As has been customary for just over a decade, the last day of February will see a tremendous amount of online engagement within the rare disease community. Rare Disease Day is a fixture in the calendar not only for affected patients and families, and patient advocacy organisations, but also the myriad of other stakeholders that make up the rare disease ecosystem. Researchers, pharmaceutical companies and regulatory bodies are all expected to get in on the action. And rightly so. With some 350 million people affected by a rare disease worldwide, an annual awareness day is needed just as much as those that shine a light on common medical conditions.

Even with the countless individuals around the world who devote their professional careers, their personal time, or perhaps even both to the fight against rare diseases, the challenges still loom large. There will be a lot of noise about rare diseases on the internet on February 29. But the job of getting new and effective treatments into the hands of all rare disease patients who need them cannot be achieved in a big-bang, once-a-year burst of activity.

For companies that help the pharmaceutical industry by generating insights from patient-experience data, long-term investment in online patient engagement is a strategic imperative. Trust takes years to build but can be lost in a matter of seconds. And as far as patients’ trust goes, it matters a great deal which part of the rare disease ecosystem you come from.

A 2018 survey by Eurordis, a non-governmental organisation representing rare disease-focused patient groups in Europe, underlined the patient community’s wariness towards sharing data with the private sector. While 79% of survey participants believed that researchers working for a non-profit organisation would handle their health information carefully, only 45% felt the same about researchers from a pharmaceutical or medical device company (https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1123-4).

Our recent experience in clinical trial recruitment has shown the benefits of long-term investment in trust building and online engagement. The 15 enquiries we received from members about a clinical study within the first few days of launching a referrals programme was the result of two things: one was pent-up demand within the patient community for new treatment options in an area of unmet medical need; the other was the time we invested in building and nurturing the relevant Raremark community in the three years since its launch. Clinical trial sponsors in rescue mode should note that such results would have been much harder to achieve from a cold start.

The engagement challenge is even more pertinent in longitudinal, data-collection projects, demand for which is growing as more pharma companies become switched on to the potential of real-world data (RWD). In this area of research, recruiting and onboarding participants is just the first hurdle. The bigger challenge lies in retaining as many of them as possible over time, to give us confidence that any findings are applicable to the broader patient population from which they are drawn.

Take a hypothetical study that onboards a group of patients who reflect the demographic composition of the overall US population. Low retention over a 12-month period might lead to a diminished and unrepresentative study sample, heavily skewed towards individuals sharing similar characteristics – mostly white people, women or those aged over 70, for example – raising concerns about the generalisability of the results.

Raremark’s first sponsored RWD study, focused on a rare gastrointestinal (GI) condition and conducted in 2018-2019, gave us an indication of the feasibility of retaining patients in longitudinal research projects over an extended period. Of the 44 patients who joined the study, 37 (84%) continued sharing their data throughout its six-month duration. The results showed that flare-ups of the condition were correlated with several aspects of patients’ lives, including financial outgoings, ability to take part in activities outside home, and the severity of key symptoms.

Yet recent academic papers that looked at data on participant retention in longitudinal studies conducted online (albeit not in rare disease) paint a less rosy picture. The Asthma Mobile Health Study, a large observational study for iPhone users, enrolled 7,593 individuals, 6,470 of whom completed at least one online survey. From this robust baseline cohort, just 175 users (2.7% of the baseline) chose to complete a milestone survey at the six-month time point (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559298/). A separate evaluation of eight remote digital health studies conducted between 2014-2019 (including the iPhone-enabled asthma one) found a median retention time of just 5.5 days out of a total possible 12 weeks (https://www.nature.com/articles/s41746-020-0224-8).

These numbers give us pause, since much of the excitement around using digital tools in longitudinal research studies assumes that they will take on the job of sending reminder emails, sharing results with participants and such other things that would otherwise be done by humans. In our 37-person RWD study in the rare GI condition, it was possible for our research team to do all this heavy lifting, including keeping tabs on which participants had completed surveys on time, and sending reminder emails directly to those who hadn’t. But this high-touch, manual approach to communications will not work when conducting longitudinal research projects at scale.

A systematic review of retention strategies in longitudinal cohort studies published between 2006-2016 was also instructive (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258319/). The researchers’ analysis compared the effectiveness of what they called emerging retention strategies (including the use of websites, social media and text messages) with established strategies. It turned out that studies employing a higher frequency of emerging strategies retained more participants. Another observation – that there was no difference in retention rates between studies using emerging strategies and those that used none – can be read in different ways. Within the 10-year period studied, digital tools didn’t prove to be any better than traditional methods at retaining participants in longitudinal studies. But equally, because digital tools were no worse than the established methods, it makes sense to deploy them on tasks that can be automated, freeing up researchers’ bandwidth to develop and evaluate more novel engagement strategies.

Given what the academic literature and published data are telling us about the challenges of getting long-term engagement right, all credit has to go to the smaller patient organisations that manage to serve their communities tirelessly day after day, in many cases with no or few professional staff and modest financial resources. Although these organisations’ remit is entirely different from Raremark’s, we can still take inspiration from them, remembering that success in helping patients and families deal with rare diseases has little to do with what happens in a flurry of multi-stakeholder activity on the last day February, and everything to do with building trust and engaging with our members consistently throughout the rest of the year.

Pete Chan is Head of Research & Analysis at Raremark.

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