Benoit Arnould

Bio: Benoit Arnould is an academic researcher. The author has contributed to research in topics: Formulary & Cronbach's alpha. The author has an hindex of 6, co-authored 8 publications receiving 462 citations.

PRO development: rigorous qualitative research as the crucial foundation

Abstract: Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity.

Patient‐reported outcomes and health‐related quality of life in effectiveness studies: pros and cons

Abstract: The importance of patient perspectives on disease impact and response to therapy is increasingly recognized. Patient-reported outcomes (PROs), including health-related quality of life (HRQL), provide information on the effectiveness of medical interventions that cannot be obtained using objective clinical measures. For drug development, PROs such as symptom questionnaires are accepted by the European Medicines Agency (EMEA) and US Food and Drug Administration (FDA) in the approval process. HRQL assessments can help to establish the niche for a new product to support marketing efforts. Utilities can also be derived from health outcomes measures for cost-effectiveness analyses required by health plans for granting drug reimbursement. Because they more closely reflect routine clinical care, effectiveness studies are often a superior setting than traditional randomized controlled trials (RCTs) for conducting comprehensive PRO assessments to determine the real-world impact of therapy on symptoms and other aspects of everyday life. Screening, quality of care, self-reported adherence to treatment, and patient monitoring are important potential applications of PROs in effectiveness studies. However, well-known limitations of effectiveness studies also apply to PROs; these sometimes include a lack of randomization, controls, and blinding. It may be difficult to obtain patient compliance and clinician assistance with PRO assessments in a real-world setting. PRO data may be biased by nonrandom patient dropout, errors in timing of PRO assessments, and the environment in which questionnaires are administered. Additionally, the drug development schedule often requires outcomes results before effectiveness studies can be conducted. Addressing these difficulties during study design and the use of short and targeted questionnaires will improve the usefulness and feasibility of PRO measures in effectiveness studies. Drug Dev. Res. 67:193–201, 2006. © 2006 Wiley-Liss, Inc.

The Role of Health-Related Quality of Life Data in the Drug Approval Processes in the US and Europe

Abstract: Objective: The objective of this research was to review the extent to which health-related quality of life (HR-QOL) and other patient-reported outcomes (PROs) have played a role in drug approval and labelling since 2006, when the US FDA issued its draft guidance on the use of PRO measures and the European Medicines Agency (EMA), its reflection paper on HR-QOL. Methods: This research was conducted through a systematic manual review of therapy area-specific regulatory guidelines (US and EU) and product labels issued during the period 1 January 2006 to 16 November 2010. Results: Fifteen (39.5% of all guidance documents) and 34 (35.8%) guidance documents containing recommendations for the inclusion of PRO endpoints in clinical trials were released by the FDA and the EMA, respectively. The FDAreferred to HR-QOL (as a secondary endpoint) in 3 of the 15 (20%) guidances. The EMA recommended use of HR-QOL endpoints in 22 of the 34 (65%) guidance documents. The FDA approved 93 products with PRO endpoints in labelling (out of 432 total approvals). Of those, eight products (8.6% of all products with a PRO claim) documented treatment benefits characterized as HR-QOL. The EMA approved 54 products that included PRO endpoints in labelling (out of 248 total approvals), of which 16 products (29.6% of all products with a PRO claim) reflected HR-QOL data. Conclusion: Our review shows that the patients’ perspective in clinical research is important for the EMA and FDA, with HR-QOL endpoints still playing a minor role in product claims. Our analysis suggests that the EMA’s receptivity to HR-QOL endpoints is greater than the FDA’s, and that both agencies value patient-reported symptom data. Differences between the agencies’ acceptance of PRO endpoints, especially HRQOL, might reflect differences in their structure and organization. As the world’s largest medical regulatory agency, the FDA employs an ‘army’ of experts to review submissions and develop guidance. This internal expertise enables the FDA to take an active role in defining endpoints, developing guidance and regulations that clarify their expectations, and enforcing regulatory policy. By contrast, the EMA, working with a network of over 4500 European experts, relies on clinicians and the scientific community for the definition of validity and the acceptance of an endpoint. Historically, the EMA has been more likely to accept existing measures, including global assessment and diaries, provided the assessments are supported by peer-reviewed publications of the development and validity of the instruments. Thus, the peer-review process and acceptance by the scientific and medical communities greatly influence the acceptance of PRO claims in EMA product approvals. Finally, the FDA’s stance may be driven, in part, by the potential use of PRO information in direct-to-consumer advertising and whether such measures are meaningful and interpretable by patients. For the future, we believe that the empowerment of patients in healthcare decision making will foster the use of specific PROs for evaluating the benefits of treatments on criteria that are meaningful to patients, in addition to traditional clinical endpoints.

To what degree are orphan drugs patient-centered? A review of the current state of clinical research in rare diseases.

Abstract: Over the past 30 years, the healthcare industry has increasingly turned its attention to rare diseases. Regulators have emphasized the need for clinical research in this area to be patient-centered. However, there is a lack of evidence concerning whether this need is actually met. In this paper, we aim to address this gap. First, we describe the state of patient-centricity in clinical research in rare diseases based on a targeted literature review. Second, we discuss recommendations from scientific bodies on patient-reported outcome (PRO) measures in rare diseases. Third, we analyze data collected from EMA’s and FDA’s websites concerning rare disease labeling claims and data from Clinicaltrials.gov concerning the use of PRO measures in rare disease pivotal trials. Fourth, we perform an exhaustive literature review on the use of PRO measures in the pharmaceutical industry, including all phases of clinical research, observational/registry studies, and instrument development and validation. There is limited information on rare disease patient engagement in study design, recruitment, and retention. None of the initiatives describing methods for developing PRO measures in rare diseases provide the clear guidance clinical researchers need. Only 17.4% of orphan drug labels contain a PRO measure. Less than half of pivotal trials in orphan drugs have a PRO measure as a primary or a secondary endpoint. Although the number of publications about PRO measures in rare diseases has risen in the past fifteen years, our results indicate that substantial improvements are needed to achieve patient-centricity. The nature and extent of patient engagement in rare disease research is under-documented. The current paradigm for developing and using PRO measures in clinical research is failing to meet the needs of rare disease patients. Not only are PROs rarely used as high-level endpoints in clinical trials or taken into account in labeling claims, they are also under-researched overall – there are too few measures for the multitude of rare diseases. We call for a clear guidance on patient engagement and suggest a realistic approach to the adaptation of PRO strategy to the specific context of clinical research in rare diseases.

Are We There Yet? Data Saturation in Qualitative Research

Abstract: Failure to reach data saturation has an impact on the quality of the research conducted and hampers content validity. The aim of a study should include what determines when data saturation is achieved, for a small study will reach saturation more rapidly than a larger study. Data saturation is reached when there is enough information to replicate the study when the ability to obtain additional new information has been attained, and when further coding is no longer feasible. The following article critiques two qualitative studies for data saturation: Wolcott (2004) and Landau and Drori (2008). Failure to reach data saturation has a negative impact on the validity on one’s research. The intended audience is novice student researchers. Keywords: Data Saturation, Triangulation, Interviews, Personal Lens, Bias.