Calibration of Quality-Adjusted Life Years for Oncology Clinical Trials

ContextQuality-adjusted life year (QALY) estimation is a well-known but little used technique to compare survival adjusted for complications. Lack of calibration and interpretation guidance hinders implementation of QALY analyses.ObjectivesWe conducted simulation studies to assess the impact of differences in survival, toxicity rates, and utility values on QALY results.MethodsSurvival comparisons used both log-rank and Wilcoxon testing. We examined power considerations for a North Central Cancer Treatment Group Phase III lung cancer clinical trial (89-20-52).ResultsSample sizes of 100 events per treatment have low power to generate a statistically significant difference in QALYs unless the toxicity rate is 44% higher in one arm. For sample sizes of 200 per arm and equal survival times, toxicity needs to be at least 38% more in one arm for the result to be statistically significant, using a utility of 0.3 for days with toxicity. Sample sizes of 300 (500)/arm provide 80% power if there is a 31% (25%) toxicity difference. If the overall survival hazard ratio between the two treatment arms is 1.25, then samples of at least 150 patients and 13% increased toxicity are necessary to have 80% power to detect QALY differences. In study 89-20-52, there was only 56% power to determine the statistical significance of the observed QALY differences, clarifying the enigmatic conclusion of no statistically significant difference in QALY despite an observed 14.5% increase in toxicity between treatments.ConclusionThis calibration allows researchers to interpret the clinical significance of QALY analyses and facilitates QALY inclusion in clinical trials through improved study design.     

Formulation and optimization of potassium iodide tablets

The use of potassium iodide (KI) as a protective agent against accidental radioactive exposure is well established. In this study, we aimed to prepare a KI tablet formulation using a direct compression method. We utilized Design of Experiment (DoE)/mixture design to define the best formulation with predetermined physical qualities as to its dissolution, hardness, assay, disintegration, and angle of repose. Based on the results from the DoE, the formulation had the following components (%w/w): Avicel 48.70%, silicon dioxide 0.27%, stearic acid (1.00%), magnesium stearate 2.45%, and dicalcium phosphate 18.69%, in addition to potassium iodide 28.89% (130 mg/tablet). This formulation was scaled-up using two tablet presses, a single-punch press and a rotary mini tablet press. The final scaled-up formulation was subjected to a variety of quality control tests, including photo-stability testing. The results indicate that potassium iodide tablets prepared by a rotary mini tablet press had good pharmaceutical characteristics and a shelf-life of 25 days when stored at room temperature protected from light.     

Use of [177Lu]Lu-DOTA-TATE in the treatment of gastroenteropancreatic neuroendocrine tumours: Results of a UK cost-effectiveness modelling study

AimTo evaluate the cost-effectiveness of [¹⁷⁷Lu]Lu-DOTA-TATE versus relevant comparators for the treatment of neuroendocrine tumours located in the gastrointestinal tract (GI-NETs) and the pancreas (P-NETs).Materials and methodsA three-state partitioned survival model was developed to perform a cost-utility analysis of [¹⁷⁷Lu]Lu-DOTA-TATE versus standard of care (high dose Octreotide LAR), everolimus and sunitinib. Effectiveness data for SoC, everolimus and sunitinib were obtained from published Kaplan–Meier survival curves. Given a lack of head-to-head effectiveness data, matching adjusted indirect comparisons (MAICs) were performed to population-adjust [¹⁷⁷Lu]Lu-DOTA-TATE survival data based on prognostic factors and derive estimates of relative effectiveness. Health state utilities were estimated from real-world evidence. Drug acquisition costs were taken from nationally published sources (BNF, NICE), and administration costs were based on treatment protocols in [¹⁷⁷Lu]Lu-DOTA-TATE studies, combined with nationally published unit costs (PSSRU, DoH reference costs). Incidence of adverse events were estimated using published sources. A discount rate of 3.5% was applied to both utilities and costs, and deterministic and probabilistic sensitivity analyses were performed. Costs were included from an NHS perspective and presented in 2017/18 GBP (and PPP Euros for base case).ResultsIn GI-NETs, the incremental cost-effectiveness ratio (ICER) of [¹⁷⁷Lu]Lu-DOTA-TATE compared to SoC and everolimus was £26,528 (€27,672) and £24,145 (€25,186) per QALY, respectively. In P-NETs, the ICER of [¹⁷⁷Lu]Lu-DOTA-TATE compared to SoC was £22,146 (€23,101) or £28,038 (€29,251) dependent on matched population, and £21,827 (€22,766) and £15,768 (€16,445) compared to everolimus and sunitinib, respectively.ConclusionsAt a willingness to pay threshold of £30,000, [¹⁷⁷Lu]Lu-DOTA-TATE is likely to be a cost-effective treatment option for GI-NET and P-NET patients versus relevant treatment comparators (NHS perspective).     

Cost-effectiveness of maternal immunization against neonatal invasive Group B Streptococcus in the Netherlands

BackgroundNeonatal invasive Group B Streptococcus (GBS) infection causes considerable disease burden in the Netherlands. Intrapartum antibiotic prophylaxis (IAP) prevents early-onset disease (EOD), but has no effect on late-onset disease (LOD). A potential maternal GBS vaccine could prevent both EOD and LOD by conferring immunity in neonates.ObjectiveExplore under which circumstances maternal vaccination against GBS would be cost-effective as an addition to, or replacement for the current risk factor-based IAP prevention strategy in the Netherlands.MethodsWe assessed the maximum cost-effective price per dose of a trivalent (serotypes Ia, Ib, and III) and hexavalent (additional serotypes II, IV, and V) GBS vaccine in addition to, or as a replacement for IAP. To project the prevented costs and disease burden, a decision tree model was developed to reflect neonatal GBS disease and long-term health outcomes among a cohort based on 169,836 live births in the Netherlands in 2017.ResultsUnder base-case conditions, maternal immunization with a trivalent vaccine would gain 186 QALYs and prevent more than €3.1 million in health care costs when implemented in addition to IAP. Immunization implemented as a replacement for IAP would gain 88 QALYs compared to the current prevention strategy, prevent €1.5 million in health care costs, and avoid potentially ~ 30,000 IAP administrations. The base-case results correspond to a maximum price of €58 per dose (vaccine + administration costs; using a threshold of €20,000/QALY). Expanding the serotype coverage to a hexavalent vaccine would only have a limited additional impact on the cost-effectiveness in the Netherlands.ConclusionsA maternal GBS vaccine could be cost-effective when implemented in addition to the current risk factor-based IAP prevention strategy in the Netherlands. Discontinuation of IAP would save costs and prevent antibiotic use, however, is projected to lead to a lower health gain compared to vaccination in addition to IAP.     

非梗阻性无精子症患者的生育生活质量及影响因素调查

目的 了解非梗阻性无精子症患者的生育生活质量现状及其影响因素。 方法 选取生殖中心就诊的311例非梗阻性无精子症患者，采用一般情况问卷、简明中文版生育生活质量量表及社会支持评定量表进行横断面问卷调查。 结果 非梗阻性无精子症患者生育生活质量得分为（65.55±13.52）分。回归分析显示，不育年限、家庭年收入、接受辅助生殖技术治疗次数和社会支持为非梗阻性无精子症患者生育生活质量的影响因素，可解释总变异的35.4%。 结论 非梗阻性无精子症患者生育生活质量较低，医护人员应重点关注不育年限长、家庭收入低、接受辅助生殖技术治疗次数多及社会支持水平低者，采取针对性干预措施提高其生活质量。