Linda Abetz-Webb

Interviewing to develop Patient-Reported Outcome (PRO) measures for clinical research: eliciting patients’ experience

Patient-reported outcome (PRO) measures must provide evidence that their development followed a rigorous process for ensuring their content validity. To this end, the collection of data is performed through qualitative interviews that allow for the elicitation of in-depth spontaneous reports of the patients’ experiences with their condition and/or its treatment. This paper provides a review of qualitative research applied to PRO measure development. A clear definition of what is a qualitative research interview is given as well as information about the form and content of qualitative interviews required for developing PRO measures. Particular attention is paid to the description of interviewing approaches (e.g., semi-structured and in-depth interviews, individual vs. focus group interviews). Information about how to get prepared for a qualitative interview is provided with the description of how to develop discussion guides for exploratory or cognitive interviews. Interviewing patients to obtain knowledge regarding their illness experience requires interpersonal and communication skills to facilitate patients’ expression. Those skills are described in details, as well as the skills needed to facilitate focus groups and to interview children, adolescents and the elderly. Special attention is also given to quality assurance and interview training. The paper ends on ethical considerations since interviewing for the development of PROs is performed in a context of illness and vulnerability. Therefore, it is all the more important that, in addition to soliciting informed consent, respectful interactions be ensured throughout the interview process.

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.

“Not Just Little Adults”: Qualitative Methods to Support the Development of Pediatric Patient-Reported Outcomes

The US FDA and the European Medicines Agency (EMA) have issued incentives and laws mandating clinical research in pediatrics. While guidances for the development and validation of patient-reported outcomes (PROs) or health-related quality of life (HRQL) measures have been issued by these agencies, little attention has focused on pediatric PRO development methods. With reference to the literature, this article provides an overview of specific considerations that should be made with regard to the development of pediatric PRO measures, with a focus on performing qualitative research to ensure content validity. Throughout the questionnaire development process it is critical to use developmentally appropriate language and techniques to ensure outcomes have content validity, and will be reliable and valid within narrow age bands (0–2, 3–5, 6–8, 9–11, 12–14, 15–17 years). For qualitative research, sample sizes within those age bands must be adequate to demonstrate saturation while taking into account children’s rapid growth and development. Interview methods, interview guides, and length of interview must all take developmental stage into account. Drawings, play-doh, or props can be used to engage the child. Care needs to be taken during cognitive debriefing, where repeated questioning can lead a child to change their answers, due to thinking their answer is incorrect. For the PROs themselves, the greatest challenge is in measuring outcomes in children aged 5–8 years. In this age range, while self-report is generally more valid, parent reports of observable behaviors are generally more reliable. As such, ‘team completion’ or a parent-administered child report is often the best option for children aged 5–8 years. For infants and very young children (aged 0–4 years), patient rating of observable behaviors is necessary, and, for adolescents and children aged 9 years and older, self-reported outcomes are generally valid and reliable. In conclusion, the development of PRO measures for use in children requires careful tailoring of qualitative methods, and performing research within narrow age bands. The best reporter should be carefully considered dependent on the child’s age, developmental ability, and the concept being measured, and team completion should be considered alongside self-completion and observer measures.

A review of the social, psychological, and economic burdens experienced by people with spina bifida and their caregivers.

IntroductionDespite measures to reduce the incidence of neural tube defects (NTDs), the rate of decline has not been as dramatic as expected. At least 300,000 newborns worldwide are known to be affected by NTDs each year. This comprehensive literature review summarizes the human and economic burden of NTDs to patients and caregivers, with particular focus on spina bifida (SB).MethodsPubMed, PsycINFO, and Embase were searched for studies from January 1976 to November 2010 that included clinical terms, such as NTD, and at least one patient-reported outcome or cost term. A conceptual model was also developed.ResultsAreas of peoples’ lives affected by SB included physical and role functioning, activities of daily living, bodily pain, vitality, emotional functioning, mental health, self-esteem, self-image, social functioning, relationships, and sexual functioning. Areas of caregivers’ lives affected included activities of daily living, work impact, time consumption, parental responsibilities (including responsibilities to other children), confidence, feelings and emotions, mental health, stress, social impact, psychological adjustment, relationships (with SB child, siblings, other family members), social support, coping strategies, and termination decisions. Cost burdens on patients and caregivers also include out-of-pocket costs, lost wages, or household production due to increased morbidity and mortality, transportation and other nonmedical costs.ConclusionsThis review highlights the need to provide care and support to individuals with SB and their caregivers. Results also emphasize the importance of effective long-term public health campaigns and/or newer strategies to prevent NTDs, such as SB.

Development and content validity testing of a patient-reported outcomes questionnaire for the assessment of hereditary angioedema in observational studies

BackgroundHereditary Angioedema (HAE), a rare genetic disease, manifests as intermittent, painful attacks of angioedema. Attacks vary in frequency and severity and include skin, abdominal and life-threatening laryngeal swellings. This study aimed to develop a patient reported outcome (PRO) tool for the assessment of HAE attacks, including their management and impact on patients’ lives, for use in clinical studies, or by physicians in general practice.MethodsThe results of open-ended face to face concept elicitation interviews with HAE patients in Argentina (n = 10) and the US (n = 33) were used to develop the first draft questionnaire of the HAE patient reported outcomes questionnaire (HAE PRO). Subsequently, in-depth cognitive debriefing interviews were performed with HAE patients in the UK (n = 10), Brazil (n = 10), Germany (n = 11) and France (n = 12). Following input from eight multinational clinical experts further cognitive interviews were conducted in the US (n = 12) and Germany (n = 12). Patients who experienced abdominal, cutaneous or laryngeal attacks of varying severity levels were included in all rounds of interviews. Across the rounds of interviews patients discussed their HAE attack symptoms, impacts and treatments. Cognitive debriefing interviews explored patient understanding and relevance of questionnaire items. All interviews were conducted face to face following a pre-defined semi-structured interview guide in the patient’s native language.ResultsPatients reported a variety of HAE symptoms, attack triggers, warning signs, attack impacts and treatment options which were used to develop the HAE PRO. The HAE PRO was revised and refined following input from patients and clinical experts. The final 18-item HAE PRO provides an assessment of the HAE attack experience including symptoms, impacts, treatment requirements, healthcare resource use and loss of productivity caused by HAE attacks.ConclusionsPatient and expert input has contributed to the development of a content valid questionnaire that assesses concepts important to HAE patients globally. HAE patients across cultures consider the HAE PRO a relevant and appropriate assessment of HAE attacks and treatment.

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.

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.

Measuring the Symptoms of Pediatric Constipation and Irritable Bowel Syndrome with Constipation: Expert Commentary and Literature Review

BackgroundSymptom measurement in pediatric chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) trials requires appropriately developed clinical outcome assessments (COAs).MethodsLiterature was reviewed to identify symptom COAs meeting regulatory standards. Searches were conducted in Pubmed/Medline, EMBASE, and PsychINFO. Title/abstracts were reviewed to identify qualitative studies and those using COAs to measure pediatric CIC/IBS symptoms. Pediatric functional gastrointestinal experts provided input on relevant symptom-concepts to measure.ResultsReview of 1,105 abstracts identified 1 relevant qualitative article and 113 articles including COAs. Symptoms most frequently measured in CIC studies were frequency of bowel movements, fecal incontinence/encopresis, abdominal pain, stool consistency, and painful defecation. Symptoms most frequently measured in IBS were abdominal pain, abdominal distention/bloating, stool consistency, frequency of bowel movements, and gas. Evidence of development/validity of COAs was limited. Expert feedback was broadly consistent with the literature.ConclusionFindings demonstrate consistency in the literature on key CIC/IBS symptoms to measure in pediatric trials, but existing COAs do not meet regulatory standards.

Listening to children’s and parents’ voices: using patient reported outcomes to empower patients with orphan diseases and their parents

Background Systematic evaluation of outcomes is essential for clinical trial research, yet outcomes often neglect the voice of the child and parent, particularly within paediatric orphan diseases. While guidance for the development and validation of Patient Reported Outcomes (PROs) and Observer Reported Outcomes (ObsRO) measures are available from EMA and FDA , little attention has focused on paediatric and orphan disease PRO/ObsRO development methods [1,2].