Do you see the traditional model of R&D changing and, if so, how?
We are seeing a number of interesting trends. For example, we already see in oncology the use of ‘master protocols’ to enable multiple disease indications and/or multiple drugs to be evaluated simultaneously. Well-designed master protocols exploring multiple therapies within a single disease, a single treatment across multiple diseases, or multiple therapies across multiple disease indications or subtypes, promise to generate answers more rapidly and efficiently than the traditional clinical trial model.
This may be valuable in areas other than oncology, and in generating the evidence needed to support precision medicine. This adds a new level of complexity to clinical trial design and conduct.
We see a greater requirement for real-world evidence, often as a condition of post-marketing approval. While it is unclear what degree of real-world evidence can be generated in earlier phases of drug development, there is a clear desire to understand effectiveness in addition to efficacy to aid regulatory approval decisions. This will impact the way we conduct components of our development programmes in future, and we await FDA draft guidance on this topic in the coming years.
There is increased interest in patient-centricity – designing studies that are more convenient to participate in. Some of this involves changes in study design to enable place-shifting – conducting aspects of trials in alternative locations that are more convenient to the patient. Much of this is facilitated by the use of remote monitoring and telemedicine technologies, but also though leveraging local healthcare facilities such as pharmacies and health kiosks. This will impact the way we design and conduct traditional site -based studies.
Technology offers new, exciting approaches to treatment, and we should expect to be conducting clinical trials to assess the efficacy and safety of digiceuticals, such as mHealth solutions, in addition to traditional biopharmaceutical products. In addition, the testing of drug-device combinations, such as Ostuka’s digital pill (Abilify MyCite), may change the way we design and conduct studies in future to provide the evidence needed for regulatory decision-making.
In addition, we are seeing greater interest in collecting richer data from patients in free-living conditions to supplement our understanding of treatment effects. We see this, in particular, with the potential of using wearables and connected devices. This may lead to study design changes, and the development and validation of new gold-standard clinical endpoints.
Do you think patient-facing technology will play a greater role in clinical trials in future, and what can it achieve?
Absolutely. We are seeing increasing emphasis on patient-facing technology in all aspects of clinical trials. In particular, the collection of pertinent patient-reported outcomes has become a critical component of clinical trials – and more of this is now being conducted using electronic methods.
This is being driven by a number of factors. First, the screen-based technologies we use to collect eCOA data – smartphones and tablets – have become ubiquitous, with sites and patients becoming increasingly familiar and comfortable with their use. Currently 34 percent of the adult population globally has, or has access to, a smartphone.
Second, key regulatory guidance such as the FDA PRO Guidance (2009) has driven increased uptake of electronic solutions. It describes increased importance in demonstrating the timeliness of patient-reported data completion – something that is difficult to demonstrate without an electronic solution. This is mirrored in certain therapy-area specific guidance, such as the EMA asthma clinical trials guidance (2015).
Thirdly, there is a growing appreciation that patient-reported data provides meaningful information that complements other clinical and physiological information collected in clinic. Of course, patient-facing technology is broader than eCOA and we see an increasing role of other solutions that enhance the richness of data we can collect to understand treatment effects and remotely monitor patients, and to make trial participation more convenient – perhaps even reducing the need for as many in-clinic visits. While virtual trials are an exciting paradigm change, it’s more likely that elements of patient-facing technology that enable completely virtual trials will be increasingly leveraged in regular clinic-based studies to make trial participation more convenient and engaging, and to reduce rather than eliminate in-clinic visits.
Do you believe medicines developers are making the most of new technologies to improve their clinical research practices?
Some are, but we also operate in a highly regulated environment which can slow the adoption of new approaches, including new technologies. Newer approaches, such as the use of wearables to collect data to help understand treatment effects, are in the earlier parts of the adoption cycle. One of the barriers is understanding the regulatory position – knowing if data collected by these new technologies will be accepted by regulators in support of labelling claims.
Regulatory bodies are in general welcoming of the approach, but in the absence of formal guidance this can slow adoption. This is one of the reasons why the Critical Path Institute’s Electronic Patient-Reported Outcome (ePRO) Consortium has recently developed and published recommendations for appropriate evidence to support the use of wearable devices to collect outcomes data in clinical trials. Their work, and that of other industry groups such as DIA and CTTI, will help to drive adoption and become a catalyst for firm guidance from the regulators.
Could use of patient wearables for data collection address some of the issues faced by companies in getting their products past cost-appraisal barriers?
Wearables and connected devices provide a huge opportunity to better understand treatment effects, and to ensure the safety of trial participants through remote monitoring. There is little doubt that wearables offer the ability for insights that cannot be achieved though scheduled in-clinic assessments. For example, being able to measure daily tremor in Parkinson’s patients provides a more comprehensive picture of this important symptom than can be obtained through 2-weekly assessments in clinic.
Measuring free-living activity provides perhaps a more informative picture of whether patients are able to satisfactorily perform activities of daily living compared to a functional performance test conducted in clinic. Continuous glucose monitoring provides a rich understanding of blood glucose variability and post-prandial control, in comparison to average levels summarised by HbA1c levels.
This richer information will provide deeper insights to understand treatment effects, and may in future lead to enhanced labelling. It’s unlikely that this data will speed drug development, but they may certainly contribute to an earlier detailed knowledge and understanding of treatment effects, which may enhance go/no-go decision making.
Are there significant differences between the UK and the US in acceptance of wearable technology in clinical trials?
I don’t believe so. We see interest and pioneering work conducted by biopharmaceutical companies across the globe, and certainly on both sides of the pond. We know that FDA have an active interest in how new technologies such as wearable devices can be used in clinical trials.
In 2015, they issued a notice requesting comments on a public docket: Using Technologies and Innovative Methods to Conduct Food and Drug Administration-Regulated Clinical Investigations of Investigational Drugs. This demonstrates their interest in this growing area. In Europe, the European Commission has recently issued a call for proposals to contribute to a €50 million research project to validate clinical endpoints of mobility measured from accelerometers in free-living conditions. All these initiatives are positive signals that there is significant interest in how to appropriately leverage the potential offered by wearable devices in clinical research to add to our understanding of treatment effects.
What do you hope to achieve in your role at CRF Health?
We are seeing an explosion of innovation in the area of patient-facing web, mobile and wearable/sensor technology – applied in research, routine care and personal wellness. This makes it an exciting time to join CRF Health and to help define strategy on how we leverage innovations, and develop new solutions, to ensure we are able to provide the best means of conducting trials and measuring health outcomes in clinical research.
I’m excited to join an organisation with a strong product heritage, a background in good science and deep regulatory knowledge, and a commitment to continued development of products and services to benefit patient-facing clinical research. I will be looking to bring together science and technology to help develop new, innovative and enhanced solutions for patient-facing technology and data collection in clinical trials.
What has been your greatest professional challenge to date?
In terms of product development, I’m certainly proud of some of the innovative new products I have shaped – from trial supply simulation, converged EDC-RTSM solutions, an integrated eClinical suite including single sign on and novel disease management applications for pharmaceutical brand support programmes. But, I have a strong scientific background and as a scientist I’m also proud of some of the recent work I have led and driven including published studies to support the measurement equivalence of patient-reported outcome measures when using the subject’s own mobile device (BYOD – bring your own device); and with the ePRO Consortium on evidentiary requirements for the use of wearables in clinical trials. This latter piece was discussed favourably with FDA representatives at a Critical Path Innovation Meeting at Silver Spring last autumn.
