Non-Fusion Versus Fusion Surgery in Pediatric Idiopathic Scoliosis: What Trade-Offs in Outcomes Are Acceptable for the Patient and Family?

BACKGROUND: Vertebral body tethering and other non-fusion techniques for the treatment of pediatric idiopathic scoliosis are increasing in popularity. There is limited physician consensus on this topic as the result of a paucity of published data regarding which patients most benefit from non-fusion strategies. Thus, much of the decision-making is left to patients and parents, who must select a treatment based on their goals and values and the information available from health-care providers, the internet, and social media. We sought to understand patient and family preferences regarding the attributes of fusion versus non-fusion surgery that drive these choices. METHODS: Patients and families were recruited from 7 pediatric spine centers and were asked to complete a survey-based choice experiment that had been jointly developed with the U.S. Food and Drug Administration (FDA) to evaluate patient preferences. Choices between experimentally designed alternatives were analyzed to estimate the relative importance of outcomes and requirements associated with the choice options (attributes). The attributes included appearance, confidence in the planned correction, spinal motion, device failure, reoperation, and recovery period. The inclusion criteria were (1) an age of 10 to 21 years and (2) a diagnosis of adolescent idiopathic scoliosis in patients who were considering, or who had already undergone, treatment with fusion or non-fusion surgery. Preference weights were estimated from the expected changes in choice given changes in the attributes. RESULTS: A total of 344 respondents (124 patients, 92 parents, and 128 parent/patient dyads) completed the survey. One hundred and seventy-three patients were enrolled prior to surgery, and 171 were enrolled after surgery. Appearance and motion were found to be the most important drivers of choice. For the entire cohort, fusion was preferred over non-fusion. For patients who were considering surgery, the most important attributes were preservation of spinal motion and appearance. CONCLUSIONS: Patients and families seeking treatment for idiopathic scoliosis value appearance and preservation of spinal motion and, to a lesser extent, reoperation rates when considering fusion versus non-fusion surgery.

Patient Preferences Regarding Surgical Treatment Methods for Symptomatic Uterine Fibroids.

STUDY OBJECTIVE: The purpose of this study is to rank the factors that are most and least important to patients with symptomatic uterine fibroids when considering surgical treatment options. MATERIALS AND METHODS: Using a best worst scaling (BWS) preference elicitation approach, participants completed an online survey to rank factors associated with fibroid surgical treatments. Survey content was based on a literature review and included the following factors: symptom relief; surgical complications; repeat treatment; recovery time; cosmetic effects; risk of spreading undiagnosed cancer; sexual outcomes; maintenance of child-bearing; continuation of menses; unpredictable menses; and location of procedure. Participants completed 11 BWS tasks. For each task, we presented participants with a subset of 5 factors from the possible 11, and participants chose the most important and least important factor. Participants' responses were analyzed using conditional logistic regression to determine the relative importance of factors. Patient priorities were further explored via age and race. RESULTS: 285 respondents with symptomatic uterine fibroids (69 physician-confirmed and 216 self-reported) who had not undergone prior surgical treatment completed the survey. Respondents were enrolled from two clinical sites (clinical site cohort) and an online consumer panel (panel cohort). Both cohorts identified symptom relief, cancer risk, repeat treatment and complications as the most important factors in selecting surgical treatment options and location of procedure, return to normal activities after surgery, and cosmetic effects like presence of a scar after the surgical treatment as the least important factors. Of note, younger women (≤ 40) placed greater importance on the ability to have children after the procedure. CONCLUSION: Information regarding the factors most and least important to patients with symptomatic uterine fibroids might inform development and regulatory evaluation of new technologies and procedures. Study results may be useful in efforts to develop a set of outcomes to include in future fibroids clinical studies.

Patient-Centered Clinical Trial Design for Heart Failure Devices via Bayesian Decision Analysis.

BACKGROUND: The statistical significance of clinical trial outcomes is generally interpreted quantitatively according to the same threshold of 2.5% (in one-sided tests) to control the false-positive rate or type I error, regardless of the burden of disease or patient preferences. The clinical significance of trial outcomes-including patient preferences-are also considered, but through qualitative means that may be challenging to reconcile with the statistical evidence. OBJECTIVE: We aimed to apply Bayesian decision analysis to heart failure device studies to choose an optimal significance threshold that maximizes the expected utility to patients across both the null and alternative hypotheses, thereby allowing clinical significance to be incorporated into statistical decisions either in the trial design stage or in the post-trial interpretation stage. In this context, utility is a measure of how much well-being the approval decision for the treatment provides to the patient. METHODS: We use the results from a discrete-choice experiment study focusing on heart failure patients' preferences, questioning respondents about their willingness to accept therapeutic risks in exchange for quantifiable benefits with alternative hypothetical medical device performance characteristics. These benefit-risk trade-off data allow us to estimate the loss in utility-from the patient perspective-of a false-positive or false-negative pivotal trial result. We compute the Bayesian decision analysis-optimal statistical significance threshold that maximizes the expected utility to heart failure patients for a hypothetical two-arm, fixed-sample, randomized controlled trial. An interactive Excel-based tool is provided that illustrates how the optimal statistical significance threshold changes as a function of patients' preferences for varying rates of false positives and false negatives, and as a function of assumed key parameters. RESULTS: In our baseline analysis, the Bayesian decision analysis-optimal significance threshold for a hypothetical two-arm randomized controlled trial with a fixed sample size of 600 patients per arm was 3.2%, with a statistical power of 83.2%. This result reflects the willingness of heart failure patients to bear additional risks of the investigational device in exchange for its probable benefits. However, for increased device-associated risks and for risk-averse subclasses of heart failure patients, Bayesian decision analysis-optimal significance thresholds may be smaller than 2.5%. CONCLUSIONS: A Bayesian decision analysis is a systematic, transparent, and repeatable process for combining clinical and statistical significance, explicitly incorporating burden of disease and patient preferences into the regulatory decision-making process.

Quantifying Benefit-Risk Preferences for Heart Failure Devices: A Stated-Preference Study.

BACKGROUND: Regulatory and clinical decisions involving health technologies require judgements about relative importance of their expected benefits and risks. We sought to quantify heart-failure patients' acceptance of therapeutic risks in exchange for improved effectiveness with implantable devices. METHODS: Individuals with heart failure recruited from a national web panel or academic medical center completed a web-based discrete-choice experiment survey in which they were randomized to one of 40 blocks of 8 experimentally controlled choice questions comprised of 2 device scenarios and a no-device scenario. Device scenarios offered an additional year of physical functioning equivalent to New York Heart Association class III or a year with improved (ie, class II) symptoms, or both, with 30-day mortality risks ranging from 0% to 15%, in-hospital complication risks ranging from 0% to 40%, and a remote adjustment device feature. Logit-based regression models fit participants' choices as a function of health outcomes, risks and remote adjustment. RESULTS: Latent-class analysis of 613 participants (mean age, 65; 49% female) revealed that two-thirds were best represented by a pro-device, more risk-tolerant class, accepting up to 9% (95% CI, 7%-11%) absolute risk of device-associated mortality for a one-year gain in improved functioning (New York Heart Association class II). Approximately 20% were best represented by a less risk-tolerant class, accepting a maximum device-associated mortality risk of 3% (95% CI, 1%-4%) for the same benefit. The remaining class had strong antidevice preferences, thus maximum-acceptable risk was not calculated. CONCLUSIONS: Quantitative evidence on benefit-risk tradeoffs for implantable heart-failure device profiles may facilitate incorporating patients' views during product development, regulatory decision-making, and clinical practice.

Measuring Patient Preferences at the FDA Center for Devices and Radiological Health: Reflections and Projections.

OBJECTIVES: Patient preference information (PPI) is a way to incorporate the patient voice in the evaluation of medical devices. The US Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) has been working to encourage the voluntary inclusion of PPI throughout the medical device lifecycle for nearly a decade. This article reflects CDRH's efforts to encourage collection of PPI and offers perspectives on the future of PPI in the evaluation of medical devices. METHODS: CDRH regulatory guidance, public meetings, and collaborations relating to PPI were explored. RESULTS: Since 2012 when CDRH issued guidance on how PPI can be used as scientific evidence in the benefit-risk regulatory submission, CDRH has issued 5 subsequent guidance documents expanding on the use of PPI in medical device evaluations. CDRH remains committed to advancing the science and application of PPI in the medical device ecosystem through many collaborations with professional organizations, patient advocacy groups, and academic institutions. By hosting and actively participating in multiple scientific and regulatory public meetings and conferences, CDRH fosters a continuous learning environment where the experience of using PPI in regulatory submissions can be shared. A September 2020 meeting cosponsored by FDA and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) discussed the state of PPI in regulatory applications and beyond. CONCLUSION: This article describes these pivotal events that have helped to increase the use of PPI in medical device evaluation as well as discusses future applications of PPI.

The Value of Hope: Patients' and Physicians' Preferences for Survival in Advanced Non-Small Cell Lung Cancer.

PURPOSE: Immuno-oncology treatments offer patients with advanced non-small cell lung cancer (NSCLC) treatment options with greater probability of durable survival and a different toxicity profile compared with traditional chemotherapy. The objective of this study was to explore the importance of increases in the probability of long-term survival versus changes in expected (median) survival and treatment toxicities among patients with advanced NSCLC and physicians. PATIENTS AND METHODS: In a discrete-choice experiment, oncologists and patients diagnosed with NSCLC chose between profiles of treatments for advanced NSCLC offering different combinations of benefits (expected, best-case, and worst-case survival) and risks. We analyzed preference data from each sample using a random-parameters logit model that controls for preference heterogeneity and the panel nature of the data. RESULTS: Both patients and physicians expressed a strong preference for improving the probability of best-case survival; however, patients viewed increases in the probability of long-term survival as more important than increases in expected survival, while the opposite was true for physicians. Both patients and physicians weighted survival to be more important than toxicities. CONCLUSION: This study identified a potentially important divergence between physician and patient perspectives on survival statistics. Physicians placed more importance on increases in expected survival than did patients with NSCLC. The importance patients placed on long-term survival reinforce previous research identifying the primacy of hope as a value among seriously ill patients. The findings underscore the importance of considering patients' priorities and in shared decision-making when choosing treatment.

Patient Preferences for Preventive Migraine Treatments: A Discrete-Choice Experiment.

OBJECTIVE: To understand treatment preferences of people with migraine and the relative importance of improvements in efficacy and avoiding adverse events (AEs), such as cognition problems or weight gain. BACKGROUND: Current preventive migraine medicines are associated with poor adherence and tolerability. There is an unmet need for effective migraine-specific preventive treatments with fewer AEs. METHODS: In a web-based discrete-choice experiment survey, respondents who self-reported having ≥6 migraine days/month were offered choices between pairs of hypothetical preventive migraine medicines. Six attributes, each with 3 levels, defined the medicines: reduction in headache days per month (10%, 25%, or 50%), frequency of limitations with physical activities (none, 1-category improvement, or 2-category improvement), cognition problems (no problems, thinking problems, or memory problems), weight gain (none, 5% body weight gain, or 10% body weight gain), how the medicine is taken (daily oral pill, once-monthly injection, or twice-monthly injection), and monthly out-of-pocket cost ($5, $60, or $175). The attributes and levels were informed by clinician input, the clinical literature, and 2 focus groups. An experimental design was used to create the pairs of hypothetical medicines for the discrete-choice experiment questions. Random-parameters logit was used to estimate the relative importance of the medicine attributes, and the results were used to predict the percentage of respondents who would select one medicine profile over another and to calculate willingness to pay for changes in attribute levels. RESULTS: The sample included 300 respondents; 72% indicated that migraines make physical activities difficult all or most of the time, and 81% had taken a prescription medicine to prevent migraine in the last 6 months. Respondents reported having, on average, approximately 16 headache days per month. Among noncost attributes, respondents valued a change from a 10% reduction in migraine days to a 50% reduction more highly than avoiding the worst levels of AEs, but were willing to trade off efficacy for less-severe AEs. Avoiding memory problems was more important than avoiding thinking problems. Avoiding a 10% weight gain was more important than avoiding thinking and memory problems. Respondents preferred a once-monthly injection or daily pill to twice-monthly injection. Respondents, on average, were willing to pay $84 (95% confidence interval [CI], $64-$103) per month to avoid a 10% weight gain, $59 (95% CI, $42-$76) per month to avoid memory problems, $35 (95% CI, $20-$51) per month to avoid a 5% weight gain, and $32 (95% CI, $18-$46) per month to avoid thinking problems. CONCLUSIONS: A preventive migraine medicine with improved efficacy and AE profile and a favorable mode of administration would be valuable to migraine sufferers. Patients may be willing to trade off efficacy for better AE profiles. Clinicians should work with patients to select treatments that meet each patient's needs.

Comparing the Relative Importance of Attributes of Metastatic Renal Cell Carcinoma Treatments to Patients and Physicians in the United States: A Discrete-Choice Experiment.

OBJECTIVES: Value assessments of new treatments for metastatic renal cell carcinoma (RCC) should include outcomes that are most important to patients. This study aimed to quantify and compare the conditional relative importance of the attributes of RCC treatments to patients and physicians in the United States. METHODS: Patients with RCC and physicians who treat RCC completed an online discrete-choice experiment survey with a fractional factorial D-optimal experimental design. In a series of 12 questions, respondents chose between two hypothetical treatments defined in terms of six attributes: progression-free survival (PFS), probability of living ≥ 3 years (PL3Y), skin reactions, severity of fatigue, mode of administration, and monthly co-payment. Treatment choices were analyzed using a random-parameters logit model to estimate relative preference weights for the attribute levels and conditional relative attribute importance (i.e. the importance of an attribute relative to all other attributes conditional on the range of levels of that attribute). RESULTS: Overall, 201 patients and 142 physicians completed the survey. For both patients and physicians, PL3Y was the attribute with the greatest and statistically significant conditional relative importance. Estimates of the conditional relative importance of PFS, skin reactions, and mode of administration for patients, and for PFS and mode of administration for physicians, were not statistically significant. The preferences for improvements in PFS were independent of the level of PL3Y for both patients and physicians. Conditional relative attribute importance varied by patient disease stage. CONCLUSIONS: Patients and physicians indicated that PL3Y was the most important treatment attribute and was significantly more important than PFS. Importance rankings differed between physicians and patients and between all patients and those with advanced/metastatic disease.

Preferences for Multiple Sclerosis Treatments: Using a Discrete-Choice Experiment to Examine Differences Across Subgroups of US Patients.

BACKGROUND: The growing number of treatments for relapsing multiple sclerosis (MS) provides opportunities to consider patient preferences in treatment decisions. METHODS: We designed a Web-based, discrete-choice experiment survey to analyze treatment preferences in patients with relapsing-remitting MS (RRMS). The survey presented hypothetical MS treatments defined by six attributes: risk of MS progression, time between relapses, risk of serious infection, treatment-related flu-like symptoms and gastrointestinal symptoms, and route and frequency of administration. Preference weights estimated with random-parameters logit were used to calculate importance scores and preference shares among three pairs of subsamples. RESULTS: Patients with a self-reported physician diagnosis of RRMS (N = 301) completed the survey: 56% rated their disability level as normal or mild; 43% currently used a self-injectable treatment. Respondents with normal or mild disability levels placed greater weight on avoiding injections with flu-like symptoms and risk of progression, whereas patients with worse disability placed greater weight on reducing risk of progression and risk of serious infection. Patients taking injectables placed the most weight on risk of progression and risk of serious infection, whereas respondents not taking injectables placed the most weight on route and frequency of administration. Differences in preferences between subgroups were significant (P < .05). The presence of common adverse events associated with daily pills and injectables altered predicted preferences for route of administration. CONCLUSIONS: Preferences of patients with RRMS varied depending on current treatment and disability level, especially regarding mode of administration. Considering patient preferences for treatment features may lead to higher treatment satisfaction and adherence.