Stakeholders throughout the drug development enterprise have caught the patient centricity bug and it is highly contagious. Sponsors, CROs, investigative sites, technology solution and service vendors, and ethical committees are all getting in on the movement, seeking new ways to enhance study volunteers’ participation experiences and to engage study volunteers and the broader health care community as partners in the research process.
This contagion is generating a large number of initiatives that touch all aspects of clinical trials; from design and planning, through study conduct and trial completion. Organizations widely believe that patient centricity holds the potential to transform traditional drug development R&D – a paradigm that has been highly productive but also highly risky, costly and inefficient. Let’s look at characteristics of the current R&D operating environment.
Traditional drug development
The number of new molecular and biologic entities in the R&D pipeline has been rising 7% annually and now exceeds 10,000 active drug candidates. And for each of the last several years, the total number of new drugs and biologics approved by regulatory agencies in the United States, European Union and Japan has generally met or exceeded historical approval patters of the past two decades.
Despite historical efforts to improve drug development risk, the high uncertainty of successfully bringing a drug from discovery to commercialization is low and getting worse. Recent Tufts Center for the Study of Drug Development (CSDD) research indicates that only 11% of drugs that enter clinical testing will be approved in the United States and Europe, down from a 16% success rate ten years ago.
Clinical phase durations are no faster today than they were in the early 1990s. Despite the implementation of numerous new practices and technology solutions intended to accelerate clinical development cycle times, the opposite has occurred. The average clinical phase duration is 6.8 years and has increased 15% during the past decade. Longer clinical phase durations are in large part a function of the therapeutic classes that dominate research activity (e.g., oncology and CNS) as drugs targeting these diseases require more time to demonstrate safety and efficacy.
Tufts CSDD research has also shown that development inefficiencies are also a function of rising protocol design complexity. The average number of procedures per protocol, average number of eligibility criteria, average number of investigative sites and countries where clinical trials are conducted simultaneously, have all increased dramatically during the past ten years creating more demanding protocols both scientifically and operationally.
Operating inefficiencies are a major contributor to longer development cycle times but perhaps the largest contributor is poor study volunteer recruitment and retention rates. A recent Tufts CSDD study of several hundred global clinical trials found that sponsor companies must typically double the planned enrollment period to give investigative sites enough time to recruit study volunteers and complete a given clinical trial. Even though study durations are extended, one out of every ten (11%) investigative sites, on average, in any multi-center global clinical trial will fail to enroll a single patient and one-out-of-four (39%) will under-enroll. The other half of sites in a given multicenter study will either eventually meet the enrollment target or will exceed it.
It is estimated that one out of every 200 people in mature markets (e.g., European Union, United States) would need to participate in clinical trials today if the clinical research portfolio were to be successfully completed. The failure of the drug development enterprise during the past two decades to elicit support and commitment from the public and patient communities and to engage them as partners in the clinical research process has played an instrumental role in challenging recruitment and retention effectiveness. National and international public opinion polls show that public confidence and trust in the clinical research enterprise has eroded. A notable percentage of the public believes that pharmaceutical and biotechnology companies are not transparent and do not share complete information about investigational treatments or inform the public quickly when safety concerns about a drug are uncovered.
The cost of R&D is high and rising. Total spending worldwide on pharmaceutical R&D will reach an estimated $140 billion (US$) in 2014, representing a 4.9% compound annual growth rate during the past ten years. 12 to 15 years of capitalized investment is required to bring a drug through R&D and into the marketplace. The average capitalized cost to bring a single drug through R&D and into the marketplace now exceeds $1.3 billion.
Each successful drug must cover its own direct costs (30% of the total) plus all of the costs associated with the high number of failed drugs and the opportunity cost of capital amortized over the R&D period. Today, most approved drugs are targeting smaller market opportunities forcing sponsors to implement a number of strategies to recoup high development investment (e.g., charging higher prices, generating revenue across multiple indication areas simultaneously, introducing companion diagnostics).
Putting the patient at the center of R&D
The current R&D operating environment is clearly inefficient, extremely risky and costly. A new paradigm is critically needed to drive higher levels of efficiency and to mitigate drug development risk. The concept of a patient centric R&D paradigm is compelling and potentially transformative and disruptive.
Under traditional drug development, pharmaceutical and biotechnology companies have vied to innovate in an insular and secretive manner. Sponsors have largely sought the development of medical interventions internally with a singular focus on performing great science to gather and analyze proprietary, competitively sensitive data.
In this approach, patients are subjects; contract research organizations (CROs) and investigative sites are service providers, and health care payers and providers are consumers of newly launched products.
Patient centered R&D seeks to engage patients and the health care community as partners in the R&D process. R&D innovation is an open process where precompetitive information and drug development risk is shared among a broader community of external partners including academic and basic research groups, co-development sponsors, development operations alliances, and patient advocacy groups.
Patient centered R&D strives to minimize research activity that does not target critical unmet medical needs as defined by the patient communities that innovations serve. In this paradigm drug development sponsors aspire to obtain commitment from study volunteers to support and to take ownership for clinical trials from design through to completion with the expectation that whatever is learned – both positive and negative results – will be shared openly to advance collective knowledge about disease and how to treat it.
As part of the patient centricity movement, clinical research professionals look to conduct not only great science, but also more feasible clinical trials that enhance study volunteer participation experiences and reduce the burden of participation. In this approach, contract research organizations, investigative sites, health care providers and payers each play important roles as R&D partners and supporters helping to ensure that patient participation experiences are positive and that patient medical needs are met.
Patient centric initiatives
During the past 24 months, as more organizations have turned their attention to this new paradigm, we have seen rapid proliferation of initiatives touching all aspects of clinical development. Sponsor organizations are partnering with patient advocacy groups and forming precompetitive alliances to better understand unmet medical needs, to collaboratively set research agendas, to generate financial and community backing of R&D initiatives, and to solicit input into protocol designs to improve feasibility.
Sponsors and CROs are establishing stronger relationships with a variety of health care delivery systems to leverage electronic health information. In doing so, companies hope to identify areas where medical interventions can be improved and better targeted, and to find and reach patients who might benefit by participating in clinical trials more rapidly and efficiently. Pharmaceutical companies and their contract research partners are piloting electronic informed consent forms and the use of wearable devices to improve the study volunteer experience and to simplify the collection of outcomes data in real time.
Sponsors and CROs are also piloting new approaches designed to make study participation more convenient. Telemedicine and home nursing networks, for example, are being used on select clinical trials to give patients the opportunity to participate in their own homes or in closer proximity to their residences and workplaces. By improving convenience, sponsors and CROs hope to increase study volunteer retention rates.
Partnership under a patient centric R&D model requires transparency and disclosure of clinical trial results to study volunteers and patient communities. A growing number of sponsors are now routinely disseminating clinical trial results, in lay language non-technical summaries, to volunteers at the completion of clinical studies.
Ultimately, patient centric drug development is expected to accelerate drug development cycle times, improve efficiency, and to spread R&D risk across multiple stakeholders through higher levels of clinical trial feasibility; better patient recruitment and retention rates; and broader support among all stakeholders impacted by new medical interventions. But it is early days and there is little to no information demonstrating real impact.
Over time, as more is learned, select initiatives will take hold and many will not. Some patient centric initiatives will deliver sufficient return on investment to affirm their becoming standard practice; some will be used on an as needed basis; and others will prove too costly with limited to no measurable benefit. At a minimum, the patient centricity movement is inspiring the drug development enterprise to challenge and transform the current R&D paradigm at a time when it is essential that it do so.
Author: Ken Getz, Director of Sponsored Programs, Tufts CSDD.
Read this and other articles exploring the key issues within Clinical Operations, Supply, Outsourcing and Technology in Arena International’s Clinical Trials Yearbook 2015.
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