Pseudo real-world environments
By: Volker Ronicke, PhD, MBA | September 15, 2016
Bringing treatment to patients earlier by de-risking therapeutic intervention.
The biopharma industry is all too familiar with the challenge to demonstrate therapeutic value of newly launched treatments, while at the same time achieving commercial success. This is where companies stand to benefit from integrating clinical and commercial planning prior to Phases II and III, providing a better roadmap for regulatory approval, successful launch, and market access.
Almost exclusive reliance on the classical drug development paradigm remains a major obstacle. Here the focus is on clinical efficacy in randomized clinical trials (RCTs), rather than clinical effectiveness in a routine treatment setting. This stands in the way of significantly shortening cycle times. RCTs can take a long time to complete and time is not a luxury that patients have, especially those living with rare, chronic or life-threatening diseases characterized by high unmet medical need.
Traditionally, after proof-of-concept (PoC) is demonstrated, developers give the ‘go’ signal to proceed to larger phase III development programs. However, the risk-benefit profile created during Phase III trials can lack comprehensiveness. These programs still involve relatively small patient sample sizes in comparison to the treatment population post launch. Biopharma, therefore, is unable to detect rare safety events in Phase III programs. Furthermore, based on our analysis most drugs fail during Phase III due to efficacy issues, rather than safety issues. One could argue therefore that there will not be meaningful additional safety insights from Phase III development programs and the additional clinical efficacy evidence is of limited value to achieve a fair reimbursement value. An earlier emphasis on generating outcomes evidence on clinical effectiveness might be required. Most players would consider this approach as too risky.
Given the limitations of the classical drug development paradigm, is there an approach that will deliver a benefit-risk profile more relevant to the real world patient situation? Quintiles Advisory Services has the view that there is – in the form of early conditional launches into pseudo real-world environments that have the additional advantage of bringing treatments to patients, rather than patients to treatments.
Previously we reflected on the concept of conditional launching, where a drug or treatment is conditionally approved provided that some strict conditions are met. One such condition could be deploying a powerful strategy for risk mitigation, where the value of the therapy is monitored in real-time within a pragmatic and close-to-reality trial.
Such a trial is conducted in a less restricted patient population, within a clinical setting that is close to routine patient treatment practice. The objective is to closely observe the patient population, to better understand the benefit-risk profile. This pseudo real-world environment can be adaptive, including iterations, to broaden the patient population studied as further evidence is gathered, enabling the risk-benefit profile to mature. It allows the collection of significant real-world evidence (RWE). We believe that this type of conditional launching will soon become the new normal, and the pseudo real-world environment design is well positioned to support it.
A pseudo real-world set-up only works with high connectivity and patient data density. It requires highly advanced technology to back it up. A 24/7 surveillance system for patients and their treatment reactions must be present to enable early detection of possible adverse drug reactions and allow for quick remediation. Access to electronic medical records of patients must be unobstructed. The same goes for communication lines between a patient centric network of prescribers, patients, caregivers, public healthcare trusts, regional or national public healthcare insurance, and private managed care organizations.
The use of mobile devices and sensors is non-negotiable. These technologies enable the seamless integration and analysis of data in real-time to allow developers and treatment administrators to uncover trends, safety signals and potential care pathways.
Fundamentally, the right use of wearables, mobile devices, sensors and other telemetric devices can have the impact to completely change the way care is delivered and trials are conducted. We can start to bring the treatment to patients, rather than the patients to treatment. The traditional model where patients frequently need to attend clinic visits rather receiving treatment at home may partially explain why medication adherence and clinical trial patient retention are frequently an issue in clinical trials.
Telemetrics can revolutionize how clinical trial patients are recruited and engaged, and we believe this is (or should be) the next generation of health digitization; a continuous yet remote delivery and integration of validated or non-validated data and RWE from multiple sources in real-time for the purpose of informing drug development.
This also complements the use of mobile technology and sensors in market authorization decision-making, allowing professionals in this function to perform a continuous detection of safety signals and open up a world of possibilities for pharmacovigilance.
In November 2015 Quintiles announced that it had contributed enhancements to the Apple ResearchKit platform; an application which makes it easier for researchers to gather data more frequently and accurately and enhances patient engagement in registries and clinical trials.
Technology breaks down many of the delay-causing barriers associated with the classic R&D processes. Our white paper, Breaking the constraints of the current development paradigm, discusses more of technology’s role in creating closely monitored, well-connected, data-driven pseudo-real-world-environments with a strong risk mitigation strategy. With the power of technology, the promising future of a progressive drug development paradigm is within our reach.