On July 12, 2019, one member of Sanofi’s Department of Clinical Outcomes Generation (COG) Team (virtually) attended the 4th Annual FDA-ASCO Workshop on PROs in Oncology which was held at the FDA in Silver Spring, MD.
The focus on the workshop was on physical function as an outcome measure in oncology-given that physical function (PF) is a key functional domain of health-related quality of life in oncology and is considered a well-defined clinical outcome important across cancer types. In addition, PF can be measured by both existing PRO tools as well as emerging wearable technologies.
Past FDA workshops have identified disease symptoms, symptomatic adverse events and physical function as core outcomes of interest for FDA product review and have reviewed the characteristics necessary for a PRO tool to be considered fit for purpose for regulatory decision making.
Workshop sessions focused on electronic PROs (ePRO) assessment, PROs/ePROs in clinical care, registries, pragmatic trials, and in the real-world, standardization of PRO data collection, COA tools, endpoints, analysis, and visualization of physical function in oncology for regulatory decision-making
The ICHE9 estimand guidelines were proposed as a framework to develop rigorous PRO endpoints, and to review medical products and approve PRO labeling. The use of PROs from RW settings and the use of patient experience data to inform product development and to inform FDA reviews was also discussed.
Minutes of the meeting can be found here: https://www.fda.gov/drugs/news-events-human-drugs/fda-asco-public-workshop-2019-clinical-outcome-assessments-cancer-clinical-trials-fourth-annual
Sanofi is proud to announce the availability of the Patient’s Qualitative Assessment of Treatment (PQAT) patient-reported outcome (PRO) questionnaire. The PQAT is a novel methodology that utilizes a mixed-methods approach, combining open-ended free-text questions (qualitative) and quantitative questions with fixed-choice response options. It asks patients about benefits and disadvantages experienced during clinical trials, and how patients balance these benefits and disadvantages when deciding whether or not to continue with treatment. The PQAT presents an opportunity to explore the value and utility of individualized treatment benefit-harm assessment, which is likely to be of interest to a wide range of stakeholders (including regulators, payers, healthcare professionals, and patients). This questionnaire was cognitively tested with patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), but items are generic enough to be used for any adult patients receiving drugs during clinical trials. Two versions exist, PQATv1 and PQATv2 including 4 and 6 items, respectively. Developed in US English, it was also linguistically validated in 6 languages.
Please visit the PQATv2 page for detailed information!
In the 2013 Guideline on Pharmaceutical Development of Medicines for Pediatric Use, the EMA highlighted the need to consider medicine acceptability to the patient throughout the pharmaceutical and clinical development of pediatric medicines. Sanofi is proud to announce the availability of the Pediatric Oral Medicine Acceptability Questionnaire (P-OMAQ) in two versions, for patients (P-OMAQ-P) and caregivers (P-OMAQ-C), evaluating pediatric acceptability of oral medicine formulations from the perspective of pediatric patients and their caregivers. These patient-reported outcome (PRO) and observer-reported outcome (ObsRO) questionnaires were simultaneously developed with pediatric participants aged 6-17 years and adult caregivers (aged ≥18 years) of pediatric patients aged 6 months to 17 years taking an oral medicine (liquid, powder and pill/tablet formulations). Following an empirical literature review, the conceptual model of pediatric acceptability released was refined by an advisory committee composed of clinicians, researchers, and measurement scientists. Then, combined concept elicitation and cognitive debriefing interviews were conducted using a draft version of the questionnaires with 48 pediatric patients and caregivers stratified by age and oral formulation type. The final P-OMAQ-P and P-OMAQ-C questionnaires include 12 and 19 items, respectively. They are designed to be self-completed by young people aged 8–17 years or caregivers of young people aged 6 months–17 years. Both versions have been developed in US English and are available with a 24-hour or a 7-day recall period. These unique content-valid questionnaires reflect the specific attributes of acceptability that are important to pediatric patients and their caregivers, such as happiness in terms of frequency, size, amount, smell, taste, ease to swallow, or willingness to continue.
In the context of pediatric clinical drug development, these new questionnaires can bring useful information that may facilitate approval, and marketing initiatives.
March 18, 2019
COG team members attended the FDA workshop held on March 18, 2019 on Enhancing the Incorporation of Patient Perspectives in Clinical Trials. The workshop was held to discuss patient, caregiver, industry, academia and practitioner perspectives regarding the challenges and concerns facing patients participating in clinical trials, and to share best practices. The meeting focused on the challenges and concerns facing patients. Some of the main themes/messages that emerged were to include patient perspective earlier in the drug development process and throughout the product lifecycle (consider patients as partners in the process), to ensure concepts that matter to patients are included when assessing the value of the products, especially regarding treatment and disease burden, and to more fully share information with patients who participate in clinical trials in lay language and in a timely fashion without jeopardizing or invalidating a study. Some patients expressed concerns about how to select/navigate clinical trials they might be eligible for, or when learning they are not eligible to a clinical trial due to exclusion criteria such as comorbidities, pre-existing conditions or because too healthy. The patient testimony by and on behalf of patients was powerful and called for relaxed eligibility criteria in cases where patients are out of treatment options. Theresa Mullin from FDA said that for all future studies we need to ensure concepts that matter most to patients are captured using standardized measures, to use more historical controls if and when possible, to quicken research timelines, and to relax inclusion/exclusion criteria while not compromising the integrity of the trials that could benefit both the research sponsors and the patients. The workshop was held as part of an FDA commitment included in PDUFA VI (the sixth authorization of the Prescription Drug User Fee Amendments of 2017). A link to meeting including agenda, presentations, and full recording of the meeting can be found here: https://www.ctti-clinicaltrials.org/briefing-room/meetings/enhancing-incorporation-patient-perspectives-clinical-trials
The Sanofi Clinical Outcome Generation team participated to the 3rd annual Patients as Partners Europe conference in London, which focuses on patients’ involvement throughout the entire medicines development life cycle to drive greater efficiencies in clinical research.
All sessions emphasized the essential role of patients as experts of their disease to improve clinical research during the whole medicine life cycle development.
The new Patient-Focused Medicines Development guidance was presented to highlight how and when patient engagement is impactful when using robust methodology, more than 150 activities with patients were identified.
Many pharma case studies were presented on how patients were involved in clinical development and trial initiatives, how patient input was implemented, challenges faced and outcomes resulted from these initiatives. In most of these presentations, patient organizations, patients and carers were on the podium to share their specific and meaningful experience.
Some specialized service companies were also present to share how we can improve patient recruitment and retention in clinical trials by bringing solutions to patients’ home rather than the traditional model at sites.
This was a full 2-day conference to make us think and work differently, not only FOR but WITH the patients!
Sanofi is proud to announce the availability of the Injection-Treatment Acceptance Questionnaire (I-TAQ) patient-reported outcome (PRO) questionnaire, developed in collaboration with Regeneron Pharmaceuticals Inc., and evaluating treatment acceptance with a subcutaneous injection therapy. This questionnaire was developed with patients at high cardiovascular (CV) risk who had experience of self-administering their treatment for lowering low-density lipoprotein cholesterol (LDL-C) via subcutaneous injection, and items are generic enough to be used for any adult patients using subcutaneous injections. Its development and validation have met high methodology standards as outlined by the FDA (FDA PRO guidance, Dec. 2009). Following a literature review, concept elicitation interviews were conducted with 29 patients and then cognitive debriefings. The i-TAQ includes 22 items grouped into five domains of Perceived efficacy, Acceptance of side effects, Injection self-efficacy, Injection convenience and Overall acceptance. During its psychometric validation, it was found to be a reliable and valid instrument in high CV risk patients using a subcutaneously administered treatment for LDL-C lowering. Developed in US English, it was also linguistically validated in more than 35 languages. Please visit the i-TAQ page for detailed information !
On Oct 15-16 2018, Sanofi colleagues from the Global Clinical Outcomes and Risk Benefit and Epidemiology teams attended the Patient Focused Drug Development (PFDD) Public Workshop at the FDA in Silver Spring, MD.
The purpose of the meeting was to obtain feedback from stakeholders on two FDA Guidance documents in development under the PFDD initiative entitled Methods to Identify What is Important to Patients (Guidance Document 2) and Selecting, Developing or Modifying a Fit-for-Purpose Clinical Outcome Assessment (COA) (Guidance Document 3).
Representatives from all divisions of FDA (CDER, CDRH, CBER), the Pharmaceutical and Biotech Industry, Public/private partnerships, Academia, Patients and Patient Advocacy Groups were represented to provide input on:
One of the key questions that was discussed and debated over the 2-day meeting related to the target audience for the guidance documents—specifically whether the guidance documents should be targeted at scientists working in the field of PFDD or at a broader audience. While the emphasis on robust measurement would not change the level of technical detail would differ.
The FDA is particularly interested in feedback on the presentation of the text/tables, examples regarding what has worked, what has not worked (lessons learned), how sponsors have modified a COA and how to best estimate clinically important changes at the individual level.
Sanofi will offer a response to assist FDA in finalization of these important guidance documents.
The 2018 DIA Study Endpoints Community conference was held in September in Bethesda, Maryland. The conference brought together health care professionals involved in the selecting, developing, analysing, and interpreting of study endpoints. The focus was on advancing the scientific development and evaluation of study endpoints and educating other health care professionals about these developments. The congress agenda was broad, but all sessions emphasised patient-centricity, which has afforded significant innovations in how patients can be involved in endpoint development and selection in the past few years. Of particular interest was discussion around whether regulatory, payer and patient perspectives on the value of study endpoints can align, and whether core outcome sets for consistent measurement and analysis would facilitate this alignment. Core outcome sets are being developed by numerous organisations, including the Center for Medical Technology Policy (CMTP) and the International Consortium for Health Outcome Measurement (ICHOM) and recently the FDA send a request for information to facilitate their consideration of the value of core outcome sets in certain disease areas. It will be interesting to see how this develops, and the central role of patient-reported outcome (PRO) measures in these. Another topic discussed in detail – and resonating with the Sanofi team - was the importance of measuring positive well-being; something which is rarely done. Rather we focus on the absence of negative well-being, which of course is not the same thing at all.
In collaboration with Mapi Research Trust, Sanofi is organizing a free educational webinar dedicated to the Perception of Anticoagulant Treatment Questionnaire (PACT-Q) on Thursday, September 27, 2018. The PACT-Q is a valid and reliable instrument that allows the assessment of patients' expectations and satisfaction regarding anticoagulant treatment, as well as their opinion about treatment convenience of use. The objective of this webinar is to present the rationale for developing the PACT-Q, its development and validation, and its conditions of use, as well as its description among other PRO questionnaires within the Sanofi PRO questionnaire website. Please register today to this event and join our expert webinar hosts from Sanofi and Mapi to gain insight into how the health research and pharmaceutical community can use the PACT-Q in clinical research studies.
A recent research paper highlights the heterogeneity in peoples opinions about their health status. A small qualitative study, published in Expert Review of Pharmacoeconomics & Outcomes Research, explored the personalised health perspectives of 14 adults with self-reported diagnoses of cardiovascular disease (CVD). People were asked to segment a 0-100 scale (from the EuroQol 5-dimension questionnaire) into sections to show the boundaries between their own definitions of “poor”, “fair”, “good” and “excellent” health. There was a notable variability in where people drew the boundaries; the poor-fair boundary ranged between 10 and 50; fair-good between 40 and 75; and good-excellent between 60 and 91.
Usually, when looking at PRO data, it is inherently assumed that a self-reported health score has the same meaning for all i.e. a score of 40 for three separate respondents would be indicative of the same level of health status. However, the above study suggests that if three respondents provided a rating of 40 on the scale, one may believe that their health was good, another fair, and the third, poor. Similarly, respondents providing a rating of 60 could consider themselves to be in excellent, good, or just fair overall health.
This finding underscores the challenges in interpreting self-reported health scores. The article proposes use of a personalised framework for gathering individual definitions of health and using this information to interpret clinical meaning of PRO data for an individual patient. We believe that this is essential if PROs are to provide informative and useful data to researchers, healthcare providers, regulators, and patients.
More news coming soon…