Arinesalingam Gnanasakthy

Assessment of PRO Label Claims Granted by the FDA as Compared to the EMA (2006–2010)

BACKGROUNDnThe US Food and Drug Administration (FDA) provides formal guidance for the use of patient-reported outcomes (PROs) in support of labeling claims, whereas the European Medicines Agency (EMA) offers insight in a reflection paper relating to health-related quality of life in lieu of formal guidance.nnnOBJECTIVESnPRO label claims granted for new molecular entities and biologic license applications from 2006 through 2010 were reviewed to evaluate consistencies and discrepancies in PRO label claims granted by the FDA and the EMA and to highlight trends in the acceptance of PRO claims across agencies.nnnMETHODSnProducts approved by both the FDA and the EMA were identified. By using US Drug Approval Packages and European Public Assessment Reports packages, any PRO label claims made for the same product by the same company were compared.nnnRESULTSnBoth agencies approved a total of 75 products. Of these, 35 (47%) had at least one EMA-granted PRO label claim compared with 14 (19%) by the FDA. Most FDA-grated claims focused on symptoms; however, EMA-granted claims were more likely to include higher order concepts. Few (~12%) were granted the same label claims. Despite this discordance between the two agencies, where PRO label claims were granted by both the FDA and the EMA, there was similarity in the type of label claim.nnnCONCLUSIONSnThe EMA is more likely than the FDA to grant PRO claims and for higher order constructs. On a macro level, there appears to be poor concordance between claims granted by both agencies. On close examination, however, there appears to be greater concordance than previously recognized, which may be instructive in formulating future PRO strategies. Further research to create strategic alignment across agencies may be beneficial.

Patient-reported outcomes, patient-reported information: From randomized controlled trials to the social web and beyond:

Internet communication is developing. Social networking sites enable patients to publish and receive communications very easily. Many stakeholders, including patients, are using these media to find new ways to make sense of diseases, to find and discuss treatments, and to give support to patients and their caregivers. We argue for a new definition of patient-reported information (PRI), which differs from the usual patient-reported outcomes (PRO). These new emergent data from the social web have important implications for decision making, at both an individual and a population level. We discuss new emergent technologies that will help aggregate this information and discuss how this will be assessed alongside the use of PROs in randomized controlled trials and how these new emergent data will be one facet of changing the relationship between the various stakeholders in achieving better co-created health.

US FDA patient-reported outcome guidance: great expectations and unintended consequences

Release of the US FDA patient-reported outcome (PRO) guidance raised expectations within the pharmaceutical industry for the use of PRO measures in support of labeling claims. The FDA developed the guidance with admirable intent, and the recommendations within this document are based on sound scientific principles. However, implementation of the guidance has been somewhat inconsistent within the Study Endpoints and Label Development (SEALD) and across the various FDA-reviewing divisions. Industry and regulatory bodies need to work toward gaining common ground to best support registration of treatments that could extend patients’ lives, reduce symptoms, and/or improve health-related quality of life. PROs are valuable tools in communicating these messages, and realistic implementation of the FDA PRO Guidance may truly facilitate this process.

Potential of patient-reported outcomes as nonprimary endpoints in clinical trials.

BackgroundThe purpose of this research was to fully explore the impact of endpoint type (primary vs. nonprimary) on decisions related to patient-reported outcome (PRO) labeling claims supported by PRO measures and to determine if nonprimary PRO endpoints are being fully optimized.This review examines the use of PROs as both primary and nonprimary endpoints in support of demonstration of treatment benefit of new molecular entities (NMEs) and biologic license applications (BLAs) in the United States in the years 2000 to 2012.MethodsAll NMEs and BLAs approved by the Food and Drug Administration (FDA) between January 2000 and June 2012 were identified using the FDA Drug Approval Reports Web page. Generic products granted tentative approvals were excluded. For all identified products, medical review sections from publicly available drug approval packages were reviewed to identify PRO endpoint status. Product labels (indication, clinical trials sections) were reviewed to determine the number and type of PRO claim.ResultsA total of 308 NMEs/BLAs were identified. Of these, 70 NMEs/BLAs (23%) were granted PRO claims. The majority of product claims were for disease- or condition-specific signs and symptoms. Of the 70 products with PRO claims, a PRO was a primary endpoint for the vast majority (57 [81%]). A total of 19 of the 70 products were granted a PRO claim based on a nonprimary endpoint. While nonprimary endpoints were used most often to support claims of improved signs or symptoms, nonprimary endpoints were much more likely to support claims of higher order impacts.ConclusionsSuccessful PRO labeling claims are typically based on primary endpoints assessing signs and symptoms. Based on this research, studies with PROs as primary endpoints are far more likely to facilitate positive regulatory review and acceptance of PROs in support of labeling claims. Although inclusion of PROs as nonprimary endpoints in clinical trials has its challenges, recent PRO labels granted by the FDA show that they can indeed be candidates for PRO labeling claims as long as they are supported by evidence.

Psychometric evaluation of the Sheehan Disability Scale in adult patients with attention-deficit/hyperactivity disorder

Inattention and impulsivity symptoms are common among adults with attention-deficit/hyperactivity disorder (ADHD), which can lead to difficulty concentrating, restlessness, difficulty completing tasks, disorganization, impatience, and impulsiveness. Many adults with ADHD find it difficult to focus and prioritize. Resulting outcomes, such as missed deadlines and forgotten engagements, may ultimately impact the ability to function at work, school, home, or in a social environment. The European Medicines Agency guidelines for evaluating medicinal products for ADHD recommend inclusion of both functional outcomes, such as school, social, or work functioning, and outcomes related to symptoms of ADHD in clinical studies of novel medication primary efficacy endpoints. Due to its performance in other disease areas and the relevance of its items as evidenced by content validity analyses, the Sheehan Disability Scale (SDS) was chosen to assess functional impairment in ADHD. The aim of this study was to investigate the psychometric properties of the SDS, used as a brief measure of functional impairment in a number of psychiatric disorders, in adult patients with ADHD. To the authors’ knowledge, this is the first study to evaluate the reliability of the SDS (based on Cronbach’s coefficient alpha and test-retest reliability), its validity (construct and known-groups validity), and its ability to detect change in this patient population. This study also established a preliminary responder definition for the SDS in this study population to determine when change can be considered clinically beneficial in a clinical trial setting. The psychometric results support the use of the SDS subscales (items 1–3) and total score (sum of items 1–3) in an ADHD population. In addition, the evaluation provides evidence for a three-point preliminary responder definition for the SDS and further evidence of its responsiveness in adults with ADHD. Altogether, the results indicate that the SDS is a simple and easy-to-score scale that would have great utility in future clinical trials for monitoring functional impairment in adults with ADHD.

PDB23: INVESTIGATOR AND SITE CHARACTERISTICS OF THE NAVIGATOR TRIAL

OBJECTIVES: To measure healthcare costs for patients receiving repaglinide, metformin, repaglinide/metformin, and glyburide/metformin within a managed care organization (MCO). METHODS: Using retrospective pharmacy and medical claims from a MCO, adult patients with type 2 diabetes identified during CY2000 were stratified into the following cohorts based on their medication regimen at identification date: repaglinide only (n = 500), metformin only (n = 26,535), repaglinide/metformin (n = 172), glyburide/metformin (n = 17,160). Pharmacy, medical, and total (pharmacy + medical) healthcare costs were measured for each cohort over a 9-month period. Costs were adjusted for age, gender, and comorbidities using Analysis of Covariance. RESULTS: Adjusted pharmacy costs were lowest for patients receiving metformin only (

PHP96 REASONS FOR REJECTION OF PRO LABEL CLAIMS: AN ANALYSIS BASED ON A REVIEW OF PRO USE AMONG NEW MOLECULAR ENTITIES AND BIOLOGIC LICENSE APPLICATIONS 2006-2010

1182; 95% CI

Correlations Between Changes in the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI) from Baseline to 28 or 40 Weeks: Comparisons of Trajectories of Change in Patients with Chronic Spontaneous/Idiopathic Urticaria (CSU/CIU)

1172–

Concordance of Pro Labeling Claims Between the Fda and Ema

1191), followed by metformin/glyburide (

PHP97 PRO LABEL CLAIMS: AN ANALYSIS BASED ON A REVIEW OF PROS AMONG NEW MOLECULAR ENTITIES AND BIOLOGIC LICENSE APPLICATIONS 2006-2010

1339; 95% CI