6): e100204

2. Wood (2021) 28th Annual Conference of the International Society for Quality of Life Research. Qual Life Res 30, p.115; Poster 3062

3. Klingmann et al. (2018). Front. Med. 5: 251

4. Padidela R, et al. Hormone Research in Paediatrics. 2021;94:226.

5. Harrington et al. (2020). Value Health 23(6): 677-688