Physicians’ Preferences for Bone Metastases Drug Therapy in the United States

AbstractObjectiveSeveral characteristics of bone-targeted agents are considered when making treatment decisions. This study evaluated physicians’ therapy preferences for preventing skeletal-related events (SREs) in patients with bone metastases secondary to solid tumors.MethodsA Web-enabled, discrete-choice experiment online survey was conducted among physicians who treated patients with bone metastases and solid tumors in the United States. Respondents chose between pairs of hypothetical medications defined by combinations of six attributes at varying levels for two hypothetical patients. Preference weights for attribute levels were estimated using a random-parameters logit model.ResultsIn total, 200 physicians completed the survey. Their mean age was 52 years, 57% were in practice for more than 15 years, 37% were oncologists, and 65% treated 10 or fewer patients with bone metastases weekly. Out-of-pocket cost to patients was the most important attribute overall. Among clinical outcomes, time to first SRE and risk of renal impairment were the most important attributes. Statistically significant preferences were observed for all attribute levels for time to first SRE, risk of renal impairment, and mode of administration. Predicted choice probability analysis showed that physicians preferred a hypothetical medication with attributes similar to those of denosumab over one with attributes similar to those of zoledronic acid.ConclusionsPhysicians indicated that clinical attributes are important when considering bone-targeting therapy for bone metastases, but consistent with the current health care landscape, patient out-of-pocket cost was the most important. With health care costs being increasingly shifted to patients, physicians require accurate information about co-pays and assistance programs to avoid patients receiving less costly, yet potentially inferior, treatment

Darolutamide and health-related quality of life in patients with non-metastatic castration-resistant prostate cancer : An analysis of the phase III ARAMIS trial

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.BACKGROUND: In the ARAMIS trial, darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT significantly improved metastasis-free survival (MFS), overall survival (OS) and time to pain progression in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Herein, we present analyses of patient-reported health-related quality of life (HRQoL) outcomes. PATIENTS AND METHODS: This double-blind, placebo-controlled, phase III trial randomised patients with nmCRPC and prostate-specific antigen doubling time ≤10 months to darolutamide 600 mg (n = 955) twice daily or matched placebo (n = 554) while continuing ADT. The primary end-point was MFS; the secondary end-points included OS and time to pain progression. In this analysis, HRQoL was assessed by the time to deterioration using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) prostate cancer subscale (PCS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (EORTC QLQ-PR25) subscales. RESULTS: Darolutamide significantly prolonged time to deterioration of FACT-P PCS versus placebo (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.70-0.91; P = 0.0005) at the primary analysis (cut-off date: 3rd September 2018). Time to deterioration of EORTC QLQ-PR25 outcomes showed statistically significant delays with darolutamide versus placebo for urinary (HR 0.64, 95% CI 0.54-0.76; P < 0.0001) and bowel (HR 0.78, 95% CI 0.66-0.92; P = 0.0027) symptoms. Time to worsening of hormonal treatment-related symptoms was similar between the two groups. CONCLUSION: In patients with nmCRPC who are generally asymptomatic, darolutamide maintained HRQoL by significantly delaying time to deterioration of prostate cancer-specific quality of life and disease-related symptoms versus placebo.publishersversionPeer reviewe

Efficacy and Safety of Darolutamide in Patients with Nonmetastatic Castration-resistant Prostate Cancer Stratified by Prostate-specific Antigen Doubling Time : Planned Subgroup Analysis of the Phase 3 ARAMIS Trial

Background: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo. However, patients remain at a high risk with a PSADT of >6 mo. Objective: To evaluate the efficacy and safety of darolutamide versus placebo in patients stratified by PSADT >6 or ≤6 mo. Design, setting, and participants: A planned subgroup analysis of a global multicenter, double-blind, randomized, phase 3 trial in men with nmCRPC and PSADT ≤10 mo was conducted. Intervention: Patients were randomized 2:1 to oral darolutamide 600 mg twice daily or placebo, while continuing androgen-deprivation therapy. Outcome measurements and statistical analysis: The primary endpoint was metastasis-free survival (MFS). Secondary endpoints were overall survival (OS) and times to pain progression, first cytotoxic chemotherapy, and symptomatic skeletal events. Quality of life (QoL) was measured using validated prostate-relevant tools. Safety was recorded throughout the study. Results and limitations: Of 1509 patients enrolled, 469 had PSADT >6 mo (darolutamide n = 286; placebo n = 183) and 1040 had PSADT ≤6 mo (darolutamide n = 669; placebo n = 371). Baseline characteristics were balanced between subgroups. Darolutamide significantly prolonged MFS versus placebo in both subgroups (unstratified hazard ratio [95% confidence interval]: PSADT >6 mo, 0.38 [0.26–0.55]; PSADT ≤6 mo, 0.41 [0.33–0.52]). OS and other efficacy and QoL endpoints favored darolutamide with significant improvement over placebo in both subgroups. The incidence of adverse events, including events commonly associated with androgen receptor inhibitors (fractures, falls, hypertension, and mental impairment), and discontinuations due to adverse events were low and similar to placebo. Limitations include small subgroup populations. Conclusions: In patients with nmCRPC and PSADT >6 mo (maximum 10 mo), darolutamide provided a favorable benefit/risk ratio, characterized by significant improvements in MFS, OS, and other clinically relevant endpoints; maintenance of QoL; and favorable tolerability. Patient summary: In patients with prostate cancer that has stopped responding to standard hormonal therapy (indicated by an increase in prostate-specific antigen [PSA] levels), there is a risk that the cancer will spread to other parts of the body. This risk is highest when the time it takes for the PSA level to double (ie, “PSA doubling time” [PSADT]) is less than 6 mo. However, there is still a risk that the cancer will spread even if the PSADT is longer than 6 mo. In a group of patients whose PSADT was more than 6 mo but no more than 10 mo, treatment with darolutamide slowed the cancer spread and allowed them to live longer than patients who received placebo (inactive drug). Darolutamide treatment did not cause many side effects and helped maintain patients’ quality of life without disruptions.publishedVersionPeer reviewe

Patient Benefit-Risk Tradeoffs for Radioactive Iodine-Refractory Differentiated Thyroid Cancer Treatments

Background. The aims of this study were to assess patients’ preferences to wait or start systemic treatment and understand how patients would make tradeoffs between certain severe adverse events (AEs) and additional months of progression-free survival (PFS). Materials and Methods. Adults in France, Germany, and Spain with a diagnosis of DTC and who have had at least one RAI treatment completed a direct-elicitation question and a discrete-choice experiment (DCE) online. The direct-elicitation question asked respondents whether they would opt out of treatment when their tumor is RAI-R. In the DCE, respondents chose between 12 pairs of hypothetical RAI-R DTC treatment profiles. Profiles were defined by magnitudes of efficacy (PFS) and safety (severe hand-foot skin reaction [HFSR], severe proteinuria, and severe hypertension). A main-effects random-parameters logit model was estimated. Results. 134 patients completed the survey. Most patients (86.6%) opted for treatment rather than “wait and see” decision. Patients placed a greater weight on the risk of severe hypertension than the risk of proteinuria and HFSR. Conclusions. DTC patients showed preference toward treatment for RAI-R DTC over watchful waiting. Patients’ concerns about the risk of severe hypertension appeared to have had a greater effect on patients’ choice than severe proteinuria or HFSR

Do Patients and Physicians Have Similar Preferences for Chronic Hepatitis B Treatment Outcomes in Turkey?

Introduction: We aimed to quantify patients‘ and physicians’ preferences for therapeutic trade-offs involving the efficacy, side-effect risks, and evidence uncertainty in chronic hepatitis B (CHB) treatments. Materials and Methods: Physicians who treat CHB patients and adult patients with a self-reported physician diagnosis of CHB completed a web-enabled, discrete-choice experiment survey in Turkey. Both patients and physicians answered 12 treatment-choice questions. Each question required evaluating a pair of hypothetical CHB medication profiles defined by the years the medicine has been studied (weight of evidence), probability that the patient’s viral load remains undetectable for five years with possible reversal of disease progression (efficacy), five-year treatment-related risks of a fracture and renal insufficiency, and monthly medication cost. Logit models were used to estimate preference weights for all attribute levels and the profile preference scores for three current CHB treatments. A choice format conjoint analysis was used. Results: 159 physicians and 117 patients completed the survey. Patients and physicians had discordant views on the relative importance of CHB treatment attributes. Patients ranked weight of evidence and efficacy as the most important attributes, while physicians ranked efficacy and risk of renal insufficiency as the most important attributes. Both groups preferred a CHB medication profile characterized by potent efficacy and low side-effect risk versus a medication profile characterized by a potent efficacy and moderate side-effect risk profile (p> 0.05). Both medication profiles were preferred over a CHB medication with poor efficacy and low side-effect risk profile (p> 0.05 for patients and p< 0.05 for physicians). Conclusion: This is the first study to quantify patients’ and physicians’ preferences for CHB treatments in Turkey. Discordance between physicians’ and patients’ preferences can be explained by asymmetric knowledge and information regarding the importance of weight of evidence and efficacy versus side-effect risks. This fact highlights the need for reflection of physician and patient perspectives on regulatory and reimbursement decisions

How does cost matter in health‐care discrete‐choice experiments?

Willingness-to‐pay (WTP) estimates derived from discrete‐choice experiments (DCEs) generally assume that the marginal utility of income is constant. This assumption is consistent with theoretical expectations when costs are a small fraction of total income. We analyze the results of five DCEs that allow direct tests of this assumption. Tests indicate that marginal utility often violates theoretical expectations. We suggest that this result is an artifact of a cognitive heuristic that recodes cost levels from a numerical scale to qualitative categories. Instead of evaluating nominal costs in the context of a budget constraint, subjects may recode costs into categories such as ‘low’, ‘medium’, and ‘high’ and choose as if the differences between categories were equal. This simplifies the choice task, but undermines the validity of WTP estimates as welfare measures. Recoding may be a common heuristic in health‐care applications when insurance coverage distorts subjects' perception of the nominal costs presented in the DCE instrument. Recoding may also distort estimates of marginal rates of substitution for other attributes with numeric levels. Incorporating ‘cheap talk’ or graphic representation of attribute levels may encourage subjects to be more attentive to absolute attribute levels. Copyright (C) 2010 John Wiley & Sons, Ltd.willingness to pay , discrete‐choice experiments , decision heuristics , treatment cost ,

Understanding what matters to metastatic castration‐resistant prostate cancer (mCRPC) patients when considering treatment options: A US patient preference survey

Abstract Background Understanding how patients perceive the efficacy, safety, and administrative burden of treatments for metastatic castration‐resistant prostate cancer (mCRPC) can facilitate shared‐decision making for optimal management. This study sought to elicit patient preferences for mCRPC treatments in the US. Methods We conducted a cross‐sectional survey using the discrete‐choice experiment method. Participants were asked to state their choices over successive sets of treatment alternatives, defined by varying levels of treatment attributes: overall survival (OS), months until patients develop a fracture or bone metastasis, likelihood of requiring radiation to control bone pain, fatigue, nausea, and administration (i.e., oral/IV injection/IV infusion). Using mixed logit models, we determined the value (i.e., preference weights) that respondents placed on each attribute. Relative attribute importance (RAI) and marginal rates of substitution (MRS) were calculated to understand patients' willingness to make tradeoffs among different attributes. Results The final data set numbered 160 participants, with a mean age of 71.6 years old and a mean of 8.96 years since prostate cancer diagnosis. Participants' treatment preferences were as follows: OS (RAI: 31%), bone pain control (23%), nausea (16%), delaying fracture or bone metastasis (15%), fatigue (11%), and administration (3%). The MRS demonstrated that respondents were willing to trade 1.9 months of OS to eliminate moderate nausea and 3.3 months of OS for a reduction in fatigue from severe to mild. Conclusions Improving OS is the highest priority for patients with mCRPC, but they are willing to trade some survival to reduce the risk of requiring radiation to control bone pain, delay a fracture or bone metastasis, and experience less severe nausea and fatigue