The lived experience of major and treatment-resistant depression in England: a mixed-methods study.

INTRODUCTION: Major depressive disorder (MDD) is a common, frequently recurrent condition associated with decreased well-being and increased healthcare-related costs. Mixed-methods research provides multiple ways of illustrating the phenomenon to better understand patient experience, including where treatment is not working, referred to here as treatment-resistant depression (TRD). METHODS: A mixed-methods study investigated the experiences of people with symptomatic MDD, symptomatic TRD or TRD in remission, surveying 148 adults recruited from English clinical sites to measure symptom severity (Patient Health Questionnaire-9 [PHQ-9]), HRQoL (EQ-5D-5L/World Health Organisation Brief Assessment of QoL [WHOQOL-BREF]) and work productivity/activity impairment (WPAI:D). Interviews with 26 survey respondents were analysed thematically. Integrated datasets explored areas of convergence and divergence, with concepts mapped against the EQ-5D-5L. RESULTS: Qualitative data explained low WHOQOL-BREF domain scores and the interrelation of psychological, emotional, cognitive and physical difficulties. Tiredness, lack of energy and motivation impacted daily activities, socialising and career goals. Low work performance scores were explained by poor concentration, decision-making and motivation. Participants also described the influence of social support and housing insecurity. Only 19 % of HRQoL qualitative codes mapped to the EQ-5D-5L. Themes dominant in patients with TRD were inability to cope, self-care challenges, dissatisfaction with mental health services and treatment pessimism. LIMITATIONS: Limited data collected on people with TRD in remission. CONCLUSIONS: The EQ-5D-5L and WPAI:D likely underestimate how depression impacts the HRQoL and work of people with MDD or TRD. Qualitative data suggest increased distress for people with TRD compared to those with MDD. Clinical management and treatment access decisions should consider the broader impacts of depression and environmental factors affecting the patient's experience.

The impact of treatment-resistant depression on the lives of carers: A mixed-methods study.

INTRODUCTION: The lived experiences of informal carers of people with depression, particularly those with treatment-resistant depression (TRD), are rarely explored, despite their vital supportive role. METHODS: This mixed-methods study explored the quality of life (QoL) and experiences of carers of individuals with symptomatic TRD (Carers-Sym-TRD; n = 79) or in remission post-TRD (Carers-Rem-TRD; n = 20). Participating carers completed quantitative surveys measuring health-related and broader QoL (EQ-5D-5L/WHOQOL-BREF) and work productivity/activity impairment (WPAI:MM-CG). Interviews were also conducted with 12 Carers-Sym-TRD and 11 Carers-Rem-TRD and analysed thematically. RESULTS: Carers-Sym-TRD had impaired QoL compared with Carers-Rem-TRD, with significantly lower EQ-5D-5L index values (median = 0.84/1.00, respectively; p = 0.020) and WHOQOL-BREF overall score (median = 63.0/70.1; p < 0.001), physical health (median = 15.3/17.3; p < 0.001), psychological health (median = 13.3/14.7; p = 0.017), social relationships (median = 13.3/14.7; p = 0.017) and environment (median = 14.5/16.5; p = 0.011) domain scores. Work productivity/activity impairment was greatest in Carers-Sym-TRD across most WPAI:MM-CG domains, with a higher degree of impairment reported on the presenteeism and work productivity domains, however, there were no significant differences between the carer groups. Interview data suggested that impacts on carers' psychological/emotional wellbeing led to physical problems, which affected cognition and daily performance; Also, successful treatment for the person with depression helped carers worry less and reclaim their independence. LIMITATIONS: Recruitment challenges limited the Carers-Rem-TRD sample; clinical validation of the patient's depression diagnosis was not confirmed for all carers. CONCLUSIONS: TRD has an extensive adverse impact on carers' lives. Carers-Sym-TRD had significantly impaired QoL across a variety of domains compared with Carers-Rem-TRD, suggesting that achieving remission not only benefits patients but also those who care for them.

Health-related quality of life burden associated with treatment-resistant depression in UK patients: Quantitative results from a mixed-methods non-interventional study.

BACKGROUND: Major depressive disorder (MDD) and its more intractable variant, treatment-resistant depression (TRD), are common conditions that adversely affect patient well-being and health-related quality of life (HRQoL). This study aimed to quantify the impact of MDD and particularly TRD on the HRQoL, functioning and productivity of UK patients to support clinical and reimbursement decisions and policymaking. METHODS: 148 patients with clinician-verified symptomatic (non-treatment-resistant) MDD (Patients-MDD; n = 61) or TRD (Patients-TRD; n = 87) were recruited from ten clinical sites. Participants completed validated patient-reported outcome measures assessing depressive symptom severity (Patient Health Questionnaire-9 [PHQ-9]), HRQoL (EQ-5D-5 L/abbreviated World Health Organization Quality of Life Questionnaire [WHOQOL-BREF]) and work productivity/activity impairment (WPAI:D). RESULTS: Patients-TRD and Patients-MDD reported similar levels of depressive symptom severity (mean PHQ-9 16.2/16.6, respectively). However, HRQoL was significantly poorer for Patients-TRD compared with Patients-MDD, both in the overall cohort (median EQ-5D-5 L utility 0.606/0.721, respectively [p = 0.021]; WHOQOL-BREF overall score 55.2/58.8 [p = 0.024]) and in patients with a PHQ-9 score ≥15 (median EQ-5D-5 L utility 0.415/0.705, respectively [p<0.001]). Although a numerically lower proportion of Patients-TRD were employed (45% vs 57% of Patients-MDD; p = 0.204), employed Patients-MDD reported significantly higher absenteeism and work productivity loss. LIMITATIONS: A minority of patients screened as having symptomatic MDD or TRD self-reported low PHQ-9 symptom severity. This was addressed with a subgroup analysis of patients with more severe depression. CONCLUSIONS: TRD is associated with an added patient HRQoL burden, above that observed for non-treatment-resistant MDD. This highlights the unmet need for greater access to improved treatment, including new treatment options for Patients-TRD.

Current treatments used in clinical practice for major depressive disorder and treatment resistant depression in England: A retrospective database study.

BACKGROUND: Major depressive disorder (MDD) is a chronic recurrent or episodic psychiatric illness that can be successfully treated with oral antidepressants, yet one-in-three patients do not respond to currently-available treatments. According to the FDA and EMA, patients are considered to have treatment-resistant depression (TRD) when their MDD fails to respond adequately to ≥2 successive antidepressants in a single episode. AIMS: To describe current clinical management of patients with MDD and TRD in England, including treatment strategies and referral to secondary mental healthcare. METHOD: A retrospective cohort study of adult patients identified in primary care with diagnosed MDD, including a TRD subgroup (≥2 treatment failures as determined by treatment dynamics) was conducted using the Clinical Practice Research Datalink GOLD primary care database linked to Hospital Episode Statistics and Mental Health Services Data Set data (Protocol 19_019R). RESULTS: 41,375 patients with MDD (mean age 44yrs, 62% female, median follow-up 29mths); and 1,051 (3%) patients with TRD were identified. Mean time-to-TRD was 18 months. Most patients (>99%) received first-line antidepressant monotherapy. Following TRD criteria being met, antidepressant monotherapy use remained most frequent from TRD first-line (70%) to fifth-line (48%). Dual/triple antidepressant use remained constant (range:24%-26%), while augmented antidepressant use increased from TRD first-line (7%) to third-line (17%). Minimal non-pharmacological therapies were observed. CONCLUSIONS: Despite current clinical guidelines recommending a stepwise approach, many patients frequently cycle through numerous antidepressants with similar mechanisms of action and efficacy. These findings indicate a high unmet need for new treatments that improve outcomes in these patient populations.

Testing the validity and responsiveness of a new cancer-specific health utility measure (FACT-8D) in relapsed/refractory mantle cell lymphoma, and comparison to EQ-5D-5L.

BACKGROUND: The FACT-8D is a new cancer-specific, preference-based measure (PBM) of health, derived from the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire. The FACT-8D's measurement properties have not been tested to date. We assessed it's validity and responsiveness in relapsed/refractory mantle cell lymphoma (RR MCL) and compared the results to the EQ-5D-5L. METHODS: Blinded analysis of pooled data from a phase 3 clinical trial. FACT-8D baseline and follow-up data (weeks 4, 7, 16, 31) were scored using Australian preference weights, the first available value-set. Convergent validity was assessed by estimating baseline correlations with the FACT-Lym total score, Trial Outcome Index (TOI), FACT-Lym lymphoma-specific sub-scale (LymS), EQ-5D Visual Analog Scale (VAS), and haemoglobin (HgB). Relevant clinical variables were used to categorise patients to test known groups' validity and responsiveness was investigated using data from baseline (n = 250) and week 31 (n = 130). Results were compared with EQ-5D-5L, scored using the UK 3L crosswalk and the 5L England value-sets. RESULTS: The FACT-8D showed good convergent validity and responsiveness; baseline Pearson correlation coefficients between FACT-8D Index scores and other PRO measures were moderate to very strong (range: 0.49 for the EQ-VAS to 0.79 for FACT TOI) and the size of the change in FACT-8D Index scores at week 31 differed significantly (p < 0.005) between patients categorised as improved, worsened or stable using the FACT-Lym total score, LymS, and HgB. However, when assessing known groups' validity, FACT-8D failed to discriminate between patients categorised by health status on four of the seven variables analysed. Overall, FACT-8D and EQ-5D-5L performed similarly, although EQ-5D-5L showed better known groups' validity. CONCLUSIONS: This is the first investigation into the psychometric properties of the FACT-8D. In this RR MCL trial dataset, it showed good convergent validity and responsiveness, but poorer known groups' validity, and EQ-5D performed as well or better on the tests conducted. The FACT-8D may offer an alternative method to generate utilities for the cost-effectiveness analysis of cancer treatments but needs further testing in other types of cancer patients. Evaluation of utility gains may have been limited by high baseline performance status in this RR MCL trial sample.

Disutility Study for Adult Patients with Moderate to Severe Crohn's Disease.

BACKGROUND: Crohn's disease (CD) treatments and associated adverse events (AEs) can be burdensome for patients. However, specific values which quantify the impact on health-related quality of life (HRQL) for economic evaluation are lacking. OBJECTIVES: This study aimed to elicit health utility values for AEs related to biologic treatment and surgical complications for CD in the UK. METHODS: Health states were developed by literature review and interviews with CD patients (n=6) and gastroenterologists (n=3). Draft health states were validated in cognitive debrief interviews with patients (n=4) and gastroenterologists (n=2). Treatment AEs were described with moderate-severe CD (reference state) and included hypersensitivity, injection site reactions, serious infection, lymphoma, and tuberculosis. Surgical complications were described following bowel surgery (reference state) and included anastomotic leak, wound infection, prolonged ileus/bowel obstruction, and intra-abdominal abscess. Health states were valued by 100 members of the general public who completed background questions, EQ-5D-3L, visual analogue scale rating task and time trade-off (TTO) interviews. RESULTS: The mean TTO value for reference states 'moderate to severe CD' and 'bowel surgery' were 0.70 (SD=0.28) and 0.69 (SD=0.28). Participants rated lymphoma as the worst AE/surgical complication state (0.44, SD=0.37), followed by tuberculosis (0.47, SD=0.85) and anastomotic leak (0.48, SD=0.38). Values of other AE/surgical complication states ranged from 0.76 (hypersensitivity) to 0.56 (intra-abdominal abscess). CONCLUSIONS: This study provides utility estimates for AE and surgical complication health states not previously assessed in the context of CD. As new treatments are emerging, it is important to include these influences on quality of life in any economic evaluation of treatments.

Evaluating the Content Validity of Four Performance Outcome Measures in Patients with Elective Hip Replacements and Hip Fractures.

OBJECTIVES: To assess the content validity of performance outcome (PerfO) measures for use with patients undergoing hip fracture (HF) surgery and elective total hip replacement (eTHR). METHODS: This study was a substudy of a broader evaluation of measurement properties of PerfO measures. The PerfO measures assessed were timed up and go (TUG), four-step stair climb (4SC), long stair climb (LSC), and repeated chair stand (RCS). For this substudy, HF and eTHR participants were interviewed to evaluate the relevance and difficulty of each PerfO measure. Qualitative analysis was conducted on interview transcripts, and summaries of coded data were produced to assess saturation. RESULTS: All 18 HF participants related the PerfO measures (TUG, 4SC, and RSC) to activities they completed in daily life, with slight variations in some specific aspects. For the eight eTHR participants, the correspondence between the PerfO measures (TUG, 4SC, and LSC) and activities in daily life varied: all participants saw similarity in the movements for the TUG; most undertook short stair climbs in daily life, but most did not regularly undertake LSC in daily life. Nevertheless, all HF and eTHR participants reported that the PerfO measures were relevant and had a level of difficulty similar to daily activities. CONCLUSIONS: This study contributes novel methods that adapt US regulatory guidance for patient-reported outcome measures to the evaluation of PerfO measures. A structured approach was used to explore specific details of each measure and correspondence to everyday life. This study demonstrates how content validity of PerfO measures can be meaningfully assessed.

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.

BACKGROUND: Regulatory 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. METHODS: Patient 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. RESULTS: Results 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. CONCLUSIONS: This 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-related quality of life in Parkinson's: impact of 'off' time and stated treatment preferences.

PURPOSE: Long-term levodopa therapy and related fluctuating plasma concentrations are associated with between-dose periods of 'off time' resulting in substantial variation in symptoms and functioning throughout the day in people with Parkinson's (PwP). METHODS: PwP across UK, France, Spain and Italy completed an online survey to explore: the impact of 'off time' on (1) health-related quality of life (HRQL) and (2) on functioning and ability to undertake usual activities; (3) the value of 'off time' relative to other factors associated with Parkinson's through a stated preference discrete choice experiment (SPDCE). RESULTS: In total, 305 PwP completed the online survey. Overall mean HRQL (utility) score was significantly lower for 'off time' (0.37) than for 'on time' (0.60). All attributes within the SPDCE were significant predictors of treatment choice, although increased duration of 'on time' (per hour per day: odds ratio (OR) = 1.40) and predictability of 'off time' to within 30 min (OR = 1.42) were valued most highly. CONCLUSIONS: 'On time' and predictability of 'off time' are highly valued by PwP. Due to substantial diurnal variation of Parkinson's symptoms, standard patient-reported outcome (PRO) assessments may not adequately capture the impact of 'off time' on HRQL and participation in daily activities.

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.

BACKGROUND: The collection of preference-based health outcomes data (or utility values) is required to support cost-effectiveness analyses. OBJECTIVE: This study aimed to collect health-related quality of life (HRQOL) data in men with metastatic castration-resistant prostate cancer (CRPC) stratified by disease states. METHODS: Men 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. RESULTS: Data 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. CONCLUSIONS: This 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.

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.

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.

PURPOSE: This 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. METHODS: Focus 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. RESULTS: Eight 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. CONCLUSIONS: The 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.

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

PURPOSE: This 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). METHODS: The 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. RESULTS: A representative sample of the UK general public (n = 349; mean age 35.8 years, 58.2% 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. CONCLUSIONS: The 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™).

PURPOSE: Condition-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™). METHODS: SBS-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 (N = 250) 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. RESULTS: Mean 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. CONCLUSIONS: The 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.

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.

The potential of Web-based interventions for heart disease self-management: a mixed methods investigation.

BACKGROUND: Existing initiatives to support patient self-management of heart disease do not appear to be reaching patients most in need. Providing self-management programs over the Internet (web-based interventions) might help reduce health disparities by reaching a greater number of patients. However, it is unclear whether they can achieve this goal and whether their effectiveness might be limited by the digital divide. OBJECTIVE: To explore the effectiveness of a web-based intervention in decreasing inequalities in access to self-management support in patients with coronary heart disease (CHD). METHODS: Quantitative and qualitative methods were used to explore use made of a web-based intervention over a period of 9 months. Patients with CHD, with or without home Internet access or previous experience using the Internet, were recruited from primary care centers in diverse socioeconomic and ethnic areas of North London, UK. Patients without home Internet were supported in using the intervention at public Internet services. RESULTS: Only 10.6% of eligible patients chose to participate (N=168). Participants were predominantly Caucasian well-educated men, with greater proportions of male and younger CHD patients among participants than were registered at participating primary care practices. Most had been diagnosed with CHD a number of years prior to the study. Relatively few had been newly diagnosed or had experienced a cardiac event in the previous 5 years. Most had home Internet access and prior experience using the Internet. A greater use of the intervention was observed in older participants (for each 5-year age increase, OR 1.25 for no, low or high intervention use, 95% CI, 1.06-1.47) and in those that had home Internet access and prior Internet experience (OR 3.74, 95% CI, 1.52-9.22). Less use was observed in participants that had not recently experienced a cardiac event or diagnosis (≥ 5 years since cardiac event or diagnosis; OR 0.69, 95% CI, 0.50-0.95). Gender and level of education were not statistically related to level of use of the intervention. Data suggest that a recent cardiac event or diagnosis increased the need for information and advice in participants. However, participants that had been diagnosed several years ago showed little need for information and support. The inconvenience of public Internet access was a barrier for participants without home Internet access. The use of the intervention by participants with little or no Internet experience was limited by a lack of confidence with computers and discomfort with asking for assistance. It was also influenced by the level of participant need for information and by their perception of the intervention. CONCLUSIONS: The availability of a web-based intervention, with support for use at home or through public Internet services, did not result in a large number or all types of patients with CHD using the intervention for self-management support. The effectiveness of web-based interventions for patients with chronic diseases remains a significant challenge.

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 heartbeat moment': qualitative study of GP views of patients bringing health information from the internet to a consultation.

BACKGROUND: Government policy is to encourage self-help among patients. The internet is increasingly being used for health information. The literature on the role of the internet in the doctor-patient consultation remains sparse. AIM: To determine the perceived responses of GPs to internet-informed patients in consultations and the strategies GPs use for dealing with information from the internet being brought into consultations. DESIGN OF STUDY: A qualitative study design was used, with semi-structured interviews. SETTING: GPs based in North Central London. METHOD: Analysis was conducted by a multidisciplinary team of researchers. Participants were 11 GPs: five partners, three locums, and three salaried doctors; seven were white, three were Asian, and one was of Chinese origin. The median year of General Medical Council (GMC) registration was 1989. There were six women and five men; five participants worked in training practices. RESULTS: GPs experienced considerable anxiety in response to patients bringing information from the internet to a consultation but were able to resolve this anxiety. The study participants learned to distance themselves from their emotional response, and used cognitive and behavioural techniques to assist them in responding appropriately to patients. These techniques included buying time in a consultation, learning from previous consultations, and using the internet as an ally, by directing patients to particular websites. The importance for doctors of feeling valued by patients was apparent, as was the effect of the prior doctor-patient relationship. CONCLUSION: GPs interviewed used sophisticated mechanisms for dealing with their emotions. GPs struggling with internet-informed patients can use the mechanisms described to alleviate the difficulties.

Applying user-generated quality criteria to develop an Internet intervention for patients with heart disease.

Internet interventions can help people to self-manage chronic disease. However, they are only likely to be used if they meet patients' perceived needs. We have developed an Internet intervention in two stages to meet the needs of patients with coronary heart disease (CHD). First, user-generated criteria were applied to an existing US-based intervention called 'CHESS Living with Heart Disease' which provides information, emotional and social support, self-assessment and monitoring tools, and behavioural change support. This identified the development work required. Then we conducted a user evaluation with a panel of five patients with CHD. Overall, users generally made positive comments about the information content. However they were critical of presentation, ease of navigation through the content, understanding what was offered in the different services and finding the information they were after. Applying user-generated quality criteria proved useful in developing an intervention to meet the needs of UK patients with CHD.