On March 7th 2018, Sanofi’s PRO Team attended the 5th Winter Symposium of the Human Motion Project. The vision of the project is to improve human health by an open collaborative technology platform for the mobile medical monitoring of human motion. The 2018 symposium focused on novel endpoints generated by mobile accelerometry for use in clinical trials. PRO research has highlighted the significance of reduced physical capacity to patients with chronic illness. Accelerometry is a technique for objectively quantifying movement patterns during walking and has more applicability in the real world compared to more traditional gait analysis or laboratory-based testing environment. However, its use in clinical trials has been restricted by questions around its sensitivity, specificity, precision and algorithms for analysis, as well as a lack of standardization of endpoints. The 5th Winter Symposium of the Human Motion Project included presentations and discussions focused on these topics. Specific topics included defining standards in accelerometer implementation and endpoints, testing of new algorithms for step detection and speed estimation, and linking accelerometer data to hard morbidity and mortality outcomes.
This is an important area for the future of clinical research and we are excited about developments allowing for more mainstream use and consistency in specification and interpretation.
On Dec 9-11, 2017, a member of Sanofi’s Department of Clinical Outcomes (CO) Team attended the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta, GA, USA. It was a great opportunity to gather information on hematological treatments and methodological advances in the hematology field; particularly hematological malignancies including multiple myeloma.
There were multiple presentations on patient perspectives, symptom experiences, health-related quality of life, financial burden, health economic models, resource utilization, costs, development of PROs, cost-effectiveness of treatment and economic burden of disease. Sanofi’s PRO Strategy for three Isatuximab studies were also discussed and presented at the meeting (ICARIA,IKEMA and IMROZ, NCT02990338, NCT03275285 and NCT03319667). In addition, the meeting provided information about cutting edge technology regarding treatment advances and measurement of the endpoints that matter to patients, providers, payers and employers; for example wearable devices to assess impact on and improvements in mobility and functionality due to disease and treatment.
The insights gained during this meeting will help us to develop clinical outcome, publication and reimbursement strategies at Sanofi.
In December 2017, a collaborative workshop was hosted by the Centers of Excellence in Regulatory Science and Innovation (CERSIs) and the Food and Drug Administration (FDA) titled “Advancing Use of Patient Preference Information as Scientific Evidence in Medical Product Evaluation”. The workshop aimed to discuss the current regulatory landscape for the collection, analysis, interpretation and presentation of patient preference information (PPI) and identify future research and capacity needs in order to improve the use of PPI in a regulatory context.
Plentiful research highlights that patients have unique perspectives about the value of the potential benefits and the impact of potential harms and burdens of their medical treatments. The consideration of patients’ needs, values and preferences is one of the core principles of evidence-based medicine, but reliable and accurate methods are needed in order to effectively incorporate these into the benefit-risk appraisal of a new technology. PPI is qualitative input or quantitative data elicited from patients to provide estimates of how much different outcomes, endpoints or other attributes are valued by patients, and the trade-offs that patients state or demonstrate they are willing to make among them.
The workshop focused primarily on eliciting PPI through stated preference methods - in which preferences are elicited by offering choices or posing contingent valuation questions to study participants - and revealed-preference methods in which patient preferences are obtained from the actual observed choices made by patients. Little discussion focused on qualitative data or data derived from quantitative patient-reported outcome instruments.
Matt Reaney from the Sanofi PRO team was invited to provide an industry perspective on eliciting and utilising PPI. Matt welcomed the discussion of PPI and its potential use in individual decision-making. He noted that industry regularly conducts research to elicit PPI in order to develop target product profiles and probability of success documents, inform unmet need and disease burden, make investment decisions, and define what constitutes a meaningful benefit. However, Matt did identify some challenges in generating robust data specifically for regulatory decision-making, namely:
In addition, there are some institutional challenges in generating PPI for regulators. For example, different methods may be utilised to answer different questions and qualitative research, stated or revealed preference studies, cross-over trial design, and PROs have traditionally been managed by separate domains in the industry. In order for the right method to be selected based on the question asked, knowledge of all “preference methods” would be required within a single function. External guidance documents outlining the utility of PPI data in principle, and the research requirements and evidentiary standards to inform the role of PPI in decision-making would assist in the provision of such a function. Matt’s comments were included in a media piece for Biocentury.
We hope that this workshop was the beginning of meaningful collaboration between patients, regulators, academics and industry in identifying how to make use of PPI in regulatory decision making – something which is important to all.
The International Quality of Life Research (ISOQOL) is a well-established non-profit society to advance the scientific study of health-related quality of life and other patient-centered outcomes to identify effective interventions, enhance the quality of health care and promote the health of populations. Sanofi representatives including one member of the Clinical Outcomes Team attended the 24th annual meeting held in Philadelphia, Pennsylvania US, October 18-21, 2017.
The Congress was themed “Embracing Complexity: Using Patient-Reported Outcomes to Generate Real World Evidence" andprovided a platform to discuss the challenges the field is facing with regards to theory, methodology and implementation of results in health care policy and clinical practice. Many presentations focused on oncology and spinal injury studies, although their methods were applicable to other therapeutic areas in general. Of the highlights of this congress were having a higher percentage of studies with focus to the adolescent and pediatric populations commonly less presented within the broad-based congresses.
The presentations were centered on the real world challenges of PRO-based clinical decision making, use of electronic PROs and interpretation of PRO data. Within the contextual consideration of developing and using electronic PROs, challenges of design, tool development, and implementation for both adults and pediatric populations were discussed. Overview of methods (parametric & none-parametric analyses), challenges and considerations in both quantitative and qualitative methods to interpret PRO data were topics, especially for clinically meaningful change and responder definitions.
The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) is a global scientific and educational organization for health economics and outcomes research. The team at Sanofi recently attended the 20th Annual European Congress to present and discuss research findings.
The congress was themed “the evolution of value in health care”; a timely reminder that definitions of value are changing, and an endorsement of the increasing role of patient organisations and representatives in defining value. This change is welcome and shows a progression often lacking in drug development research. However, the question of whether a clear and consistent definition of value can be provided and empirically supported remains open. Indeed it was apparent from presentations and discussions at the congress that some seek to embrace heterogeneity, while others seek simplicity and consistency. It is likely that in the future public and private organisations will come together to provide some clear guidance on defining value, outlining whose perspectives to embrace and when. Although the totality of this guidance remains unknown, it is clear that the patient perspective will be central to this.
In order to support this, the Clinical Outcome Assessment community at ISPOR and elsewhere need to think “bigger” than traditional quantitative outcomes. We need to embrace ways of engaging patients to understand experiences and perspectives beyond traditional endpoints. This will help ensure that we develop technologies to improve people’s lives, not just their health. The Sanofi team look forward to helping shape this movement.
The Clinical outcomes team at Sanofi, which advises on the conceptualisation, utilisation, development, analysis, translation, and interpretation of patient-reported outcomes and other clinical outcome assessments, has recently welcomed two new members to the team. The team is now represented in two US locations, and three European locations.
Both new team members are extremely experienced PRO Scientists who have a good understanding of the scientific principles that underpin subjective assessment, and have been involved in numerous pre-competitive research projects and collaborations to ensure interpretable capture of patient experience and patient outcome measures.
The Patient Engagement Advisory Committee (PEAC) to the US Food and Drug Administration (FDA) met on October 11-12, 2017 in Silver Springs, MD to discuss and make recommendations on patient input into clinical trials, with a specific focus on medical devices, despite being also relevant to drug development. The discussion topics included patient involvement in the design of clinical trials, patient recruitment, enrollment, retention and the communication of study results to trial participants.
Round table discussions with members of the FDA and the audience including industry, patients/patient representatives and research organizations took place to discuss patient involvement in clinical trials, recruitment, enrollment, retention, and dissemination of study results to trial participants and other patients. FDA representatives summarized the discussions at the end of each roundtable discussion.
Over the course of two days there were 16 open public hearing speakers that presented and provided comments to FDA. Speakers included patients, research organizations, industry, patient advocacy groups and other members of the public.
Key takeaways from the meeting included the importance of getting patient input into all aspects of medical device [drug] development and to consider patients as the end users of these devices [drugs], the importance of measuring patient-centric PROs (patient-reported outcomes that matter to the patient), and applying patient-centered solutions to patient-centered problems/questions regarding unmet needs, benefits and risks. Applying such strategies will bring products that matter to patients to market faster, and help to identify earlier in the development process products with higher risks to patients than benefits.
The meeting summary and presentations can be found on the PEAC meeting page.
Sanofi is proud to announce the development of a novel patient-reported outcome (PRO) in collaboration with Regeneron Pharmaceuticals Inc. that evaluates patient-centric attributes of statin intolerance in real-world setting. This brief questionnaire (15 items) was developed for patients with hypercholesterolemia that are at moderate, high or very high cardiovascular risk allowing them to foster a communication with their physicians regards their statin intolerance. Its development has met high methodology standards as outlined by the Food and Drug Administration (FDA)(FDA PRO guidance, Dec. 2009). Following an empirical literature review and perspectives from physicians and nurse practitioners, concept elicitation interviews were conducted with statin treated patients. Their symptoms and associated impacts were identified and selection of concepts for measurement and the construction of the questionnaire were determined. The questionnaire content was then subsequently tested for relevance, comprehensiveness, and suitability for use in real world. The psychometric analyses, including interpretability of scores is currently under investigation. This new PRO questionnaire is a welcome addition in cardiovascular field where statin intolerance needs better understanding from the patient perspective. Please visit the SEAQ page for detailed information !
In recent years the US Food and Drug Administration (FDA) have increasingly emphasised the importance of gathering the patient perspective in understanding disease and the potential benefits and risks of medications under development. Under the 2012 reauthorization of the Prescription Drug User Fee Act (PDUFA), FDA formalized the systematic gathering of the patients’ perspective through patient focused drug development (PFDD) meetings, of which 22 have been held to date. Under the recently approved 21st Century Cures Act, the FDA will further develop guidances regarding the collection of patient experience data, and the use of such data and related information in drug development. These guidances will outline the elicitation of information on disease status, impacts, and treatment experience, and the measurement of these in a standardized way which is clear, reliable, valid and responsive. Specifically, the 21st Century Cures Act requires that the guidances outline appropriate, relevant and objective methodological approaches to collecting patient experience data and identifying what is most important to patients with respect to burden of disease, burden of treatment, and the benefits and risks in the management of the patient’s disease; approaches to identifying and developing methods to measure impacts to patient, including clinical outcome assessments (and patient-reported outcomes [PROs]) for purposes of regulatory decision making; and how such information will be used in the structured risk-benefit assessment framework.
The FDA plans to develop several guidances within the next five years, including ones to “describe approaches to collecting comprehensive and representative patient and caregiver input on burden of disease and current therapy”, “describe processes and methodological approaches to development of holistic sets of impacts that are most important to patients”, “describe approaches to identifying and developing measures for an identified set of impacts which may facilitate collection of meaningful patient input in clinical trials”. A guidance on clinical outcome assessments which will revise or supplement the 2009 PRO guidance will also be developed in draft format by the third quarter of 2020.
These guidance documents, coupled with ongoing PFDD meetings, will help to ensure that patients are engaged throughout drug development and evaluation, and will provide clarity in the regulatory expectations from drug manufacturers. We anticipate that the role of PROs will be emphasised in order to collect quantitative (and qualitative) data directly from patients, and that they will play a more central role in regulatory decision making, which will serve to enhance the patient-centric nature of drug approvals.
Table 1 in the FDA release provides a summary of key steps FDA will take in developing these guidances over the next five years: https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM563618.pdf
Health Technology Assessment International (HTAi) is a global scientific and professional society for researchers, agencies, industry, academia, health service providers and patients/patient representatives who produce, use, or encounter, HTA to support optimal policy- and decision-making. The 14th Annual meeting took place in Rome on June 17-21 2017. Although the congress largely focused on epidemiology, health economics and modelling, there were some key sessions exploring timing of, and methods for, gathering and using the patient-, and societal-perspectives in HTA decision making. Sessions such as “Patient Involvement in HTA: Why, When and How”, moderated by Karen Facey from the University of Edinburgh, “Will the Patient-Centric Approach of Value-Based Health Care Drive Innovation in HTA?” moderated by Liesl Strachan from Medtronic, and “How to Measure Patient Preferences and Engage Patients in Value and Access Processes” moderated by Isabelle Moulon from the European Medicines Agency presented an overwhelmingly consistent message; that various perspectives need to be accounted for in the way that pharmaceutical drug development is conducted, and that patients, patient representatives, and society have a vital role in helping shape that development so as to generate outcomes which matter most to the users of the medicine.
Achieving this goal requires us to think beyond the traditional paradigm of pharmaceutical drug development so as to collect “real world” data, and to systematically incorporate numerous perspectives when designing research projects. Systematically gathering representative and generalizable patient and societal views is an important part of this and requires expertise in both qualitative research and quantitative research methods. Specifically, Patient Reported Outcome Measures (PROMs) will be a central part of this movement, but we need to acknowledge that people can only respond to the questions they are asked in PRO research. A supplemental qualitative component will help ensure that we are better able to contextualise the quantitative PRO data, and provide additional relevant information unrelated to the study outcomes per se, including study experience and potential use in routine practice.
More news coming soon…