The need for disruptive innovation in pharma has reached a precipice. In order to compete in the era of stratified medicine, cost-effectiveness considerations, and overall patient empowerment, the industry must rethink every aspect of the drug development continuum.
A number of recent studies have pointed to the rising complexity and costs of clinical research. Tufts Center for the Study of Drug Development found that a fifth of procedures in later-stage clinical trials are solely conducted to collect extraneous data, with the average cost of these procedures being greater than $1 million. On average, study timelines have to be doubled to meet enrolment levels across all therapeutic areas, and 37% of all research sites typically under-enrol patients (1).
In addition, years of valuable drug development time are lost due to the lack of patient engagement. Enrollment costs account for up to 40% of total US clinical research budgets, so the widespread delays that are inflating budgets have become a high value problem. Estimates put the loss of sales revenues a sponsor incurs per month delay in clinical trials at $40 million (2). Against this background, patient-centred drug development has become a hot-button issue.
The overwhelming majority of the 94 clinical executives who participated in a cross-industry research project carried out by eyeforpharma over the past six months argue that patient centricity can no longer just be viewed as an opportunity for commercial pharma.
Turning to patient centricity "is essential", says Francisco Leon, Vice President and Head, Immunology Translational Medicine at Janssen. "Patients serve as our inspiration and, in addition, they play an important part in ensuring we maintain our focus".
There is a growing recognition that, through technology and strategic process innovations, patient views and values must be integrated in new ways in drug development. Senior executives believe that for reduced development costs, and faster and more effective trials, patients must be "front and centre".
What if patients were viewed as collaborators in drug development, not sources of data".
Patient-centric innovation is going to be at the heart of the transformation of healthcare over the next couple of decades,” argues Miles Ayling, Director of Innovation at NHS England. As the patient’s role in healthcare has become more participatory than ever before, drug sponsors are re-examining traditional approaches. Yesterday’s trial subjects are increasingly seen as tomorrow’s lead customers. Patients in trials are becoming partners in research.
What if patients were viewed as collaborators in drug development, not sources of data?” asks Tom Krohn, Director of Clinical Open Innovation at Eli Lilly. Krohn is an advocate for redefining patient engagement in clinical trials from a consumer perspective. “What if they could explore what it was like to be in a study before they visited the site?”
Together with colleagues at Eli Lilly, Krohn has sought to integrate trials closer into patient lifestyles. In this vein, the company has improved the trial matchmaking processes, altered the tone and presentation of communications with patients, and tried to integrate the patient voice into study design. Ultimately, patient centricity entails “more than just the patient’s voice; it involves the patient’s thoughts, values, preferences, strengths and shortcomings” (3).
Patients do not join clinical trials to help pharma develop and commercialise new medicines. Analogously, the pharmaceutical industry does not sponsor clinical trials to treat sick people, but to bring drugs to market that cure diseases. In the past, trials have been understood purely in terms of the scientific data value they are designed to deliver.
In terms of disruptive innovation – displacing earlier technology to create a new market or value network – it is fair to say that to become patient centred, every aspect of the clinical trial journey has to be reformed. There needs to be a paradigm shift, a rethinking of trial procedures as we know them.
Ken Getz, Director for Sponsored Drug Research at Tufts, illustrates the difference: the established trial follows a linear, sequential and compartmentalised model, with vertical ownership, centralised risk and proprietary clinical data at the core. Patient-centred trials, in contrast, are multi-directional and interactive, following an integrated model with horizontal ownership and shared risk. They rely on flexible, adaptive and proactive designs. In this context, pragmatic trials and the use of Bayesian statistical methodologies hold potential for a more patient-friendly study experience (4).
There should be a reframing of each of the objectives of trials in the context of participants’ needs. That means, at least in the first instance, to see volunteers primarily as patients seeking treatment.
According to Colin Scott, Clinical Project Leader for Novartis Consumer Health, this should lead the industry to recognise long-term studies in later stages of development, primarily as an effective medical management tool (across a broad spectrum of chronic conditions). At the same time, “pharma needs to better understand how to reach out into largely untapped, close-knit and underserved patient communities, and work through independent pharmacies, charity clinics and community working groups,” adds Scott.
Practically improving clinical trial experiences might mean taking rather straightforward steps – for example, creating a video to explain clinical risks, or getting feedback on the length of forms so that they are easy to understand. Informed consent should not be obtained; it should be a collaborative process. Communicating with patients in an effective way is critical, as trials involve sharing complex information at a time when participants and their loved ones are highly vulnerable.
More study visits means more time off work for either patients or caregivers. There are other hidden costs that may not even be obvious but can have a significant impact on a patient’s overall experiences, such as sitting in a waiting room without hospital wi-fi . For many trials, the accumulation of slight inconveniences makes patients evaluate their participation in terms of overall costs and benefits. Unless the patient is in a very desperate disease status, those small factors can become decisive.
“You cannot just view participants as either in or out,” notes Paul Wicks, Vice President of Innovation at PatientsLikeMe. “It is not as though, after they sign an informed consent, they are yours for the next two years.” Across every touch point, patients make an active, conscious choice: every time they take a pill, fill out a questionnaire, or come to the hospital for a study visit.
Abandoning the Site?
If the safety of a drug is established, trials no longer need to be conducted in the controlled and sterile setting of a research site. Indeed, such an environment may very well provide the opposite of a genuinely patient-friendly atmosphere. So it is not surprising that eyeforpharma surveys have noticed an overall movement in clinical innovation away from a site-centric and towards a patient-centric environment. Current approaches range from increased in-home monitoring and tele-medicine, to trial setting virtualisation and data-driven intervention at the point of care (patient trial reminders in the doctor’s office).
There are multiple care settings in-between traditional research sites and patients’ homes that could potentially be leveraged. By bringing the study closer to the patient, the goal is to reduce the burden on participants and to boost enrollment, adherence and retention.
One objective of ‘direct to patient’ is to make clinical trials accessible to a larger community. The Novartis trial run at drug retailer Walgreens is the most prominent recent example of this. In late 2013, Novartis and Walgreens announced a partnership to run trials out of pharmacies, launching a study that should ultimately recruit up to 12,000 patients from 300 sites across the US.
The study is an example of pharma learning from Pfizer’s 2012 virtual study (the REMOTE trial), which was unsuccessful in the sponsor’s ambition to collect data directly from trial patients through social media channels like Facebook. The use of social media as a recruitment tool for trials has yet to demonstrate any tangible success – it is currently being used to recruit patients in only about 11% of all trials (5). More promising for patient engagement are dedicated sites such as PatientsLikeMe, MyHealthTeams, CureLauncher, or the tools developed by Transparency Life Sciences.
In November 2013, Pfizer, Eli Lilly and Novartis signed up as partners in an open innovation initiative to improve the US online registry, clinicaltrials.gov. The goal is to make the website more effective at matching patients to trials. The project marks an important progression from the era of manually identifying suitable clinical trials. By using electronic health records (EHRs), the aim is to devise a target health profile for each trial that is machine-readable, so that software can match patients to specific inclusion criteria.
These developments open up further advancements. Right now it is matchmaking from a patient-driven perspective. For instance, the US Government’s Blue Button standard – a symbol for patients to view online and download their own personal health records – only helps to match certain patient demographics to a certain trial, providing a map where users can look up a study in their neighborhood. Ultimately though, this tool could be used by a central organiser in the reverse.
Organisers that have access to the portal could try to find patients who would be suitable for a trial and reach out to them directly. This is highly targeted as there is no longer the need to post to a university hospital website, recruitment centre, etc. Instead, an EHR environment is leveraged. Such a process could be valuable given the development of personalised health, as well as helping to find patients in certain demographics.
Any change from web-based clinical trial portals, such as those being used to receive data, to pushing data out to physicians, payers or even patients directly, while technically feasible, is a long way off. At present, regulations restrict direct recruitment of patients where sponsors actively identify them through EHRs. With data privacy concerns growing more acute on a global scale, progress in this area will likely be gradual. However, the tools now exist to open up new avenues of patient recruitment.
A prevalent argument in the debate about patient-centred clinical trials is that initiatives in the areas outlined here rarely go far enough. As important as they are to initial focus areas, they may only result in incremental steps toward a more fundamental shift in the conception of drug development.
Furthermore, patient centricity and patient engagement have become buzzwords in pharma business speak, while many primarily talk about an updated approach to patient compliance. However, true patient centricity asks about how pharma can better comply with patients’ needs, rather than asking them to comply with pharma’s needs. For too long, patients have felt like the raw material in the clinical research process – nameless, experimental subjects generating reliable data.
Nonetheless, the clinical research industry has recently demonstrated a strong desire to engage with patients on an equal footing and take innovative steps to incorporate patient empowerment across the value chain of trials. The most successful examples of patient centricity place patients at the top of the trial management hierarchy – treating them as lead customers, including them in study design, and giving their decisions actual weight.
Some leading sponsors have demonstrated a keen vision to transform trials and place patients at the core of their research operations – a shift in mindset that may help fuel the next wave of patient-focused trial innovation.
In the context of lengthy and complex drug development schedules, regulatory requirements and ethical constraints, delivering wholesale transformation of the clinical research enterprise will be a challenging work in progress. But with the blockbuster model in question, and individual and personalised medicine on the horizon, the need for patient-focused innovation is as inevitable as opportunities for such change are staggering.
To start implementing patient centricity in clinical trials, join our Patient-Centered Clinical Trials on September 4-5, 2014 Boston.
1. Tufts Center for the Study of Drug Development, 89% of trials meet enrollment, but timelines slip, half of sites under-enrol, Impact Report 15(1), January/February 2013
2. Mintz C, Social media’s impact on clinical trial enrollment, Life Science Leader, 2010
3. Robbins DA, Curro FA and Fox CH, Defining patient-centricity opportunities, challenges and implications for clinical care and research, Therapeutic Innovation & Regulatory Science 47(3): pp349-355, 2013
4. Mullins CD, Vandigo J, Zheng Z and Wicks P, Patient-centredness in the design of clinical trials, Value in Health, 2014
5. Tufts Center for the Study of Drug Development, Drug developers circumspect about social media in clinical research, Impact Report16(2), March/April 2014
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