Patient recruitment remains the biggest bottleneck in clinical research, and while some progress has been made in the last 10 years there is still much to be done
There has been an increase in competition for both patients and investigator sites – thanks in part to rising numbers, size and complexity of trials – and efforts to educate patients and physicians on the benefits of participating have only gone some way to solving the problem. It is estimated that more than 80 per cent of trials start late because of site selection and patient recruitment issues, and around half experience significant delays in completion.
In-house research conducted at contract research organisation (CRO) Quintiles suggests that 58 per cent of all patients are never offered trial participation, while external studies suggest it may be as high as 70 per cent, according to Chris Kula-Przezwanski of the firm’s health engagement and communications group. Meanwhile, Quintiles’ internal data shows that when patients are engaged, more than 70 per cent of them will enrol in a trial.
Clearly, there is an educational disconnect at play, and technology is one way to bridge the gap. In fact, digital has already had an impact on recruitment – with the internet, social media and other approaches helping to bring patients into trials at lower cost than physician-led enrolment, according to Brendan O’Neill, director of the patient strategy research group at Parexel.
Digital engagement with patients is rising fast, but there will always be a place for traditional approaches
“In 95 per cent of our programmes it is more cost-effective to recruit patients digitally, for example via online advertising and social media,” he says. The use of digital is also evolving – at one time it was often employed to help support trials that were not meeting enrolment targets, but latterly it is much more likely to be an integral part of the process.
Once a patient is in a digital system the benefits can be enormous. Beyond participation in trials, digital platforms can be harnessed to create a two-way dialogue, with patients receiving visit and medication reminders, study feedback, advice on managing symptoms and potentially other guidance such as videos on how to administer medicines properly. In turn, patients can be encouraged to stick with the trial and feed back information to the investigators.
The aim is to build a continuum for patients, according to O’Neill, so when they are diagnosed with a condition and start trying to learn about it on the Internet they can find information on clinical trials and are encouraged to opt in to participate.
At the moment digital recruitment is still emerging, despite early successes. Some contract research organisations – such as Quintiles with ClinicalResearch.com – are setting up their own portals and patient communities – using Facebook for example – to try to connect patients with clinical trials.
Quintiles has a head-start in this area thanks to its MediGuard.org database, which monitors the safety of medicines and – with 2.6 million consumers on board – is claimed to be the largest online drug community providing information on drug interactions and other safety issues. Launched in 2007, functionality was quickly added to that database to allow patients to opt in to being contacted about research opportunities.
Other initiatives include recruiting patients via relationships with websites operated by patient advocacy groups. One example of that approach is the PatientsLikeMe which encourages its 250,000 members to support each other, swap information and track their own health, as well as share their health data and participate in clinical trials. Information on ongoing studies is harvested from public databases such as clinicaltrials.gov.
Another approach gaining traction is that put forward by TrialReach, which tries to put patients at the heart of the recruitment process, with an open platform that enables any sponsor to upload trial details – free – and have them converted to lay language summaries and connected to patients seeking health information. Rather than setting up a restricted database, the platform partners with other healthcare information providers, such as patient.co.uk, placing its trial information in front of 45m people a month.
“The only scalable way to achieve this level of access is an open platform which presents information to the consumers in a place they already know and trust,” according to the company’s chief executive Pablo Graiver.
The delivery of clinical research information is certainly evolving fast, with a move away from websites to ‘capsules’ of information that can be disseminated across multiple digital platforms, irrespective of the carrier. That approach allows information to be shared in real time, allowing content to be tweaked to suit evolving circumstances, says O’Neill.
“What’s exciting for us is you can test materials on the fly, gauging how favourable a response is to particular messages and making real-time course corrections,” he notes.
Health records
One consequence of these different approaches is that the landscape for patients seeking information on trials is fragmented which – hypothetically – suggests even patients actively seeking trials may slip through the cracks or be anxious about enrolling in one portal versus another.
Many clinical researchers therefore see the endgame in this digitisation process as the routine recruitment of potential patients on the basis of electronic health records (EHR), which would have the additional benefit of also harvesting patients who may not choose to look for health information or trials online, whilst also injecting a valuable ‘real-world’ ingredient into clinical research.
At the moment, exploiting EHRs for clinical research purposes remains largely a matter of pilot studies, but some give glimmerings of promise.
For example, Quintiles has used its MediGuard platform alongside the SAIL (Secure Anonymised Information Linkage) databank in Wales to recruit and monitor patients with high cholesterol in an observational study. Enrolment of 250 patients took six weeks – using traditional approaches it likely would have taken months – and the pilot clearly showed that with proper governance it is feasible to use an EHR alongside patient-reported outcomes (PRO).
While the potential is clear, the reality at the moment is that there is a lack of standardisation on EHRs on a global or even regional basis, to allow these projects to be anything more than piecemeal and localised.
“EHRs were simply not built initially for clinical research purposes, so the types of data that you need to drill down to are not necessarily in the right format,” notes O’Neill. Some initiatives are however trying to tackle that issue, he adds. In Europe, for example, the four-year Electronic Health Records for Clinical Research (EHR4CR) project has brought together pharma companies, academic institutions and hospitals in a drive to demonstrate how data held within EHRs can be reused to enhance clinical research processes. The overall aim is deploy a common platform to gauge the feasibility of trial protocols, identify and recruit patients, help conduct trials and monitor serious adverse events.
Meanwhile, national initiatives are also being launched. Last year the UK Medical Research Council (MRC) promised to invest £20m to establish the health informatics-focused Farr Institute – with centres in London, Dundee, Manchester and Swansea – to develop ‘big data’ methods for safely sharing, combining and analysing health information.
Also in the UK, the care.data information-sharing initiative aims to create a nationwide database of anonymised medical records that could be used to monitor healthcare standards as well as help recruit patients into trials. The roll-out of the project was recently delayed however in order to tackle the issues of informed consent and patient confidentiality, which remain unresolved when considering the use of EHRs in trials.
National variations mean that what is acceptable in terms of consent in one market may not be in another, says Kula-Przezwanski. At one time, interpretation of the regulations in Germany for example indicated that informed consent required signatures on paper, even in the context of a digital recruitment programme.
“The use of EHRs is therefore raising a number of questions, such as is the data right, is it correct and can we use it. But this is a journey we have to take,” he points out.
It is also important to note that even while digital engagement by patients with health and trial information is widespread and rising fast, there will always be a place for the traditional approaches to patient recruitment.
“Right now, in some parts of the world such as Brazil, placing a poster on the door of the doctor’s office is still one of the most effective means of capturing patients because of the strong relationship between healthcare providers and patients,” says O’Neill.
Finally, while digital can help alleviate the patient recruitment bottleneck, it does not wholly address other issues such as competition for patients and the waning number of clinical investigators, driven out by the rising complexity of starting and carrying out studies. Company sponsors and CROs are now having to push hard to get a new generation of investigators on board; perhaps making patient recruitment more efficient will go some way to ameliorate that decline.
