Feasibility of Indirect Treatment Comparisons Between Niraparib Plus Abiraterone Acetate and Other First-Line Poly ADP-Ribose Polymerase Inhibitor Treatment Regimens for Patients with BRCA1/2 Mutation-Positive Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: Poly(ADP-ribose) polymerase inhibitors (PARPi) are a novel option to treat patients with metastatic castration-resistant prostate cancer (mCRPC). Niraparib plus abiraterone acetate and prednisone (AAP) is indicated for BRCA1/2 mutation-positive mCRPC. Niraparib plus AAP demonstrated safety and efficacy in the phase 3 MAGNITUDE trial (NCT03748641). In the absence of head-to-head studies comparing PARPi regimens, the feasibility of conducting indirect treatment comparisons (ITC) to inform decisions for patients with first-line BRCA1/2 mutation-positive mCRPC has been explored. METHODS: A systematic literature review was conducted to identify evidence from randomized controlled trials on relevant comparators to inform the feasibility of conducting ITCs via network meta-analysis (NMA) or population-adjusted indirect comparisons (PAIC). Feasibility was assessed based on network connectivity, data availability in the BRCA1/2 mutation-positive population, and degree of within- and between-study heterogeneity or bias. RESULTS: NMAs between niraparib plus AAP and other PARPi regimens (olaparib monotherapy, olaparib plus AAP, and talazoparib plus enzalutamide) were inappropriate due to the disconnected network, differences in trial populations related to effect modifiers, or imbalances within BRCA1/2 mutation-positive subgroups. The latter issue, coupled with the lack of a common comparator (except for olaparib plus AAP), also rendered anchored PAICs infeasible. Unanchored PAICs were either inappropriate due to lack of population overlap (vs. olaparib monotherapy) or were restricted by unmeasured confounders and small sample size (vs. olaparib plus AAP). PAIC versus talazoparib plus enzalutamide was not possible due to lack of published arm-level baseline characteristics and sufficient efficacy outcome data in the relevant population. CONCLUSION: The current randomized controlled trial evidence network does not permit robust comparisons between niraparib plus AAP and other PARPi regimens for patients with 1L BRCA-positive mCRPC. Decision-makers should scrutinize any ITC results in light of their limitations. Real-world evidence combined with clinical experience should inform treatment recommendations in this indication.

How are Companion Diagnostics Considered in Economic Evaluations of Oncology Treatments? A Review of Health Technology Assessments.

BACKGROUND: Companion diagnostic (CDx) testing is increasingly used to identify eligible patients for targeted treatments. Guidance on how CDx testing should be incorporated into cost-effectiveness models (CEM) is limited. This review evaluated how health technology assessment bodies and research organizations considered CDx in CEMs of targeted therapies in oncology and whether this ultimately impacted their decisions or time from regulatory approval to recommendations. METHODS: An exhaustive list of approved CDx tests in oncology was compiled. For corresponding indications and treatments, NICE appraisals published between 2016 and 2019 were identified. Then, assessments for the same treatments issued from 11 other agencies were reviewed. Data extracted included background and CDx information, CDx's role in the CEM, and recommendations. RESULTS: Twenty-seven NICE appraisals were identified; 15 considered CDx testing in the CEM, while 12 did not, mainly because testing had already been established for the comparators within the same class or in clinical practice from a prior treatment line. Both testing costs and mutation prevalence drove CDx testing costs per patient. The cross-comparison of assessments showed that CDx test characteristics were inconsistently reported. Time from regulatory approval to recommendations was not impacted by CDx cost inclusion in CEMs. CONCLUSION: CDx testing was included in cost-effectiveness models whenever mutation testing was required solely for patients receiving targeted treatment; cost per patient was based on test costs and mutation prevalence. It is unclear if expanded reliance on CDx testing will impact future assessments of targeted therapies. A future update is warranted to track trends over time.

Exacerbation Frequency And Eosinophil Counts Among Patients With COPD Currently Prescribed Triple Therapy.

Purpose: To characterize and estimate the proportion of patients with chronic obstructive pulmonary disease (COPD) who continue to exacerbate while receiving triple therapy and further describe these patients according to blood eosinophil counts. Methods: This was an analysis of the 2017 Adelphi Real-World Respiratory Disease Specific Programme (DSP) survey of patients with COPD from France, Germany, Italy, Spain, and the United Kingdom (UK). Demographics were assessed on the date of completion of the physician/patient questionnaire; clinical characteristics were captured for the previous 12 months. The proportion of patients receiving triple therapy, who had experienced ≥2 moderate or ≥1 severe acute exacerbations of COPD (AECOPD) in the 12 months prior to index, and had blood eosinophil counts ≥150 cells/µL (T-AECOPD-EOS150) or ≥300 cells/µL (T-AECOPD-EOS300), were calculated. Results: In total, 2876 patients were included of which 762 had an eosinophil value. A higher proportion of patients in the ≥300 cells/µL eosinophil group (55.9%) compared with 150-<300 cells/µL (48.7%) and <150 cells/µL (47.1%) groups experienced ≥2 moderate and/or ≥1 severe AECOPD in the year prior to index. The ≥300 cells/µL eosinophil group had the lowest reported level of health-related quality of life (HRQoL). More severe disease in terms of comorbidities, lung function, healthcare resource use, and HRQoL was seen in patients with ≥2 moderate or ≥1 severe AECOPD in the year prior to index while receiving triple therapy, compared with patients who did not meet these criteria. In total, 10.6% and 6.2% of the COPD population, respectively, met the criteria for the T-AECOPD-EOS150 and T-AECOPD-EOS300 cohorts. Conclusion: This analysis demonstrates that there is a subpopulation of patients with COPD who continue to experience exacerbations despite receiving triple therapy; approximately three-quarters of these had eosinophils ≥150 cells/µL and one-third had eosinophils ≥300 cells/µL; these patients may benefit from eosinophil-targeted therapies.

Patient Evaluation of Satisfaction and Outcomes with an Autoinjector for Self-Administration of Subcutaneous Belimumab in Patients with Systemic Lupus Erythematosus.

OBJECTIVE: This study assessed patient experiences of using an autoinjector device to self-administer subcutaneous belimumab for the treatment of systemic lupus erythematosus (SLE). Satisfaction, ease and convenience of use, and confidence with the device were assessed, in addition to overall experience with belimumab. METHODS: This cross-sectional study was conducted among patients who completed a phase IIb open-label, multi-dose usability, tolerability, and safety study of subcutaneous belimumab (NCT02124798), in which patients receiving intravenous belimumab or subcutaneous belimumab using a prefilled syringe were switched to eight weekly self-administered doses of subcutaneous belimumab using the autoinjector. This follow-up study comprised an online/paper questionnaire and qualitative telephone interviews. RESULTS: In total, 43 patients receiving belimumab completed the questionnaire, 21 of whom also completed a follow-up telephone interview. Qualitative interviews indicated that 17 of 21 (81%) patients had a positive experience using the autoinjector; all patients considered the autoinjector to be convenient. Of the 42 patients who switched from intravenous belimumab to the autoinjector, 32 (76%) expressed a preference for the autoinjector over intravenous administration; reasons included convenience, time saved, cost, and reduced injection pain. The most commonly reported disadvantage of the autoinjector was injection discomfort (n = 5 [24%]; qualitative interview). Compared with intravenous administration, the autoinjector improved ability to work (17 of 29 [59%] of those employed) and carry out daily activities (40%). CONCLUSION: Patients with SLE reported high levels of satisfaction with the belimumab autoinjector and preferred the autoinjector to intravenous administration, citing advantages such as time saved, cost, and improved ability to work and carry out daily activities.

Patient- and Physician-reported Satisfaction With Systemic Lupus Erythematosus Treatment in US Clinical Practice.

PURPOSE: This two-part study comprised two descriptive, cross-sectional surveys to evaluate treatment satisfaction among patients with systemic lupus erythematosus (SLE) and their physicians from US clinical practices. The Lupus Plus Project (LPP; part one) involved belimumab-containing regimens; the Disease Specific Program (DSP; part two) included all treatments and was designed to build on the body of evidence from part one. METHODS: The LPP recruited patients receiving belimumab, and comprised 2 paper questionnaires: a patient self-completion questionnaire (PSC) and a patient record form (PRF) completed by the physician. The DSP enrolled patients with SLE receiving any treatment and comprised four parts: a PSC, a PRF completed by the physician after patient consultation, face-to-face physician interviews, and a workload form completed by the physicians to indicate their total SLE patient workload. The key objective of this study was to assess physician and patient satisfaction with current treatment. FINDINGS: From the PSCs, data regarding patient-reported satisfaction with current treatment were available for 263 patients who were receiving belimumab combination therapy (LPP) and 250 patients who were receiving non-belimumab treatment (DSP). The majority of patients (belimumab, 86.3% [227/263]; non-belimumab, 78.4% [196/250]) responded positively (at least "somewhat satisfied") when asked about current treatment satisfaction, as did physicians (belimumab, 82.9% [311/375]; non-belimumab, 74.3% [326/439]). In multivariate analysis, factors most strongly associated with patient-reported satisfaction for patients receiving belimumab were patient-reported improvements in leisure activities since taking belimumab (odds ratio [OR] = 4.66), physician-reported improvements in fatigue (OR = 3.72), patient-reported improvements in general symptoms (OR = 3.02), and pain/achiness (OR = 2.71). Physician satisfaction was associated with clinical outcome such as improvements in pain/achiness (OR = 6.16), fatigue (OR = 3.76), and patient-reported satisfaction with treatment frequency (OR = 3.91). In patients receiving other SLE treatments, dosing frequency of current treatment (OR = 3.64) and a reduction in fatigue severity (OR = 3.61) were most strongly associated with patient-reported satisfaction; physician satisfaction was most strongly associated with a reduction in fatigue (OR = 6.22) and current remission status (OR = 6.05). IMPLICATIONS: When considering SLE treatment satisfaction patients tend to consider impact on daily functioning, whereas physicians take into account a wider range of clinical outcomes; however, both strongly consider improvements in fatigue. These surveys provide insights into treatment satisfaction among prescribers and patients with SLE. GSK-ClinicalStudyRegister.com identifiers: GSK study 202146 [HO 15-15509] and 205086 [HO 15-16709].

Development of the Systemic Lupus Erythematosus Steroid Questionnaire (SSQ): a novel patient-reported outcome tool to assess the impact of oral steroid treatment.

BACKGROUND: Oral glucocorticoids (steroids) are the mainstay of treatment for systemic lupus erythematosus (SLE), but their use is often associated with short- and long-term side effects. Following a literature review and discussions with patients with SLE, clinicians, and payers, a need was identified for a comprehensive SLE-specific tool that can be used to evaluate the side effects and benefits of steroids over time from a patient perspective. The objective of this study was to develop a patient-reported outcome (PRO) measure to assess general impact (baseline burden), benefits, side effects, and impacts associated with the use of oral steroids in patients with SLE. METHODS: A qualitative research protocol was developed in which adults with SLE currently receiving or who had received steroids in the past year were recruited from six US rheumatology practices to participate in concept elicitation (CE) interviews. The SLE Steroid Questionnaire (SSQ) was developed based on CE interview results and clinical input. Cognitive debriefing interviews with a second group of patients with SLE evaluated the content, clarity, and relevance of the items. The SSQ was refined using patient feedback, clinician review, and a translatability assessment. The protocol received central independent review board approval. RESULTS: Thirty-three patients (52% moderate disease severity; 58% currently receiving steroids, mean dose 8.7 mg/day) completed CE interviews. Patients reported benefits, side effects, and impacts from steroids. The refined SSQ contains 50 items assessing steroid dose/duration (4 items), general impact (baseline burden; 19 items), benefits (7 items), work/productivity (3 items), side effects (10 items), emotions (6 items), and overall satisfaction (1 item). CONCLUSION: The SSQ is a unique PRO, developed using robust scientific methodology in accordance with the Food and Drug Administration PRO Guidance. It was designed to comprehensively assess the patient experience with steroid therapy and better understand the benefits and burden of steroids for patients with SLE.

Treatment Satisfaction in Systemic Lupus Erythematosus: Development of a Patient-Reported Outcome Measure.

OBJECTIVE: The aim of this study was to develop a patient-reported outcome measure specific for systemic lupus erythematosus (SLE) to assess patient satisfaction with treatment, treatment options, and medical care. METHODS: Patients with SLE were recruited from four US rheumatology practices. Concept elicitation interviews identified aspects that patients considered important and relevant regarding satisfaction with treatment and medical care. Concept elicitation interviews and clinical input were used to draft the Lupus Satisfaction Questionnaire (LSQ). A second cohort of patients with SLE participated in combined concept elicitation/cognitive debriefing interviews, after which the LSQ was revised. RESULTS: Fourteen patients completed concept elicitation interviews: 93% were female, 57% were white, and 85% had moderate/severe SLE. Current treatments included hydroxychloroquine (93%), steroids (79%), and belimumab (57%), and 43% were biologic naive. Patients were generally satisfied with their treatment and medical care; however, they were dissatisfied with treatment adverse effects and the number of available treatment options. Cognitive debriefing interviews (n = 8) demonstrated that the LSQ was comprehensive, clear, and relevant; therefore, only minor revisions were made to the questionnaire. The LSQ assesses satisfaction with current SLE treatments (25 items), medical care (11 items), and insurance coverage (3 items). The draft LSQ was evaluated in 195 adults with SLE. Fifty-eight percent of patients reported that they were "somewhat satisfied" with their SLE treatment. CONCLUSIONS: The LSQ has been developed to assess treatment satisfaction among patients with SLE. Following further testing to support its validity and reliability, it will provide a useful tool to facilitate assessment of satisfaction with treatments for SLE and help inform treatment decisions.

A cost utility analysis of simeprevir used with peginterferon + ribavirin in the management of genotype 1 hepatitis C virus infection, from the perspective of the UK National Health Service.

INTRODUCTION: Triple therapy using a protease inhibitor (PI) with peginterferon and ribavirin (PR) is increasingly used in patients with chronic hepatitis C virus (HCV) infection. The most recently introduced PI, simeprevir (SMV), offers high levels of viral eradication combined with a reduced overall duration of therapy. The objective of this study was to compare the cost-effectiveness of SMV + PR vs PR alone or in combination with telaprevir (TVR) or boceprevir (BOC) in patients infected with genotype 1 HCV Method: A cost-utility model was constructed, incorporating two phases, capturing the efficacy of therapy in an initial treatment phase, followed by a long-term post-treatment Markov phase, capturing lifetime outcomes according to whether a sustained viral response (SVR) had been achieved on treatment. Dosage regimens were based on the EMA approved label for each treatment. SVR estimates and adverse event rates were derived from a mixed treatment comparison. Baseline characteristics were drawn from an analysis of a UK HCV data-set and clinician opinion. Health state transition probabilities, utilities, and health state costs were drawn from previously published economic analyses. The model considered direct health costs only, and the perspective was that of the UK National Health Service. RESULTS: The model yielded an ICER for SMV + PR vs PR alone of £9725/QALY for treatment-naïve and £7819/QALY for treatment-experienced. Benefit was driven by increased likelihood of achieving SVR, with consequent long-term utility gains. SMV + PR dominated TVR + PR and BOC + PR in both patient groups. This principally reflected the QALY benefit of an increased likelihood of SVR with SMV, combined with lower overall drug costs, due to reduced mean treatment duration. CONCLUSION: Compared to other currently licensed treatment options, SMV + PR represents a cost effective treatment option for patients with chronic genotype 1 HCV infection.

Reliability and validity of the Personal and Social Performance scale in patients with schizophrenia.

OBJECTIVE: The construct validity and test-retest reliability of the Personal and Social Performance (PSP) scale were used to assess social functioning in a cohort of ethnically diverse UK patients with schizophrenia. METHODS: A total of 73 patients with schizophrenia took part in the study. At baseline, the PSP, two symptomatology scales and two other functioning scales were administered. A subset of the sample (N=40) took part in a retest where the Clinical Global Impression-Severity (CGI-S) and PSP scales were administered 8-10 days later. RESULTS: PSP significantly correlated with all other measures, Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and Quality of Life Scale (QLS) at baseline (p<0.02) and with CGI-S at follow-up (p<0.01). In addition, the PSP scale was moderately sensitive to the severity of illness. Test-retest reliability for the PSP score was 0.45 and the scale was able to discriminate between known groups (mild and severe patients). CONCLUSION: The PSP was easy to administer in this predominantly inpatient cohort and was moderately correlated with all other functioning measures tested. Due to patient homogeneity, the test-retest reliability statistic of the PSP was lower than that observed in other studies.

Increased elastic tissue defect formation in the growth restricted Brown Norway rat: a potential link between in utero condition and cardiovascular disease.

Low birth weight for gestational age has been epidemiologically linked to cardiovascular mortality and morbidity in adult life. This study aimed to determine whether in utero growth restriction influences an early feature of atherosclerotic pathology; disruption of the aortic internal elastic lamina (IEL) in the adult Brown Norway (BN) rat. In utero growth restriction was induced by bilateral uterine artery ligation on day 18 of gestation, thereby decreasing newborn BN pup weight by approximately 14%. Restriction surgery significantly increased aortic IEL defect number at 8 wk of age in both sexes compared with no surgery animals (p < 0.002). At 16 wk of age placental restriction surgery significantly increased the number of defects in males compared with both no surgery and sham surgery control groups (p < 0.001). The total number of IEL defects was significantly correlated with several postnatal growth rate parameters, including 72-h postpartum weight. Neither blood pressure was significantly different between treatment groups, nor was it correlated with body weight or IEL defect numbers. The findings of this study seem to support the fetal origins of adult disease hypothesis, by demonstrating that a moderate growth restricting insult dramatically increases aortic elastic tissue defect formation via an apparently blood pressure-independent mechanism.