Patient preferences for chronic lymphocytic leukemia treatments: a discrete-choice experiment.

Aim: Patient preferences for the features of targeted chronic lymphocytic leukemia (CLL) therapies may differ. Materials & methods: A discrete-choice experiment (DCE) survey was administered to 229 respondents recruited through the CLL Society. Results: Respondents placed most importance on increasing the chance of progression-free survival (PFS) at 2 years from 70 to 90% and confirming results with measurable residual disease (MRD) testing instead of routine testing. Respondents also preferred daily oral administration over intravenous infusion every 4 weeks, fixed-duration treatments over treat-to-progression treatments and treatments with lower side effect risks. Reducing risk of tumor lysis syndrome was least important relative to changes in other attributes. Conclusion: The combination of improving PFS combined with confirming results using MRD testing was more important than changes in all other study attributes included in the DCE. Results from this study can help inform shared decision-making when selecting therapies for CLL.

Several targeted treatments are available for people with chronic lymphocytic leukemia (CLL). These treatments target specific proteins present in CLL cancer cells. They differ in how long they keep cancer from progressing, how the results are measured and the side effects they cause. Some targeted CLL treatments are taken as a daily pill, and others are given by intravenous infusion. Some targeted treatments are given for a fixed amount of time, and others are given until CLL progresses. We surveyed 229 US patients with CLL to understand what features they most value in a targeted CLL treatment. Survey participants were recruited through the CLL Society, a nonprofit organization devoted to education, support, advocacy and research for the CLL community. Survey results indicated that participants placed the most importance on increasing the chance that the cancer would not progress after 2 years from 70 to 90% and confirming results with measurable residual disease testing (which can detect minute levels of leukemia cells) instead of routine testing. Participants also preferred taking a pill every day over receiving an intravenous infusion every 4 weeks and preferred treatments given for a fixed amount of time over treatments given until CLL progresses. Participants preferred treatments with lower chances of tumor lysis syndrome (a potentially organ-damaging condition that may result following treatment), irregular heartbeat and fatigue. It is important for doctors to understand the treatment features that matter to people living with CLL so that they can work with patients individually to choose the right treatment.

Treatment preferences among patients with mild-to-moderate atopic dermatitis.

Study purpose: New treatments for atopic dermatitis (AD) are emerging; however, little is known about the treatment preferences of patients with mild-to-moderate AD. To measure patients' preferences, a cross-sectional, web-based discrete choice experiment (DCE) survey was developed and administered to 300 adults in the United States with a self-reported physician diagnosis of mild-to-moderate AD.Materials and methods: In the DCE, respondents evaluated pairs of hypothetical AD treatment profiles defined by efficacy, risk, and mode and frequency of administration attributes. The DCE data were analyzed using a random parameters logit model. Subgroup analysis was used to investigate preference heterogeneity.Results: The results revealed achieving clear or almost clear skin within 3-4 months of treatment was the most important attribute relative to all other study attributes. The results indicated that a topical cream applied twice daily was preferred to systemic treatments. Subgroup analysis revealed that respondents with lower self-assessed disease burden were more likely to choose topical over systemic treatments and less averse to the risk of pain, burning, and/or stinging from the medicine (all other treatment features remaining equal) than respondents with higher self-assessed disease burden.Conclusion: The results of this study can help inform shared decision-making to manage mild-to-moderate AD.

Experiences and Treatment Preferences in Patients With Psoriatic Arthritis: A Cross-Sectional Study in the ArthritisPower Registry.

INTRODUCTION: Despite recent advances in treatment for psoriatic arthritis (PsA), many patients experience inadequate response or intolerance to therapy, indicating that unmet treatment-related needs remain. To further characterize these unmet needs, we evaluated patients' experiences regarding the burden of PsA symptoms and disease impacts, and patients' preferences for treatment. METHODS: Patients from ArthritisPower, a rheumatology research registry, completed a web-based survey. Object case best-worst scaling (BWS) was used to evaluate the relative burden of 11 PsA-related symptoms and the relative importance of improvement in nine PsA-related disease impacts. BWS data were analyzed using a random-parameters logit model. Patient demographics, preferences for mode and frequency of therapy, and preferences for methotrexate were analyzed descriptively. RESULTS: Among the 332 participants, most were White (94%), female (80%), with mean age of 54 years (SD 11.4). In the BWS, joint pain was the most bothersome symptom, followed by other musculoskeletal pain and fatigue. The BWS for disease impacts found that improvements in the ability to perform physical activities were most important, followed by improvements in the ability to function independently, sleep quality, and the ability to perform daily activities. The most burdensome symptoms and desired disease impact improvements were similar in patients regardless of their experience with biologic disease-modifying antirheumatic drugs. The most preferred mode and frequency of treatment administration was oral, once-daily medication (preferred by 38% of respondents), and 74% prioritized therapies that significantly improved joint-related symptoms versus psoriasis-related symptoms. The majority of respondents (65%) preferred PsA treatment regimens that did not include methotrexate. CONCLUSIONS: Patients with PsA from a rheumatology registry found musculoskeletal pain symptoms to be the most bothersome and prioritized improvements to functional impacts of their disease. These findings can better inform development of new therapies and guide shared patient-provider treatment decision-making.

Preferences for herpes zoster vaccination among adults aged 50 years and older in the United States: results from a discrete choice experiment.

BACKGROUND: Most adults, and disproportionately fewer African-Americans, have not received herpes zoster (HZ) vaccination despite current recommendations. This study (GSK study identifiers: 208677/HO-17-18066) assessed HZ vaccination preferences among adults aged ≥ 50 years. RESEARCH DESIGN AND METHODS: In this discrete choice experiment, respondents chose among a 'no vaccine' option and two HZ vaccine profiles, characterized by seven attributes, in a series of choice questions. Random-parameters logit results were used to predict likely vaccine uptake. Subgroup and latent class analysis of African-American's preferences were performed. RESULTS: The preference weight for choosing HZ vaccines over no vaccine was statistically significant among the 1,454 respondents (71.9% whites; 25.2% African-Americans). Out-of-pocket (OOP) cost and vaccine effectiveness (VE) were the most important attributes. The African-American and the non-African-American subgroups had statistically significant differences in preferences (χ2 = 59.91, p < 0.001), mainly driven by OOP cost and VE. Latent class analysis identified three groups of African-American respondents with systematically different preferences; two comprised likely-vaccinators, with one being more cost sensitive at lower price thresholds, and one likely non-vaccinators. CONCLUSIONS: For all respondents, HZ vaccine choices were most sensitive to total OOP cost, followed by VE.

PLAIN LANGUAGE SUMMARYWhat is the context?Herpes zoster, or shingles, is a viral disease characterized by a painful, localized skin rash. It affects approximately 32% of US citizens at least once in their lifetime.The risk of contracting shingles increases with age.Most American adults over 50 years have not received the shingles vaccine, and vaccination rates are especially low for African-Americans. What is new?This is the first study to evaluate what drives shingles vaccination decisions among US adults ≥ 50 years of age. We also assessed the differences between African-American and non-African-American adults, and inside the African-American group.In this choice experiment, 1,454 people ≥ 50 years completed a survey of 8 choice questions, as well as questions on their previous experiences with vaccines, socioeconomic, and demographic characteristics. Seven factors were evaluated.We found that American adults preferred to get vaccinated, and the most influential factors were costs and vaccine effectiveness while location of vaccination was the least important. There were differences in preferences between African-American and non-African-American adults, mainly driven by costs and vaccine effectiveness. 3 different groups of African-American adults with systematically different preferences could be identified; two were likely to vaccinate, with one being more cost sensitive at lower price thresholds, and the third was unlikely to vaccinate.What is the impact?Decisions on shingles vaccination appear to be mostly driven by costs, which could be a barrier to those who do not have appropriate insurance, especially among some African-Americans.However, healthcare professionals should continue to educate patients on other vaccine characteristics, as they also influence vaccination decisions.

Risk tolerance in adjuvant and metastatic melanoma settings: a patient perspective study using the threshold technique.

Background: Adverse events (e.g., pyrexia) may affect treatment patterns and adherence. This study explored pyrexia risk tolerance among melanoma patients when treatment benefit is unknown versus known. Materials & methods: US respondents with stage III (n = 100) or stage III unresectable/stage IV melanoma (n = 125) chose between hypothetical melanoma treatments, defined by reoccurrence/progression-free survival and pyrexia risk, one resembling standard-of-care and one resembling dabrafenib + trametinib. Respondents chose first when efficacy was unknown and then when efficacy was known; pyrexia risk was varied systematically to define maximum acceptable risk. Results: Maximum acceptable risk of pyrexia was statistically significantly higher when efficacy was known versus unknown in stage III patients (85 vs 34%) and stage III unresectable/stage IV patients (66 vs 57%). Conclusion: Patients accepted higher levels of pyrexia risk when they understood treatment benefit.

Preferences for Adult Pneumococcal Vaccine Recommendations Among United States Health Care Providers.

INTRODUCTION: In 2014, the Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention (CDC) recommended 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) for all adults aged ≥ 65 years, with a commitment to revisit the recommendation for PCV13 because of declining vaccine-type disease. The Evidence-to-Recommendation framework used by the ACIP includes review of evidence regarding feasibility and stakeholder acceptability, but no surveys of vaccinator preferences have been published in the literature. METHODS: Physicians (N = 700), physician assistants (N = 100), pharmacists (N = 100), and nurse practitioners (N = 100) who recently prescribed, administered, or recommended adult pneumococcal vaccine were surveyed in March 2018. Object-case best-worst scaling was used to assess preferences among potential recommendation scenarios: retaining the then-current 2014 recommendation without a scheduled re-evaluation, retaining with a scheduled re-evaluation, revising PCV13 to Category B (retaining PPSV23 as Category A), removing PCV13 (retaining PPSV23 as Category A), and removing both PCV13 and PPSV23. RESULTS: Providers' most preferred recommendations were retaining the 2014 recommendation with another planned re-evaluation (52.6%) and retaining the then-current recommendation without planned re-evaluation (40.0%). Few preferred changing PCV13 to Category B (3.2%), removing PCV13 (3.7%), or removing both pneumococcal vaccines (0.5%). CONCLUSIONS: The majority of vaccinators surveyed preferred to retain the 2014 recommendation, either with another scheduled reassessment or indefinitely. FUNDING: Pfizer, Inc.

Patient and physician preferences for ulcerative colitis treatments in the United States.

Purpose: This study aimed to elicit patient and physician preferences for ulcerative colitis (UC) treatments in the United States (US). Patients and methods: The following UC treatment attributes included in the discrete-choice experiment (DCE) were identified during qualitative interviews with both patients and physicians: time to symptom improvement, chance of long-term symptom control, risks of serious infection and malignancy, mode and frequency of administration, and need for steroids. The DCE survey instruments were developed and administered to patients and physicians. A random-parameters logit model was used to estimate preference weights and conditional relative importance for these attributes. Results: A total of 200 patients with moderate to severe UC (status determined using self-reported medication history) and 200 gastroenterologists completed the survey. Patients' average age was 42 years; most (59%) were female. Patients considered symptom control 2.5 times as important as time to symptom improvement and 5-year risk of malignancy almost as important as long-term symptom control (relative importance, 0.79 vs 0.96 for long-term symptom control); they preferred oral to subcutaneous or intravenous administration (relative importance, 0.47 vs 0.11 and 0.18, respectively). For physicians, symptom control was the most important attribute and was five times as important as the risk of malignancy. Conclusion: Both patients and physicians considered long-term symptom control the most important attribute relative to others; however, risk of malignancy was of almost-equal importance to patients but not physicians. Differences between patients' and physicians' preferences highlight the need for improved communication about the relevant benefits and risks of different UC treatments to improve therapeutic decision-making.

Resonance Raman and resonance hyper-Raman intensities: structure and dynamics of molecular excited states in solution.

Resonance Raman scattering is discussed as a vibronic spectroscopy that can provide detailed information about the structure and dynamics of excited electronic states of molecules. The emphasis is on molecules in liquid solution. The theory of resonance Raman intensities and experimental and interpretive methods are discussed both in a historical context and in their present and future implementations. The related but much less developed technique of two-photon-resonant hyper-Raman scattering is also discussed in a similar context.

Resonance hyper-Raman spectra of zinc phthalocyanine.

Hyper-Raman spectra were obtained for zinc phthalocyanine in a dilute pyridine solution at excitation wavelengths that are two-photon resonant with the one-photon-allowed B band (360-380 nm) as well as with the two-photon absorption near 440 nm reported by Drobizhev et al. ( J. Chem. Phys. 2006, 124, 224701 ). In both regions, the hyper-Raman spectra were very different from the linear resonance Raman spectra at the corresponding excitation frequencies. While the resonance Raman spectra show only g symmetry modes, almost all of the hyper-Raman frequencies can be assigned as fundamentals of E u symmetry that also are observed in the infrared absorption spectrum or E u symmetry combination bands. These results contrast sharply with previous observations of highly noncentrosymmetric push-pull conjugated molecules and are consistent with a structure for phthalocyanine in solution that is centrosymmetric or nearly so. The hyper-Raman spectra show different intensity patterns in the two excitation regions, consistent with different Franck-Condon and/or vibronic coupling matrix elements for the different resonant states.

Automated parameter optimization in modeling absorption spectra and resonance Raman excitation profiles.

An automated method is described for optimizing the molecular parameters in simultaneous modeling of optical absorption spectra and resonance Raman excitation profiles. The method utilizes a previously developed Fortran routine that calculates absorption spectra and Raman excitation profiles for polyatomic molecules in solution from a model for the potential energy surfaces and spectral broadening mechanisms. It is combined here with an optimization routine from the commercial MATLAB package that iteratively adjusts the parameters of the molecular model to minimize the least-squared error between calculated and experimental spectra. Optimizations that typically require days to weeks of human time when performed interactively can be accomplished automatically in less than an hour of computer time. The method can handle large molecules (we show results for as many as 23 Raman-active modes) and mixtures of spectral broadening mechanisms (lifetime, Brownian oscillator, and inhomogeneous), and is robust toward noise or missing data points.

Solvent effects on resonant first hyperpolarizabilities and Raman and hyper-Raman spectra of DANS and a water-soluble analog.

The two-photon-resonant first hyperpolarizabilities associated with hyper-Rayleigh and hyper-Raman scattering are reported for 4-dimethylamino-4-nitrostilbene in 1,4-dioxane, dichloromethane, acetonitrile, and methanol, and for an ionic analog, 4-N,N-bis(6-(N,N,N-trimethylammonium)-hexyl)amino-4-nitrostilbene dibromide in methanol and water. Resonance Raman and hyper-Raman excitation profiles are also measured and modeled. The resonance Raman and hyper-Raman spectra show very similar relative intensities which do not vary much as the excitation frequency is tuned across the lowest-energy strong linear absorption band, suggesting that a single resonant electronic state dominates the one- and two-photon absorptions in this region. The absorption, resonance Raman, and hyper-Raman profiles can be simulated reasonably well with a common set of parameters. The peak resonant (absolute value of beta)2, measured by hyper-Rayleigh scattering, varies by about 50% over the range of solvents examined and shows a weak correlation with the linear absorption maximum, with the redder-absorbing systems exhibiting larger peak hyperpolarizabilities. The experimental hyper-Rayleigh intensities are higher than those calculated, possibly reflecting contributions from nonresonant electronic states.