The power of translation for rare disease research

A disease is classified as a rare disease if it affects fewer than 5 people in every 10,000.[1]

Yet, collectively, there are an estimated 7,000 rare diseases, affecting approximately 400 million people globally. So, while each individual one may be relatively rare, as a group, those with rare diseases actually make up about 5% of the entire global population! That’s a lot of people!

When it comes to research, development of treatments, trials, and general care, those with rare diseases offer quite a different prospect to the “average” patient group. Given the rarity of their respective diseases, these patients are overwhelmingly likely to be geographically and linguistically spread across the globe, meaning that any clinical research or trial involving them will necessarily be an international affair. Diversity of participation is a great thing from a research perspective. In fact, it’s something we often lament the lack of in the clinical trial space at large. But what if – as could happen in the case of a rare disease – every single person on your trial is from a different country and speaks a different language? In the rare disease space, there are global patient advocacy groups that lobby for trials relating to their diseases to even happen. So when these do come to pass, and given the opportunities for compassionate use these trials may entail, there is a good chance that people with the relevant disease from across the world will want to take part. How, then, do you handle the logistics of that?

Why is translation so important for rare disease research?

Providing information and communication in patients’ native language is important in any clinical trial and in healthcare in general, with several studies showing that “patients who face language barriers have poorer health outcomes compared with patients who speak the local language”.[2] But this is particularly true when it comes to rare diseases. In this arena, it’s essential for patients to really understand for themselves their disease, any discoveries, medications, and end-to-end information relating to clinical trials. Given the general lack of research and knowledge out there relating to their conditions, patients with rare diseases are often obliged to become advocates and experts for themselves and their community, and need to be able to make very well-informed decisions about their own health. Generally speaking, they cannot rely on guidance from the medical establishment in the same way as most patients can. As we’ve mentioned above, they may even be the ones to raise awareness of their disease and lobby for research to happen in the first place! Even at this upstream stage in the research process, therefore, translation has a significant role to play in helping global patient advocacy groups to collect information, speak, lobby, and convince in one voice and in the language required by the situation. This article offers some great examples of patient advocacy in action, including parents of children with muscular dystrophy submitting benefit-risk assessments directly to the FDA, and cystic fibrosis patients testifying to advisory committees on the impact of the disease and treatment drugs on their daily lives.

Once a group of patients have overcome the first hurdle, and successfully lobbied for research to take place in their disease area, the resulting trial faces the same challenges as any clinical trial, albeit with some different conditions. Let’s start with the recruitment and retention of participants. As discussed above, in some cases, the recruitment process could potentially benefit in certain ways from the disease under investigation being rare. For instance, patients with rare diseases (particularly those for whom treatments don’t yet exist) tend to be more willing to take part in research.[3] The other side of the coin, however, is that the pool of patients on whom you can draw for your recruitment is significantly smaller than average in these cases, and – depending on their location, the disease in question, and their circumstances, it may be difficult to reach the numbers you need for a trial. It can be tricky to get the message out, where this is necessary, to a geographically and sparsely dispersed patient population. But this is where having a translation partner with native people on the ground all over the world can be transformative! Conversis, for example, can cover over 330 language combinations through experts living in-country, who speak the language and understand the culture. This means you’ll be able to reach your target patients, speak to them in terms they understand, and make them feel seen and safe enough to work with you. To give just a few concrete examples, we have worked on whitepapers and webinars for Asia, surveys for Europe, and recruitment for diseases like Angelman Syndrome (which affects about 500k people worldwide[4]), Prader-Willi syndrome (about 400k people worldwide[5]), and Huntington’s disease (around 30k people in the US[6]).

What about patient retention?

The same basic factors have a significant impact on retention too. Given the recruitment pool and the logistical issues, once patients become participants, you really cannot afford (on a number of levels) for them to drop out. As we’ve discussed before, on average, about 30% of patients enrolled on clinical trials drop out, and it can cost around $19,500 to replace them. Imagine, then, the impact in a rare disease trial, where the scope for replacing dropouts is so much smaller and dropout rates can reach up to 67%![7] There are plenty of reasons patients with rare diseases may drop out of a trial; thankfully, the vast majority of them can be headed off by patient-centric approaches and clear, empathetic communication.

For instance, the wealth and diversity divides we see in general in clinical trials are likely to be even greater when it comes to rare diseases, given the heightened diversity of the participant pool. Where interventions need to happen on-site, this can pose major issues for participants who do not live in the country in which the trial is being conducted. It is likely to be much more practical for some patients than others to take time off work or to move to another country for a period. In the case of pediatric diseases, entire families may need to move! These patients – especially those with less disposable income and who do not speak the language of their host country – need practical and emotional support to handle this kind of travel. Without this, the stress of such a move could have a significant impact on retention. As this ACRP article puts it: “The complexities of managing travel logistics create emotional and financial burdens for the patients, who are already under physical and emotional stress. Many cannot contemplate participating in a trial because of these additional challenges”. Support, in this context – outside of the financial aspect – means native language assistance with travel and logistics; it means open lines of clear, localized communication; it means the opportunity to raise concerns with confidence (in one’s own language) and have them be understood and taken seriously. Where this kind of support is provided, it can make all the difference in the world – patient satisfaction improves[8], with consequent positive effects on adherence and retention.

Another way to boost retention is through DCT implementation, which reduces the need for on-site visits and travel, and the particular disruption those entail in a rare disease trial. Incorporating DCT elements into a trial has been shown to better support diverse participation, and to improve the retention of those diverse participants too. It’s extremely important to note here that consistent, quality localization of DCT elements is absolutely crucial to achieving the intended effects. Some studies suggest that no localization or poor localization of such elements can be actively harmful to participation and adherence of non-native speakers. Take the example given in the Journal of Immigrant and Minority Health, that “during the COVID-19 pandemic, Spanish-speaking patients were among the least likely to utilize telehealth and video visits in the United States”; a situation the authors suggest “could be because telehealth exacerbated the difficulties that Hispanic patients already faced when communicating with their providers”. On the other hand, DCT elements that are well-localized can reduce barriers to understanding and participation dramatically, providing meaningful support to a diverse patient pool.

The other ways translation helps

Other unique challenges and opportunities presented by rare disease research include the need to understand distinct national and regional regulations on a global scale. Navigating regulatory structures across multiple countries is greatly simplified by having native experts on the ground, who are embedded in the local culture and can advise and communicate on your behalf.

And then there’s the very language of rare diseases (or, in many cases, the lack thereof). The rarity of these diseases and the limited existing research can sometimes mean the terminology for a given disease simply does not exist outside the English language. This means you and your translation partner can effectively create this language during localization – giving people a vocabulary they previously did not have to talk about their lives and their illnesses. That’s a part of the job that never ceases to be rewarding!

Rare disease research is a further specialized niche within the already specialist domain of clinical research. As such, it comes with its own unique challenges and obstacles. However, success in this sphere can produce the kind of meaningful results not many people get to effect in their professional lives – potentially providing people with language, hope, and better health outcomes for themselves and their loved ones. What greater purpose could we possibly have to work towards?

If you’re in the rare disease space and would like advice and assistance on how translation can make your work more effective, please get in touch with Conversis. We are ready and excited to help you make a real difference!

[1] https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32000R0141&from=EN

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201401/

[3] https://link.springer.com/article/10.1007/s43441-023-00571-9

[4] https://www.angelman.org/what-is-as/

[5] https://www.uptodate.com/contents/prader-willi-syndrome-clinical-features-and-diagnosis

[6] https://rarediseases.org/rare-diseases/huntingtons-disease/#affected

[7] https://www.allucent.com/resources/blog/understanding-importance-location-rare-disease-studies

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667611/#CR15