Rules of engagement - redefining the sponsor-CRO relationship

Patient centricity has become something of a mantra within clinical trials. Essentially referring to what happens when you design a service or solution around the patient, its implications are deceptively far-reaching. Compared with the classical model of clinical trials - in which patients have little say in how they're involved - a patient-centric trial has scope for better-written protocols, higher recruitment and better retention rates.

In one survey, 75% of pharmaceutical companies agreed that putting the patient at the heart of a trial was now the priority. The sentiment becomes apparent through a cursory look at their websites: AstraZeneca says "science and patients are at the heart of everything we do"; Sanofi notes it's "a global healthcare company focused on patient needs"; UCB claims to be "inspired by patients, driven by science"; and Novartis describes itself as "a global healthcare company... that provides solutions to address the evolving needs of patients worldwide".

Of course, if claims of putting the patient first are to be anything more than an impressive-sounding slogan, companies need to invest significant time and energy in working out a strategy. The phrase, after all, is relatively nebulous and can mean different things to different people. Perhaps it means soliciting - and really listening to - patient feedback in order to improve the trial design. Perhaps it means giving a patient control over their data through a personal health record system. Perhaps it simply means designing a high-quality trial and generating usable data, therefore ensuring each person's participation has made a genuine difference.

As patients strive to make their voices heard, not least through social media, the topic is becoming increasingly salient. With the clinical space evolving rapidly, new questions are arising all the time, and the industry is taking an encouragingly exploratory approach to finding answers.

As Timothy Garnett, chief medical officer at Eli Lilly, told eyeforpharma in 2014: "Patients need to become active partners, as opposed to passive participants. What factors make this an experience participants often don't want to repeat? How can we become more patient and investigator-friendly in an increasingly competitive environment?"

While these questions may keep pharma executives up at night, it's important to recognise that sponsors aren't the only ones shouldering the burden. Typically, these issues are seeping through to their industry partners too, creating challenges as well as opportunities for CROs.

As Ken Getz, director and associate professor from Tufts Center for the Study of Drug Development, explains, the push towards patient centricity is giving CROs a real chance to innovate. This, in turn, is subtly redefining the sponsor-CRO relationship.

"CROs are, in many respects, driving patient-centred innovations as they are eager to differentiate their capabilities," he explains. "These initiatives hold the potential through better feasibility and clinical relevance to accelerate cycle time, lower cost and, most importantly, improve success rates. Sponsors and CROs are keenly interested in implanting patient-centric initiatives that drive higher performance and efficiency."

Building bridges

Getz has undertaken an impressive body of work in this field. His core areas of research include drug development operating modes and their impact on performance, as well as patient-engagement tactics for CROs.

He says that for many forward-thinking CROs, the relationship with investigative sites is a major point of focus. In February 2015, Tufts Center for the Study of Drug Development hosted a round table for pharma and CRO executives. Participants overwhelmingly said they were looking to work more closely with clinical research sites - for example, by soliciting input on protocol design, sharing development plans and improving payment methods.

Many investigative sites feel somewhat distanced from the overall study, with a widespread perception that sponsors and CROs don't supply enough information. There is, therefore, a lot to be said for fostering a tighter relationship, with appropriate support mechanisms in place. After all, if different parties are working at cross-purposes, this will likely be to the detriment of the clinical trial.

Another area of exploration is big data. Through more sophisticated use of large structured and unstructured datasets, it will be easier for a CRO to determine patient characteristics, behaviour, attitudes and experiences.

"We're seeing the use of various technologies to improve the convenience of data collection, and increase patient involvement and retention, such as wearable devices and gamification applications," says Getz. "There are also e-consent solutions that improve informed consent comprehension."

Currently, these types of technologies are seeing their biggest impact in consumer healthcare. For instance, via smart fabrics, sensors, wristbands and watches that can log a person's health and fitness. However, as the technology evolves, we are seeing a wealth of new medical applications. Electrocardiogram monitors can now be used on the go, and smart pill technology (ingestibles) can monitor a patient wirelessly, even performing diagnostic imaging.

Today, a number of companies are working on sensors specifically for use in clinical trials. Google X, for example, is developing a wrist-worn health sensor that will be able to collect and analyse patient data to incorporate into a clinical trial data feed. While the work is still at its early stages - with data security and regulatory issues looming - it could give CROs real-time, objective information that would remove the need for intermittent testing.

Similarly, Medidata has teamed up with Garmin to better capture patient data in clinical trials. Through integrating Garmin's vivofit activity tracker with the Medidata Clinical Cloud, the cloud-based solutions provider hopes to connect information about sleep and calorie burn with traditional clinical measures. This may enable better insight into patient health status or response to therapy.

As these types of technologies gain traction, they will surely occasion a change in the way that studies are run. However, Getz believes that they are not responsible for the ongoing shift in attitudes.

"The technologies themselves are not disruptive, as they enhance processes," he says. "The real compelling and transforming change is in the philosophy to put the patient at the centre of drug development activity."

Perhaps the real driver for patient centricity is a shift within medicine. As current revolutions get under way - such as the advance of personalised medicine, gene therapies and regenerative medicine - large-scale clinical trials featuring a wide range of participants will no longer be up to the task. Instead, there will be a surge in smaller, more targeted clinical trials that focus on a very specific patient cohort. This will mean changes in the way that patients are recruited and study protocols are designed.

As this newer, hyper-individualised style of trial becomes more common, classical paradigms will not apply and trials will have to be designed on a case-by-case basis. This may mean patient feedback becomes more critical than ever.

Group think

Patient advocacy groups - which came to prominence in the 1980s at the start of the AIDS crisis - have long worked together with sponsors and regulatory agencies to review study protocols, and the rise of online platforms has further facilitated this process.

"Many sponsors are interacting with patient advocacy groups and gathering input on protocol designs through the use of live patient feedback and advisory panels, and through virtual, online feedback with patient communities," Getz explains.

Clearly, CROs can make a difference by soliciting patient input into protocol feasibility. "There are many initiatives, under way and planned, to integrate patient input," Getz continues. "Government organisations, regulatory agencies and public-private consortia - CTTI, EUPATI and PCORI, for example - are providing guidelines and frameworks to help protocol designers solicit and integrate the patient's voice. FDA has also been soliciting patient input into meaningful protocol endpoints and outcome measures for a number of rare diseases."

There may also be opportunities for CROs within the patient recruitment space, not least by using digital platforms. Regarded as the biggest bottleneck in clinical research, patient recruitment issues can cause a real headache for pharma companies: it is estimated that about 80% of trials start late because of recruitment issues and around half experience delays in completion.

In an ideal world, all relevant patients would be informed about upcoming clinical trials, and offered the chance to take part. The right technological solutions, such as online advertising and social media, could help enormously, bridging the educational divide and helping to match up studies with participants.

Social mobility

One study in 2012 demonstrated that social networks do indeed hold great potential for this purpose. A Facebook advert that ran for five months invited women aged 16-25 from Victoria, Australia, to participate in a health study. Of the 551 women who clicked on the ad, 426 agreed to undertake a health-related survey and 278 completed it. The researchers concluded that, given the low cost of advertising fees per compliant participant, the approach was "highly cost-effective".

Online advertising, however, is only a small piece of the puzzle. A number of CROs, including Quintiles, have set up their own digital portals to connect patients with appropriate clinical trials. These clinical trial search services aim to make it easier for patients to find studies and vice-versa, mostly by making existing information more user-friendly.

"If patients and their families are more aware of the opportunities that clinical research can provide, they will be better able to make informed decisions about participating in research and helping drive the development of new and better medicines," said Chris Cabell, head of global access to patients at Quintiles, when www.clinicalresearch.com launched in 2009.

Evidently, today's CROs have an important role to play in spearheading change. Through working on patient-engagement initiatives, they will be able to position themselves as innovators in a rapidly evolving domain. They can, therefore, carve a niche in an increasingly competitive marketplace.

While the benefits for CROs is clear, there will also be benefits for the trial. Through keeping the patient at the heart of a clinical study, sponsors and CROs stand to optimise the process, avoiding delays, boosting retention, building trust and even cutting costs. These issues look set to take centre stage in the years ahead.

"Patient centricity is a movement that, if supported and executed well, will mobilise sponsors and CROs to collaborate as a team with a singular focus on meeting currently unmet patient and study participant needs," says Getz. "Sponsors and CROs want to see higher levels of integration, more effective collaboration and communication, and better leverage of each party's contribution to the project requirements. Patient centricity holds the key to drive more effective collaboration."