Adam Gater

Adherence to oral tyrosine kinase inhibitor therapies in chronic myeloid leukemia

Ensuring adherence to therapy is a challenge in chronic diseases, particularly in cancers such as chronic myeloid leukemia (CML), where there has been increased availability and use of oral formulations. A conceptual model of adherence was developed based on findings from a comprehensive literature review, to inform strategies for improving adherence to oral CML therapies. A complex interplay of factors (including clinical, psychological and behavioural) influence adherence to such therapies. Healthcare professionals have a key role in promoting and facilitating adherence and future strategies should place greater emphasis on understanding patient-level experiences in order to create personalized solutions.

The humanistic, economic and societal burden of Herpes Zoster in Europe: a critical review.

BackgroundHerpes zoster (HZ) or “shingles” is common in persons aged 50 years or over. HZ is characterised by a painful dermatological rash which typically resolves in approximately one month. Persistent pain for months or years after rash onset, however, is a common complication of HZ; referred to as post-herpetic neuralgia (PHN). Both HZ and PHN have a significant impact on patients’ lives, with considerable implications for healthcare systems and wider society. The aim of the present review is to provide comprehensive documentation and critical appraisal of published data concerning the humanistic, economic and societal burden of HZ in Europe.MethodsSystematic literature searches were conducted in Medline, EMBASE, PsycINFO, EconLit, HEED and CRD databases. Searches were conducted in July 2014 and restricted to articles published in the past 20 years. Articles were selected for full review by two independent researchers in accordance with predefined eligibility criteria.ResultsFrom a review of 1619 abstracts, 53 eligible articles, were identified which reported data concerning healthcare resource use (n = 38), direct costs (n = 20), indirect costs (n = 16), total costs (n = 10) and impact on health-related quality of life (HRQoL) (n = 21). Findings highlight that PHN is associated with greater impairments in HRQoL and higher costs of management than HZ. For both HZ and PHN, pain severity is a significant predictor of impact on individuals, healthcare systems and society. While the incidence of HZ and PHN increase with age, age does not appear to be a key driver of overall costs for HZ and PHN. Specifically, while direct costs (e.g. GP, specialists, medications, hospitalisations) tend to be higher for older patients, indirect costs (e.g. work time missed) are higher for younger patients.ConclusionsAvailable evidence highlights that HZ and PHN result in significant humanistic and economic burden for patients, healthcare systems and wider societies. A tendency to focus upon healthcare resource use and the direct costs of management at the expense of other impacts (e.g. informal caregivers and formal social care) may result in an underestimation of the true burden of HZ and PHN.

Assessing the Impact of Caring for a Person with Schizophrenia: Development of the Schizophrenia Caregiver Questionnaire

AbstractBackgroundThe responsibilities of caring for a person with schizophrenia may significantly impact informal caregivers’ lives. The Zarit Burden Interview (ZBI) was originally developed to assess burden among caregivers of people with Alzheimer’s disease.ObjectiveThis research was conducted to inform the development of a revised version of the ZBI, relevant to caregivers of people with schizophrenia.MethodsBased on published qualitative research, the questionnaire was reviewed and modified in accordance with industry-standard guidelines. The resulting questionnaire [the Schizophrenia Caregiver Questionnaire (SCQ)] was then completed by 19 caregivers during cognitive debriefing interviews to assess understanding, relevance and comprehensiveness.ResultsReview of the ZBI resulted in a number of operational changes to improve face validity and potential sensitivity. Further questions were added based on key concepts identified in existing literature and minor phrasing alterations were made to improve content validity. Findings from caregiver interviews supported the content validity of the SCQ.ConclusionThe SCQ provides a comprehensive view of caregivers’ subjective experiences of caregiving and demonstrated strong face and content validity. The questionnaire will be important in both clinical assessment and evaluating the efficacy of interventions designed to reduce or alleviate caregiver burden. Future research will seek to establish the psychometric validity of the questionnaire.

An instrument assessing satisfaction with iron chelation therapy: Psychometric testing from an open-label clinical trial

IntroductionThe Satisfaction with Iron Chelation Therapy (SICT) instrument was developed based on a literature review, in-depth patient and clinician interviews, and cognitive debriefing interviews. An, open-label, single arm, multicenter trial evaluating the efficacy and safety of deferasirox in patients diagnosed with transfusion-dependent iron overload, provided an opportunity to assess the psychometric measurement properties of the instrument.MethodsPsychometric analyses were performed using data at baseline from 273 patients with a range of transfusion-dependent iron overload conditions who were participating in a multinational study. Responsiveness was further evaluated for all patients who also had subsequent satisfaction domain scores collected at week 4.ResultsBaseline SICT domain scores had acceptable floor and ceiling effects and internal consistency reliability (Cronbach’s alpha: 0.75–0.85). Item discriminant and item convergent validity were both excellent although one item in each analysis did not meet the specified criterion. Small to moderate correlations were observed between SICT and Short Form 36 Health Survey (SF-36) domain scores. Patients with the highest levels of serum ferritin at baseline (>3100 ng/mL) were the least satisfied about the Perceived Effectiveness of ICT and vice versa. Satisfaction improved in all patients, although there were no clear differences observed between groups of patients defined according to changes in serum ferritin levels from baseline to week 4 (stable, improved, or worsened).ConclusionsThe SICT domains are reliable and valid. Further testing using a more specific criterion (such as assessing patient global ratings of change in satisfaction domains that correspond to the SICT domains) could help to establish with greater confidence the responsiveness of the instrument.

Development of a conceptual model evaluating the humanistic and economic burden of Crohn’s disease: implications for patient-reported outcomes measurement and economic evaluation

The primary objective of this review is to develop a conceptual model for Crohn’s disease (CD) outlining the disease burden for patients, healthcare systems and wider society, as reported in the scientific literature. A search was conducted using MEDLINE, PsycINFO, EconLit, Health Economic Evaluation Database and Centre for Reviews and Dissemination databases. Patient-reported outcome (PRO) measures widely used in CD were reviewed according to the US FDA PRO Guidance for Industry. The resulting conceptual model highlights the characterization of CD by gastrointestinal disturbances, extra-intestinal and systemic symptoms. These symptoms impact physical functioning, ability to complete daily activities, emotional wellbeing, social functioning, sexual functioning and ability to work. Gaps in conceptual coverage and evidence of reliability and validity for some PRO measures were noted. Review findings also highlight the substantial direct and indirect costs associated with CD. Evidence from the literature confirms the substantial burden of CD to patients and wider society; however, future research is still needed to further understand burden from the perspective of patients and to accurately understand the economic burden of disease. Challenges with existing PRO measures also suggest the need for future research to refine or develop new measures.

Challenges in quantifying the patient-reported burden of herpes zoster and post-herpetic neuralgia in the UK: learnings from the Zoster Quality of Life (ZQOL) study

BackgroundAcute presentation of herpes zoster (HZ) and the subsequent development of post-herpetic neuralgia (PHN) can have a significant impact on patients’ lives. To date, evidence regarding the human and economic burden of HZ and PHN in the UK is limited. To address this knowledge gap a national, multicentre, large-scale real-world study was conducted to inform the scientific community and healthcare decision-makers. This paper outlines difficulties encountered and challenges to conducting real-world studies in the UK, methods used to overcome these hurdles and strategies that can be employed to promote and facilitate the conduct of future studies.FindingsThe Zoster Quality of Life (ZQOL) study is the first UK-wide and largest observational study investigating patient burden associated with HZ and PHN. A total of 383 patients (229 HZ; 154 PHN) over the age of 50 years were recruited from 42 primary and secondary/tertiary care centres. Patient-reported outcome (PRO) assessments of pain, quality of life and treatment satisfaction were completed by all participants and supplemented by clinical information from participating physicians.Key challenges encountered during the conduct of this study can be broadly categorised as follows: 1) identification of centres willing/able to participate in the study: lack of resources and limited research experience were major barriers to recruitment of centres for participation in the study; 2) obtaining local research & development (R&D) approval: lack of clearly defined processes and requirements specific to real-world studies and limited degree of standardisation between R&D departments in approval procedures led to significant variability in submission requirements and lead times for obtaining approval; 3) recruitment of study participants: rates of recruitment were slower than anticipated, meaning it was necessary to extend the study recruitment period and increase the number of participating centres.DiscussionInitiatives designed to promote and facilitate the conduct of research in the UK are important for real-world studies. The ZQOL study shows that opportunities exist for real-word research. However, streamlining the R&D approval process where possible and further incentivising the participation of primary care centres in such studies would help to further facilitate the generation of real-world evidence to inform healthcare decisions.

Assessing Asthma Symptoms in Adolescents and Adults: Qualitative Research Supporting Development of the Asthma Daily Symptom Diary

BACKGROUND Despite the widespread availability of patient-reported asthma questionnaires, instruments developed in accordance with present regulatory expectations are lacking. To address this gap, the Patient-Reported Outcome (PRO) Consortiums Asthma Working Group has developed a patient-reported asthma daily symptom diary (ADSD) for use in clinical research to assess outcomes and support medical product labeling claims in adults and adolescents with asthma. OBJECTIVES To summarize the qualitative research conducted to inform the initial development of the ADSD and to provide evidence for content validity of the instrument in accordance with the Food and Drug Administrations PRO Guidance. METHODS Research informing the initial development and confirming the content validity of the ADSD is summarized. This comprised a review of published qualitative research, semi-structured concept elicitation interviews (n = 55), and cognitive interviews (n = 65) with a diverse and representative sample of adults and adolescents with a clinician-confirmed diagnosis of asthma in the United States to understand the asthma symptom experience and to assess the relevance and understanding of the newly developed ADSD. RESULTS From the qualitative literature review and concept elicitation interviews, eight core asthma symptoms emerged. These were broadly categorized as breathing symptoms (difficulty breathing, shortness of breath, and wheezing), chest symptoms (chest tightness, chest pain, and pressure/weight on chest), and cough symptoms (cough and the presence of mucus/phlegm). Conceptual saturation was achieved and differences in the experience of participants according to socio-demographic or clinical characteristics were not observed. Subsequent testing of the ADSD confirmed participant relevance and understanding. CONCLUSIONS The ADSD is a new patient-reported asthma symptom diary developed in accordance with the Food and Drug Administrations PRO Guidance. Evidence to date supports the content validity of the instrument. Item performance, reliability, and construct validity will be assessed in future quantitative research.

Health-Related Quality Of Life And Treatment Satisfaction Among Patients Receiving Novel Anti-Androgen Therapies For The Treatment Of Metastatic Castrate-Resistant Prostate Cancer (Mcrpc).

PCN237 HealtH-Related Quality Of life aNd tReatmeNt SatiSfaCtiON amONg PatieNtS ReCeiviNg NOvel aNti-aNdROgeN tHeRaPieS fOR tHe tReatmeNt Of metaStatiC CaStRate-ReSiStaNt PROState CaNCeR (mCRPC) Dearden L1, Shalet N2, Artenie C3, Mills A3, Gater A4, Grant L4, Jackson C3 1Janssen EMEA HEMAR, High Wycombe, UK, 2Janssen, High Wycombe, UK, 3Adelphi Research UK, Bollington, UK, 4Adelphi Values Ltd, Bollington, UK Objectives: Abiraterone acetate and enzalutamide, novel anti-androgen therapies with distinct modes of action for the treatment of metastatic castration-resistant prostate cancer (mCRPC), are approved in both the pre-chemotherapy and postchemotherapy settings. These anti-androgen therapies have significantly improved outcomes among mCRPC patients. However, to date there is little published evidence regarding patients’ real-world experience of these therapies in both the pre-chemotherapy or post-chemotherapy settings, particularly in terms of health-related quality of life (HRQoL) and treatment satisfaction. MethOds: Qualitative face-toface interviews were conducted with mCRPC patients (n= 38) and carers (n= 12) to obtain in-depth data concerning the patient experience with novel anti-androgen therapy. This included patients with experience of abiraterone acetate or enzalutamide in either the pre-chemotherapy or post-chemotherapy setting in France, Germany and the UK. Findings from this study have been used to inform the design of a larger quantitative, multinational online survey to further explore and quantify HRQoL and treatment satisfaction among mCRPC patients receiving anti-androgen therapy. Results: Patients generally had high expectations at initiation of therapy with a primary emphasis on reduction in prostate-specific antigen levels and improvements in HRQoL. Patients and carers reported that experiences on treatment had met or exceeded expectations. Administration procedures appeared to be of limited concern for patients and only mentioned by patients when prompted by directive questions. In particular, the need to take abiraterone acetate on an empty stomach was not deemed problematic. Some differences in the patient experience (e.g. side effects) and HRQoL of patients receiving abiraterone acetate and enzalutamide were noted and warrant further exploration. cOnclusiOns: Patients and carers reported largely positive experiences with novel anti-androgen therapies for the treatment of mCRPC. Potential differences between regimens in terms of treatment satisfaction and HRQoL are currently being explored in a larger quantitative online study.

The Potential Role of Individual-Level Benefit-Risk Assessment in Treatment Decision Making: A DIA Study Endpoints Community Workstream

Benefit-risk assessment is the cornerstone of decision making in medical care, playing a critical role in bringing treatments to market by informing decisions regarding drug development, licensing and reimbursement, and informing treatment decisions made by health care professionals and patients in clinical practice. In regulatory approval decision making, benefit and risk attributes are identified and defined based on available, aggregated clinical data from registration trials. In the context of major developments in recent years for involvement of patients as partners in all phases of drug development and in health care improvement, decision makers increasingly recognize the importance of informing treatment decisions by patient needs, values, experiences, and preferences. Using this as a basis, a DIA workstream was convened to explore the potential of individual-level benefit-risk assessment as a supplement to traditional group-level benefit-risk assessment for evaluating treatment. Various approaches as to how this information could be collected, including via patient-reported outcome measures, open-ended questioning, and stated-preference methods are presented. The utility of this information for various stakeholders is discussed.

Unique Challenges in Development, Psychometric Evaluation, and Interpretation of Daily and Event Diaries as Endpoints in Clinical Trials

By bringing data collection closer to real time and minimizing recall bias, patient diaries or event-driven logs offer substantial benefits over retrospective questionnaires for many patient-reported disease concepts. Such assessments are increasingly used to support primary and secondary endpoints in randomized controlled trials. These diaries have the potential to provide more reliable and valid assessment of patients’ subjective experiences of symptoms and disease events. However, use of such diaries presents significant and unique challenges depending on the context of use. Of note, while symptom-related label claims are those most frequently granted by regulatory authorities, no guidance specific to support the development, psychometric evaluation, and interpretation of endpoints derived from patient diaries exists. This article provides an overview of key methodological, statistical, and clinical considerations for implementation of patient diaries with a regulatory perspective in mind. Approaches and solutions covered in this article include (1) techniques to establish content validity based on obtaining qualitative insights in naturalistic settings and real-life experience of diary completion, (2) demonstration of psychometric properties with respect to day-to-day variability, and (3) aggregation of data from multiple days/events to move from items to endpoints. The importance of the patients’ engagement is highlighted in order to help overcome these challenges throughout all stages of diary and endpoint development and evaluation. This article can inform researchers who are developing or implementing patient diaries as clinical trial endpoints to ensure that the nuances of this mode of data collection are considered in the development of endpoints and prior to regulatory interactions.