Kate Shaw, CEO of Innovative Trials, investigates one of the biggest challenges facing clinical research today.
Personalised medicines, particularly gene and cell therapies, offer new opportunities for treating serious conditions such as muscular dystrophy, cystic fibrosis and other complex conditions like cancer and diabetes.
From the development of trastuzumab (Herceptin) for the treatment of HER2-positive breast cancer to the availability of onasemnogene abeparvovec (Zolgensma), a gene therapy that slows disease progression in children with Type 1 Spinal Muscular Atrophy (SMA), targeted therapies are contributing to improved health and longer life. It is a long way from the early days of ‘one size fits all’ chemotherapy developed in the 1940s. It is therefore no surprise that the global personalised medicine market is expected to reach almost USD 800 billion by 20281.
But just as targeted therapies offer exciting promise, so too do they highlight an urgent need to address one of clinical research’s long-standing challenges – recruiting diverse patient populations into trials. Investigating the effectiveness of these therapeutics relies on the ability of sites to recruit specific subsets of patients into Phase III trials. But without an effective patient recruitment and retention strategy to ensure the right number of eligible patients, trials risk failing before they have even started.
The challenge of diverse patient recruitment
Recruiting targeted and diverse patient populations into clinical trials has never been more important to ensure robust efficacy and safety data. This is an issue the life science sector has struggled with for years; too often, older people, women, disabled people and those from under-represented ethnic groups are missing from clinical research. This was highlighted by the Sars-Cov-2 pandemic: despite statistics consistently showing that people from Black, Asian and minority ethnic communities were disproportionately affected by the virus, fewer than one percent of the 1,518 COVID-19 trials registered on ClinicalTrials.gov by June 2020 were collecting data on ethnicity2.
The lack of diversity in research is problematic for the life science sector, but also for our global health. Between 2008 and 2013 around one in five newly approved drugs demonstrated differences in treatment response across ethnic groups leading, in some cases, to doctors prescribing drugs differently according to ethnicity3. Meanwhile, a 2020 study suggests women are nearly twice as likely as men to experience adverse reactions to therapies because drug dosages are traditionally based on clinical trials involving men4.
Reasons why certain groups have been continuously left out of research are complex: unconscious bias may play a part while research shows that cultural barriers and a lack of knowledge of clinical trials also contributes5. A lack of trust in healthcare systems, medical research and/or pharmaceutical companies can also play a part. A recent study found that more than one in three (35.5%) of participants said they did not trust pharmaceutical companies6. While no data on ethnicity was recorded, the researchers did find that women and people with poor knowledge of their condition were more likely to distrust pharmaceutical companies, which could help to explain the under-representation of certain patient groups in industry-sponsored trials.
While small steps have been taken over the years to address this, the growth of the personalised medicines market highlights a need for the industry to review its practices, become more patient-centric and commit to increasing the diversity of clinical trial participants. After all, if clinical trials for potential targeted therapeutics do not adequately represent the entire patient population in need of that specific treatment, how can we be sure it will work for everyone?
Addressing patient diversity in clinical trials
Diversity in clinical trials is an issue that the industry is consciously aware of and trying to solve, but action can often be slow. The development of personalised medicines requires solutions now.
Potential treatments that target specific proteins or genetic mutations could have life-changing benefits for those who are eligible, but it inevitably means a smaller patient population from which to recruit people into Phase III trials, making recruitment more challenging. To achieve meaningful patient diversity in clinical trials, we, as an industry, must put patients’ needs first. This involves identifying who they are and what they do, and developing appropriate and targeted plans to reach and educate them. By becoming more intentional in the way we approach and engage with patients, we can build relationships and trust across communities, helping to break down barriers and subsequently ensuring trials become fully representative of the patient population.
Clinical trial design
Effective patient recruitment begins with putting the patient perspective at the heart of clinical trial design. Studies should be built around patients’ needs and not just the treatment being investigated. A trial that has considered the challenges patients face and makes it as easy as possible for them to take part will find recruitment and retention a smoother process.
Patient-centricity also plays a key role in the development of patient materials. Too often, information is not presented in a way that engages with the intended patient population: it may not be in the most appropriate format or language, for example. Materials may also be lacking vital details that patients will want to know about, such as how many visits to the clinic will be necessary, if there are any associated costs involved and whether monitoring can be done at home.
Identifying and reaching eligible patients is not just about finding them in the clinic. Working with clinicians is a crucial part of patient recruitment for clinical trials, but so too is community engagement. Visiting communities where people live and work, and engaging with trusted community groups, leaders and healthcare professionals can often be a more effective tactic for patient recruitment, particularly for underrepresented ethnic groups.
It is often the case that clinical trial sites are under pressure to meet patient recruitment deadlines. A side effect of this is that patients can feel rushed into deciding whether or not to participate. It is important to remember that patients are people, and clinical trial participation can seem daunting. Allowing individuals time to come to a decision will result in more confident and engaged participants, especially when they also have access to patient-centric study information. In many cases this can help sites reach recruitment milestones more quickly.
Patient recruitment is a big task for any trial, but particularly for personalised medicines due to the smaller pool of eligible patients. Successful recruitment for these targeted therapies can therefore be more challenging. Working in partnership with an experienced vendor will enable the development and implementation of targeted and bespoke recruitment and retention strategies to ensure the right patients are recruited in adequate numbers within specified deadlines, giving trials the best chance of reaching their identified endpoints. In some cases, patient recruitment can be accelerated resulting in trial recruitment closing ahead of schedule. This not only reduces costs for trial sponsors, but will ultimately help get life-changing drugs to patients more quickly.
The growth of the personalised medicine market heralds new possibilities in healthcare, especially for those with rare and complex conditions. While diversity in research has always been a challenge for the sector, the rise of targeted therapies is necessitating a change in patient recruitment practices to ensure trials become more inclusive and representative of specific patient populations.
Strategies that put patients firmly at the heart of clinical trials will not only help to unlock the powerful potential of personalised medicines, but will begin to change the patient recruitment landscape of clinical trials as a whole.
1 – Grand View Research, Personalized Medicine Market Size, Share & Trends Analysis Report By Product (Personalized Medical Care, Personalized Nutrition & Wellness, DTC Diagnostics, Telemedicine, Complementary Medicine), And Segment Forecasts, 2021 – 2028, 2021 https://www.grandviewresearch.com/industry-analysis/personalized-medicine-market
2 – Pan D, Sze S, Minhas JS. The impact of ethnicity on clinical outcomes in COVID-19: a systematic review. EClinicalMedicine. 2020 doi: 10.1016/j.eclinm.2020.100404. published online June 3 https://doi.org/10.1016/j.eclinm.2020.100404
3 – A Ramamoorthy, MA Pacanowski, J Bull, L Zhang (2014). Racial/ethnic differences in drug disposition and response: Review of recently approved drugs. Clinical Pharmacology & Therapeutics. Doi: https://doi.org/10.1002/cpt.61
4 – Zucker, I., Prendergast, B.J. Sex differences in pharmacokinetics predict adverse drug reactions in women. Biol Sex Differ 11, 32 (2020). Doi: https://doi.org/10.1186/s13293-020-00308-5
5 – RP Symonds et al. Recruitment of ethnic minorities into cancer clinical trials: experience from the front lines. British Journal of Cancer. 2012. 107(7): 1017–1021. Doi: 10.1038/bjc.2012.240
6 – Pahus, L., Suehs, C.M., Halimi, L. et al. Patient distrust in pharmaceutical companies: an explanation for women under-representation in respiratory clinical trials?. BMC Med Ethics 21, 72 (2020). https://doi.org/10.1186/s12910-020-00509-y