Cicely Kerr

Assessing and demonstrating data saturation in qualitative inquiry supporting patient-reported outcomes research.

In the patient-reported outcomes (PROs) field, strict regulatory requirements must be met for qualitative research that contributes to labeling claims for medicinal products. These requirements not only emphasize the importance of reaching saturation but also of providing documentary evidence that saturation has been reached. This paper reviews qualitative literature for useful definitions of the concept and for practical approaches for assessing saturation. The paper considers approaches in light of the rigorous regulatory requirements for PRO research that are used to support labeling claims for medicinal products and the wider requirements for flexibility and creativity in qualitative research in general. This assessment is facilitated by the use of examples from our past qualitative PRO studies. Based on conclusions from this assessment, we offer preliminary recommendations for future qualitative PRO studies for assessing and documenting saturation.

A Qualitative Investigation of Patients’ and Caregivers’ Experiences of Severe Sepsis*

Objectives:To explore and describe the subjective experiences and long-term impact of severe sepsis on survivors of severe sepsis and their informal caregivers (e.g., spouse or family member) through qualitative research methods. Design:A qualitative exploratory study using semi-structured interviews with survivors of severe sepsis and their informal caregivers in the United Kingdom and United States. Participants also completed a demographic background form and sites provided medical history details. Transcripts were analyzed using a thematic analysis approach. Setting:Patients were recruited from a large National Health Service hospital in the United Kingdom and a level 1 trauma center hospital in the United States. Caregivers were recruited through eligible patients. Interviews were conducted either face to face in participant’s homes or another convenient location or over the telephone. Patients:Patients who were 18 years old or older and had experienced an episode of severe sepsis in the previous 12 months were recruited by clinical staff in each hospital. Caregivers were family members or friends who had provided informal care for the patient after their episode of severe sepsis. Interventions:None. Measurements and Main Results:Thirty-nine interviews were conducted with 22 patients and 17 informal caregivers (of these 28 were conducted face-to-face and 11 by telephone). Five main themes were identified in the qualitative analysis: awareness and knowledge of severe sepsis; experience of hospitalization, ongoing impact of severe sepsis; impact on caregivers; and support after severe sepsis. Experiences varied depending on the patients’ health prior to the severe sepsis, with the worst affected reporting lasting impacts on multiple aspects of their life. Conclusions:The study extends what was understood about severe sepsis from the patients’ and caregivers’ perspectives from the previous limited literature. Caregivers as well as patients reported enduring impact. The study also identified problems of lack of awareness of diagnosis and understanding of severe sepsis by patients and caregivers and difficulties accessing appropriate healthcare providers and ancillary services after discharge from hospital.

A qualitative evaluation of the validity of published health utilities and generic health utility measures for capturing health-related quality of life (HRQL) impact of differentiated thyroid cancer (DTC) at different treatment phases

PurposeThis study explored the impact of differentiated thyroid cancer (DTC) on health-related quality of life (HRQL) at different treatment phases and evaluated the validity of published DTC utilities and generic health utility measures (EQ-5D and SF-6D) for economic evaluation of treatments for radio-iodine (RAI) refractory DTC.MethodsFocus groups and interviews were conducted with DTC patients grouped by treatment phase. Qualitative thematic analysis was conducted on interview/focus group transcripts. A thematic coding framework was developed to compare experiences between treatment phases and inform development of a conceptual model. Model concepts were mapped to EQ-5D and SF-6D domains/items.ResultsEight focus groups and 11 individual interviews were conducted with 52 DTC patients. Fifty symptoms and HRQL concepts were identified. The impact of DTC and DTC treatment on emotional and cognitive functioning was reported across the treatment phases. The impact on daily activities, mobility, and energy levels was greatest for patients with recurring/persistent or RAI-refractory DTC. Of the 50 concepts, 25 and 27 mapped directly onto domains/items in the EQ-5D and SF-6D, respectively. The SF-6D covered a broader range of DTC impact on emotional/physical problems and daily/social activities than did the EQ-5D.ConclusionsThe conceptual model summarizes the wide-ranging impact of DTC and its treatment on patients’ HRQL, particularly for those with recurring/persistent or RAI-refractory DTC. Findings suggest that published DTC utilities lack validity for RAI-refractory DTC and that the SF-6D may be more sensitive to HRQL impact of DTC than the EQ-5D.

Patient Reported Outcome (PRO) assessment in epilepsy: a review of epilepsy-specific PROs according to the Food and Drug Administration (FDA) regulatory requirements

Despite collection of patient reported outcome (PRO) data in clinical trials of antiepileptic drugs (AEDs), PRO results are not being routinely reported on European Medicines Agency (EMA) and Food and Drug Administration (FDA) product labels. This review aimed to evaluate epilepsy-specific PRO instruments against FDA regulatory standards for supporting label claims. Structured literature searches were conducted in Embase and Medline databases to identify epilepsy-specific PRO instruments. Only instruments that could potentially be impacted by pharmacological treatment, were completed by adults and had evidence of some validation work were selected for review. A total of 26 PROs were reviewed based on criteria developed from the FDA regulatory standards. The ability to meet these criteria was classified as either full, partial or no evidence, whereby partial reflected some evidence but not enough to comprehensively address the FDA regulatory standards. Most instruments provided partial evidence of content validity. Input from clinicians and literature was common although few involved patients in both item generation and cognitive debriefing. Construct validity was predominantly compromised by no evidence of a-priori hypotheses of expected relationships. Evidence for test-retest reliability and internal consistency was available for most PROs although few included complete results regarding all subscales and some failed to reach recommended thresholds. The ability to detect change and interpretation of change were not investigated in most instruments and no PROs had published evidence of a conceptual framework. The study concludes that none of the 26 have the full evidence required by the FDA to support a label claim, and all require further research to support their use as an endpoint. The Subjective Handicap of Epilepsy (SHE) and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) have the fewest gaps that would need to be addressed through additional research prior to any FDA regulatory submission, although the NDDI-E was designed as a screening tool and is therefore unlikely to be suitable as an instrument for capturing change in a clinical trial and the SHE lacks the conceptual focus on signs and symptoms favoured by the FDA.

Health-Related Quality of Life and Health Utilities in Metastatic Castrate-Resistant Prostate Cancer: A Survey Capturing Experiences from a Diverse Sample of UK Patients

BACKGROUNDnThe collection of preference-based health outcomes data (or utility values) is required to support cost-effectiveness analyses.nnnOBJECTIVEnThis study aimed to collect health-related quality of life (HRQOL) data in men with metastatic castration-resistant prostate cancer (CRPC) stratified by disease states.nnnMETHODSnMen with metastatic CRPC were recruited via UK patient associations, patient panels, and specialist recruiters and classified into four subgroups reflecting disease state: asymptomatic/mildly symptomatic before chemotherapy, symptomatic before chemotherapy, receiving chemotherapy, and postchemotherapy. HRQOL data (including five-level EuroQol five-dimensional questionnaire [EQ-5D-5L], European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC QLQ-C30], and 25-item prostate cancer-specific questionnaire module designed to supplement the EORTC QLQ-C30) along with background and medical history data were collected via an online survey. The EQ-5D-5L and the EORTC-8D (EORTC-8D is an 8 dimensional utility index scored from QLQ-C30 data) were both used to estimate utilities.nnnRESULTSnData were collected from a total sample of 163 men with metastatic CRPC. Utility values elicited by the EQ-5D-5L ranged from 0.830 for the asymptomatic/mildly symptomatic before chemotherapy disease state (95% confidence interval [CI] 0.795-0.865) to 0.625 for the symptomatic before chemotherapy disease state (95% CI 0.577-0.673). EORTC-8D utilities ranged from 0.856 (95% CI 0.831-0.882) to 0.697 (95% CI 0.664-0.731) for the same disease/treatment states.nnnCONCLUSIONSnThis online survey was designed to capture real-world HRQOL data describing men with CRPC. The study estimated utilities using two alternative methods, and the results show good agreement, suggesting that they are robust. This methodology offers a potentially higher quality alternative to vignette-based methods that are commonly used in oncology submissions.

Developing a utility index for the Aberrant Behavior Checklist (ABC-C) for fragile X syndrome

PurposeThis study aimed to develop a utility index (the ABC-UI) from the Aberrant Behavior Checklist-Community (ABC-C), for use in quantifying the benefit of emerging treatments for fragile X syndrome (FXS).MethodsThe ABC-C is a proxy-completed assessment of behaviour and is a widely used measure in FXS. A subset of ABC-C items across seven dimensions was identified to include in health state descriptions. This item reduction process was based on item performance, factor analysis and Rasch analysis performed on an observational study dataset, and consultation with five clinical experts and a methodological expert. Dimensions were combined into health states using an orthogonal design and valued using time trade-off (TTO), with lead-time TTO methods used where TTO indicated a state valued as worse than dead. Preference weights were estimated using mean, individual level, ordinary least squares and random-effects maximum likelihood estimation [RE (MLE)] regression models.ResultsA representative sample of the UK general public (nxa0=xa0349; mean age 35.8xa0years, 58.2xa0% female) each valued 12 health states. Mean observed values ranged from 0.92 to 0.16 for best to worst health states. The RE (MLE) model performed best based on number of significant coefficients and mean absolute error of 0.018. Mean utilities predicted by the model covered a similar range to that observed.ConclusionsThe ABC-UI estimates a wide range of utilities from patient-level FXS ABC-C data, allowing estimation of FXS health-related quality of life impact for economic evaluation from an established FXS clinical trial instrument.

Economic evaluation in short bowel syndrome (SBS): an algorithm to estimate utility scores for a patient-reported SBS-specific quality of life scale (SBS-QoL™)

PurposeCondition-specific preference-based measures can offer utility data where they would not otherwise be available or where generic measures may lack sensitivity, although they lack comparability across conditions. This study aimed to develop an algorithm for estimating utilities from the short bowel syndrome health-related quality of life scale (SBS-QoL™).MethodsSBS-QoL™ items were selected based on factor and item performance analysis of a European SBS-QoL™ dataset and consultation with 3 SBS clinical experts. Six-dimension health states were developed using 8 SBS-QoL™ items (2 dimensions combined 2 SBS-QoL™ items). SBS health states were valued by a UK general population sample (Nxa0=xa0250) using the lead-time time trade-off method. Preference weights or ‘utility decrements’ for each severity level of each dimension were estimated by regression models and used to develop the scoring algorithm.ResultsMean utilities for the SBS health states ranged from −0.46 (worst health state, very much affected on all dimensions) to 0.92 (best health state, not at all affected on all dimensions). The random effects model with maximum likelihood estimation regression had the best predictive ability and lowest root mean squared error and mean absolute error, and was used to develop the scoring algorithm.ConclusionsThe preference-weighted scoring algorithm for the SBS-QoL™ developed is able to estimate a wide range of utility values from patient-level SBS-QoL™ data. This allows estimation of SBS HRQL impact for the purpose of economic evaluation of SBS treatment benefits.

The importance of physical function to people with osteoporosis

SummaryThere is increasing need to understand patient outcomes in osteoporosis. This article discusses that fracture in osteoporosis can lead to a cycle of impairment, driven by complex psychosocial factors, having a profound impact on physical function/activity which accumulates over time. More information is required on how treatments impact physical function.IntroductionThere is increasing need to understand patient-centred outcomes in osteoporosis (OP) clinical research and management. This multi-method paper provides insight on the effect of OP on patients’ physical function and everyday activity.MethodsData were collected from three sources: (1) targeted literature review on OP and physical function, conducted in MEDLINE, Embase and PsycINFO; (2) secondary thematic analysis of transcripts from patient interviews, conducted to develop a patient-reported outcome instrument. Transcripts were re-coded to focus on OP impact on daily activities and physical function for those with and without fracture history; and (3) discussions of the literature review and secondary qualitative analysis results with three clinical experts to review and interpret the importance and implications of the findings.ResultsResults suggest that OP, particularly with fracture, can have profound impacts on physical function/activity. These impacts accumulate over time through a cycle of impairment, as fracture leads to longer term detriments in physical function, including loss of muscle, activity avoidance and reduced physical capacity, which in turn leads to greater risk of fracture and potential for further physical restrictions. The cycle of impairment is complex, as other physical, psychosocial and treatment-related factors, such as comorbidities, fears and beliefs about physical activity and fracture risk influence physical function and everyday activity.ConclusionMore information on how treatments impact physical function would benefit healthcare professionals and persons with OP in making treatment decisions and improving treatment compliance/persistence, as these impacts may be more salient to patients than fracture incidence.

Interpreting change from patient reported outcome (PRO) endpoints: patient global ratings of concept versus patient global ratings of change, a case study among osteoporosis patients

BackgroundRegulatory guidance recommends anchor-based methods for interpretation of treatment effects measured by PRO endpoints. Methodological pros and cons of patient global ratings of change vs. patient global ratings of concept have been discussed but empirical evidence in support of either approach is lacking. This study evaluated the performance of patient global ratings of change and patient global ratings of concept for interpreting patient stability and patient improvement.MethodsPatient global ratings of change and patient global ratings of concept were included in a psychometric validation study of an osteoporosis-targeted PRO instrument (the OPAQ-PF) to assess its ability to detect change and to derive responder definitions. 144 female osteoporosis patients with (n = 37) or without (n = 107) a recent (within 6 weeks) fragility fracture completed the OPAQ-PF and global items at baseline, 2 weeks (no recent fracture), and 12 weeks (recent fracture) post-baseline.ResultsResults differed between the two methods. Recent fracture patients reported more improvement while patients without recent fracture reported more stability on ratings of change than ratings of concept. However, correlations with OPAQ-PF score change were stronger for ratings of concept than ratings of change (both groups). Effect sizes for OPAQ-PF score change increased consistently with level of change in ratings of concept but inconsistently with ratings of change, with the mean AUC for prediction of a one-point change being 0.72 vs. 0.56.ConclusionsThis study provides initial empirical support for methodological and regulatory recommendations to use patient global ratings of concept rather than ratings of change when interpreting change captured by PRO instruments in studies evaluating treatment effects. These findings warrant being confirmed in a purpose-designed larger scale analysis.

Health state utility valuation in radioactive iodine-refractory differentiated thyroid cancer.

Purpose The aim of this study was to elicit utilities for radioactive iodine-refractory differentiated thyroid cancer (RR-DTC) and evaluate the impact of treatment response and toxicities on quality of life. Patients and methods RR-DTC health states were developed based on data from a previous qualitative study and iterative review by clinical experts. Following piloting, health states underwent valuation by 100 members of the UK public during time trade-off interviews. Mean utilities and descriptive distribution statistics were calculated, and a logistic regression analysis was conducted. Results The demographic characteristics of the study sample were generally reflective of the UK population. Clear differentiation in valuation between health states was observed. No response/stable disease had an adjusted utility value of 0.87, with a corresponding gain of +0.04 following a treatment response and a decline of −0.35 for disease progression. Adverse events were associated with utility decrements between −0.47 (grade III diarrhea) and −0.05 (grade I/II alopecia). Conclusion The trade-off interviews derived utility weights show clear differentiation between RR-DTC health states in response to treatment. The values reported in this study are suitable for cost-effectiveness evaluations for new treatments in RR-DTC.