Varying Willingness to Pay Based on Severity of Illness: Impact on Health Technology Assessment Outcomes of Inpatient and Outpatient Drug Therapies in The Netherlands.

OBJECTIVES: Since 2015, Zorginstituut Nederland (ZIN) has linked disease severity ranges of 0.10 to 0.40, 0.41 to 0.70, and 0.71 to 1.00 with willingness-to-pay (WTP) reference values of €20 000, €50 000, and €80 000 per quality-adjusted life year gained, respectively. We sought to review whether these changes have affected ZIN health technology assessment (HTA) outcomes for specialist and outpatient drugs. METHODS: ZIN recommendations for specialist and outpatient drugs published between January 1, 2012, and December 31, 2020, that included a pharmacoeconomic report were reviewed. Data were extracted on disease severity, proportional shortfall calculation, reported WTP reference value, outcomes related to the cost-effectiveness of the product, budget impact, and ZIN's recommendation including rationale for their advice. RESULTS: A total of 51 HTAs were included. Of the 20 HTAs published before June 2015, a total of 9 received positive recommendations, 7 were conditionally reimbursed, and 4 received negative recommendations. None reported WTP reference values. Of the 31 evaluations published after June 2015, a total of 4 products received positive recommendations, 1 was conditionally approved, and 26 received negative recommendations initially. Most products (65%) reported disease severity to be >0.70. CONCLUSIONS: Since 2015, most products have fallen within the highest category of disease severity. Although pre-2015 outcomes were varied, post-2015 products overwhelmingly received negative recommendations, and the proportion of products for which price negotiations were recommended has increased. These differences in outcomes may result from the introduction of an explicit WTP reference value, whether or not in combination with the severity-adjusted ranges, but may also reflect other national policy changes in 2015.

Choosing vs. allocating: discrete choice experiments and constant-sum paired comparisons for the elicitation of societal preferences.

BACKGROUND: There is growing evidence of a reluctance to allocate health care solely on the basis of maximizing quality-adjusted life years (QALYs). Stated preference methods can be used to elicit preferences for efficiency vs. equity in the allocation of health-care resources. OBJECTIVE: To compare discrete choice experiment (DCE) and constant-sum paired comparison (CSPC) methods for eliciting societal preferences. METHODS: Over a series of choice pairs, DCE respondents allocated a fixed budget to one preferred group and CSPC respondents allocated budget percentages between the groups. Questionnaires were compared in terms of completion rates, preference consistency, dominant preferences and derived attribute importance. RESULTS: There was no significant difference in the proportions that rated the questionnaires somewhat or extremely difficult, but a significantly greater proportion completed the DCE compared to the CSPC. Preference consistency was also higher in the DCE. The incidence of dominant preferences, including for aggregate QALYs, was low and not significantly different between questionnaires. Similarly, no CSCP respondents equalized budgets or outcomes in every task. Final health state was the most important attribute in both questionnaires, but the rankings diverged for the other attributes. Notably, the total patients' treated attribute was important in the CSPC but insignificant in the DCE, perhaps reflecting a 'prominence effect'. CONCLUSIONS: Despite lower completion rates and preference consistency, CSPC may offer advantages over DCE in eliciting preferences over the distribution of resources and/or outcomes as well as attribute levels, avoiding extreme 'all-or-nothing' distributions and possibly aligning respondent attention more closely with a societal perspective.

Adjusting survival time estimates to account for treatment switching in randomized controlled trials--an economic evaluation context: methods, limitations, and recommendations.

BACKGROUND: Treatment switching commonly occurs in clinical trials of novel interventions in the advanced or metastatic cancer setting. However, methods to adjust for switching have been used inconsistently and potentially inappropriately in health technology assessments (HTAs). OBJECTIVE: We present recommendations on the use of methods to adjust survival estimates in the presence of treatment switching in the context of economic evaluations. METHODS: We provide background on the treatment switching issue and summarize methods used to adjust for it in HTAs. We discuss the assumptions and limitations associated with adjustment methods and draw on results of a simulation study to make recommendations on their use. RESULTS: We demonstrate that methods used to adjust for treatment switching have important limitations and often produce bias in realistic scenarios. We present an analysis framework that aims to increase the probability that suitable adjustment methods can be identified on a case-by-case basis. We recommend that the characteristics of clinical trials, and the treatment switching mechanism observed within them, should be considered alongside the key assumptions of the adjustment methods. Key assumptions include the "no unmeasured confounders" assumption associated with the inverse probability of censoring weights (IPCW) method and the "common treatment effect" assumption associated with the rank preserving structural failure time model (RPSFTM). CONCLUSIONS: The limitations associated with switching adjustment methods such as the RPSFTM and IPCW mean that they are appropriate in different scenarios. In some scenarios, both methods may be prone to bias; "2-stage" methods should be considered, and intention-to-treat analyses may sometimes produce the least bias. The data requirements of adjustment methods also have important implications for clinical trialists.

Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis.

BACKGROUND: Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy. METHODS: A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity. RESULTS: Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69) for filgrastim, and 0.62 (95% CI: 0.44 to 0.88) for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62). In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim. FN incidence was significantly lower for pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to 0.98). CONCLUSIONS: Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim.

Cost-effectiveness of low-level heat wrap therapy for low back pain.

OBJECTIVES: To evaluate the cost-effectiveness and budget impact of a new heat wrap therapy for low back pain compared to paracetamol and ibuprofen from the perspective of the UK National Health Service (NHS). METHODS: We evaluated cost-effectiveness using data from a phase III trial comparing the three therapies in 371 patients aged 18 to 55 years presenting with acute uncomplicated low back pain. The primary effectiveness measure used was successful treatment, defined as both clinically meaningful pain relief and clinically meaningful reduction in disability. We conducted a simple evaluation using NHS prescription costs and a modeled extrapolation including the costs of further treatment and consultations for patients treated unsuccessfully or with adverse events. Uncertainty was addressed using nonparametric bootstrapping and sensitivity analyses. RESULTS: Successful treatment was reported by 57% of patients treated with heat wrap therapy, 26% treated with paracetamol and 18% treated with ibuprofen (P < 0.05 for heat wrap vs. both other groups). NHS prescription cost per patient was estimated to be 1.35 pounds Sterling for heat wrap therapy, 0.26 pounds Sterling for paracetamol, and 0.28 pounds Sterling for ibuprofen and cost per successful treatment was 3.52 pounds Sterling for heat wrap therapy compared to paracetamol, and 2.72 pounds Sterling compared to ibuprofen. In the modeled extrapolation, NHS cost per patient was 27.77 pounds Sterling for heat wrap therapy, 34.20 pounds Sterling for paracetamol, and 36.04 pounds Sterling for ibuprofen. Sensitivity analyses indicated that the findings were robust to plausible changes in data and assumptions. CONCLUSIONS: Economic evaluation of this study suggests that the NHS cost of introducing heat wrap therapy in place of oral analgesics would be modest and heat wrap therapy might potentially reduce the total cost of managing episodes of lower back pain.

Tratamiento del síndrome de intestino irritable: revisión de estudios aleatorizados controlados / Bowel Syndrome Treatment irritable: review of studies randomized controlled

Es bajo el porcentaje de estudios aleatorizados controlados sobre la eficacia de las terapias del síndrome de intestino irritable que cumplen con los criterios de calidad.

Health-related quality of life and cost impact of irritable bowel syndrome in a UK primary care setting.

OBJECTIVES: To identify the impact of irritable bowel syndrome (IBS) on health-related quality of life (HR-QOL), time off work and the utilisation and cost of health services. DESIGN: A case-control study was undertaken matching patients with IBS and controls. Quality-of-life information was collected using the Medical Outcomes Study 36-item Short Form (SF-36) health survey, EuroQOL instrument (EQ-5D) and IBS Quality-of-Life (IBS-QOL) instruments. Data on time off work was also collected. National Health Service (NHS) resource use in primary and secondary care was estimated by review of general practitioner (GP) and hospital records over a 12-month period. SETTING: Recruitment was from six GPs' surgeries in the Trent Region of the United Kingdom. PARTICIPANTS: 161 patients with IBS, as defined by the Rome Criteria I were recruited. These were compared with 213 controls matched for age, sex and social characteristics. MAIN OUTCOME MEASURES: SF-36 and EQ-5D scores; mean number of days off work; mean NHS costs per person during the 12-month study period. RESULTS: Patients with IBS had considerably lower HR-QOL than controls. They scored worse in all dimensions of the SF-36 and the EQ-5D and they had more time off work. On average patients with IBS cost the NHS 123 UK pounds (95% confidence interval: 35 UK pounds to 221 UK pounds, 1999 values) more per year than individuals in the control group (p = 0.04). CONCLUSIONS: IBS affects patients through reduced quality of life, more time off work and greater healthcare utilisation than a control group of patients without IBS. The difference in quality of life was pronounced and unusual in that it was influential in every dimension of both the SF-36 and the EQ-5D.