A Systematic Literature Review of Health-related Quality of Life Measures for Women with Hypoactive Sexual Desire Disorder and Female Sexual Interest/Arousal Disorder.

INTRODUCTION: Hypoactive Sexual Desire Disorder (HSDD) / Female Sexual Interest/Arousal Disorder (FSIAD) impacts health-related quality of life (HRQoL) of women and their partners, yet existing measures fail to adequately capture relevant concepts (ie, what is essential to measure including symptoms/impacts) important to women with HSDD/FSIAD. OBJECTIVES: To identify HRQoL tools used to assess women with HSDD/FSIAD, and to evaluate their psychometric properties (ie, reliability, validity, and responsiveness). METHODS: We conducted searches in PubMed, Embase and PsychINFO from June 5, 1989 to September 30, 2020 for studies in women with HSDD/FSIAD and psychometric analyses (English only). Principles of the Preferred Reporting Items for Systematic reviews and Meta-Analyses, the COnsensus-based Standards for the selection of health Measurement INstruments Risk of Bias Checklist and other psychometric criteria were applied. Based on this search, 56 papers were evaluated including 15 randomized-controlled trials, 11 observational/single arm/open label studies, and 30 psychometric studies. RESULTS: Of the 18 measures identified, the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) were included in most studies (> 50%). General HRQoL instruments were not used in any of the clinical trials; the SF-12, SF-36 and EQ-5D-5L were reported in two observational studies. No instruments achieved positive quality ratings across all psychometric criteria. The FSFI, FSDS-R, Sexual Event Diary (SED) and the Sexual Desire Relationship Distress Scale (SDRDS), were the only measures to receive a positive rating for content validity. CONCLUSION: Reliable and valid HRQoL measures that include sexual desire and distress are needed to provide a more systematic and comprehensive assessment of HRQoL and treatment benefits in women with HSDD/FSIAD. While inferences about HRQoL are limited due to the lack of uniformity in concepts assessed and limited psychometric evaluation of these measures in women with HSDD/FSIAD, opportunities exist for the development of reliable and validated tools that comprehensively measure the most relevant and important concepts in women with HSDD/FSIAD. Lim-Watson MZ, Hays RD, Kingsberg S, et al. A systematic literature review of health-related quality of life measures for women with Hypoactive Sexual Desire Disorder and Female Sexual Interest/Arousal Disorder. Sex Med Rev 2022;10:23-41.

Will savings from biosimilars offset increased costs related to dose escalation? A comparison of infliximab and golimumab for rheumatoid arthritis.

INTRODUCTION: Biosimilar infliximab has the potential for appreciable cost savings compared to its reference biologic, but dose escalation is common and increases costs. We compared frequency of dose escalation and associated Medicare-approved amount so as to determine the break-even point at which infliximab dose escalation would offset the cost savings of using a biosimilar, referent to alternatively using golimumab. METHODS: We studied Medicare enrollees with rheumatoid arthritis (RA) initiating infliximab or golimumab. Frequency of dose escalation was summarized descriptively over 18 months, as were Medicare-approved amounts for reimbursement. Analyses were repeated conditioning on high adherence (i.e., non-discontinuation, > 10-week gap). Multivariable-adjusted logistic regression and mixed models evaluated factors associated with infliximab dose escalation. RESULTS: A total of 5174 infliximab and 2843 golimumab initiators were observed. Dose escalation was rare for golimumab (5%) but common for infliximab (49%), and was even more common (72%) for infliximab among patients who persisted on treatment. Regardless of dose escalation, the adjusted least square mean dollar amounts were appreciably higher for golimumab ($28,146) than for infliximab ($21,216) and greater among persistent patients (cost difference $9269, favoring infliximab). Only when patients escalated infliximab to ≥ 8 mg/kg every 6 weeks was golimumab IV at break-even or less expensive. After controlling for multiple factors, physician ownership of the infusion center was associated with greater likelihood of infliximab dose escalation (odds ratio = 1.25, 95% CI 1.09-1.44). CONCLUSION: Despite frequent dose escalation with infliximab that often increase its dose by threefold or more, the savings from the current price of its biosimilar substantially offsets the costs of an alternative infused TNFi biologic for which no biosimilar is available.

Problems with analyses and interpretation of data in "use of the KDQOL-36™ for assessment of health-related quality of life among dialysis patients in the United States".

A recent article in the journal reported analyses of KDQOL-36™ survey data collected from 240,343 adults (330,412 surveys) dialyzed at a large dialysis organization in the United States during 2014-2016. The authors concluded that the KDQOL-36™ Symptoms and Problems of Kidney Disease scale had the highest mean score of the KDQOL-36™ scales. We note that this inference was erroneous because the scales are not scored on the same numeric scale. In addition, the authors found that responses to a general health perceptions item ("In general, would you say your health is excellent, very good, good, fair, or poor") was not significantly associated with any of the 5 KDQOL-36 scale scores. In contrast, we find significant and noteworthy correlations in two other datasets. These analytic issues call into question the accuracy and validity of the conclusions of this paper.

Using Certification to Promote Uptake of Real-World Evidence by Payers.

Most randomized controlled trials are unable to generate information about a product's real-world effectiveness. Therefore, payers use real-world evidence (RWE) generated in observational studies to make decisions regarding formulary inclusion and coverage. While some payers generate their own RWE, most cautiously rely on RWE produced by manufacturers who have a strong financial interest in obtaining coverage for their products. We propose a process by which an independent body would certify observational studies as generating valid and unbiased estimates of the effectiveness of the intervention under consideration. This proposed process includes (a) establishing transparent criteria for assessment, (b) implementing a process for receipt and review of observational study protocols from interested parties, (c) reviewing the submitted protocol and requesting any necessary revisions, (d) reviewing the study results, (e) assigning a certification status to the submitted evidence, and (f) communicating the certification status to all who seek to use this evidence for decision making. Accrediting organizations such as the National Center for Quality Assurance and the Joint Commission have comparable goals of providing assurance about quality to those who look to their accreditation results. Although we recognize potential barriers, including a slowing of evidence generation and costs, we anticipate that processes can be streamlined, such as when familiar methods or familiar datasets are used. The financial backing for such activities remains uncertain, as does identification of organizations that might serve this certification function. We suggest that the rigor and transparency that will be required with such a process, and the unassailable evidence that it will produce, will be valuable to decision makers.

An Evaluation of Algorithms for Identifying Metastatic Breast, Lung, or Colorectal Cancer in Administrative Claims Data.

BACKGROUND: Administrative health care claims data are used for epidemiologic, health services, and outcomes cancer research and thus play a significant role in policy. Cancer stage, which is often a major driver of cost and clinical outcomes, is not typically included in claims data. OBJECTIVES: Evaluate algorithms used in a dataset of cancer patients to identify patients with metastatic breast (BC), lung (LC), or colorectal (CRC) cancer using claims data. METHODS: Clinical data on BC, LC, or CRC patients (between January 1, 2007 and March 31, 2010) were linked to a health care claims database. Inclusion required health plan enrollment ≥3 months before initial cancer diagnosis date. Algorithms were used in the claims database to identify patients' disease status, which was compared with physician-reported metastases. Generic and tumor-specific algorithms were evaluated using ICD-9 codes, varying diagnosis time frames, and including/excluding other tumors. Positive and negative predictive values, sensitivity, and specificity were assessed. RESULTS: The linked databases included 14,480 patients; of whom, 32%, 17%, and 14.2% had metastatic BC, LC, and CRC, respectively, at diagnosis and met inclusion criteria. Nontumor-specific algorithms had lower specificity than tumor-specific algorithms. Tumor-specific algorithms' sensitivity and specificity were 53% and 99% for BC, 55% and 85% for LC, and 59% and 98% for CRC, respectively. CONCLUSIONS: Algorithms to distinguish metastatic BC, LC, and CRC from locally advanced disease should use tumor-specific primary cancer codes with 2 claims for the specific primary cancer >30-42 days apart to reduce misclassification. These performed best overall in specificity, positive predictive values, and overall accuracy to identify metastatic cancer in a health care claims database.

Osteoporosis medication adherence: physician perceptions vs. patients' utilization.

Few data are available on physician perceptions of osteoporosis medication adherence. This study compared physician-estimated medication adherence with adherence calculated from their patients' pharmacy claims. Women aged ≥45 years, with an osteoporosis-related pharmacy claim between January 1, 2005 and August 31, 2008, and continuous coverage for ≥12 months before and after first (index) claim, were identified from a commercial health plan population. Prescribing physicians treating ≥5 of these patients were invited to complete a survey on their perception of medication adherence and factors affecting adherence in their patients. Pharmacy claims-based medication possession ratio (MPR) was calculated for the 12-month post-index period for each patient. Physicians who overestimated the percentage of adherent (MPR ≥0.8) patients by ≥10 points were considered "optimistic". Logistic regression assessed physician characteristics associated with optimistic perception of adherence. A total of 376 (17.2%) physicians responded to the survey; 62.0% were male, 58.2% were aged 45 to 60 years, 55.3% had ≥20 years of practice, and 35.4% practiced in an academic setting. Participating physicians prescribed osteoporosis medications for 2748 patients with claims data (mean [SD] age of 62.0 [10.6] years). On average, physicians estimated 67.2% of their patients to be adherent; however, only 40% of patients were actually adherent based on pharmacy data. Optimistic physicians (73.4%) estimated 71.9% of patients to be adherent while only 32.2% of their patients were adherent based on claims data. Physicians in academic settings were more likely to be optimistic than community-based physicians (odds ratio 1.69, 95% CI: 1.01, 2.85). Overestimation of medication adherence may impede physicians' ability to provide high quality care for their osteoporosis patients.

Patterns of osteoporosis treatment change and treatment discontinuation among commercial and Medicare Advantage Prescription Drug members in a national health plan.

RATIONALE, AIMS AND OBJECTIVES: Multiple treatments are available for osteoporosis; however, little is known about treatment change patterns and associated factors. Osteoporosis treatment change patterns, discontinuation and factors associated with treatment change in members of a large national health plan were examined. METHODS: A retrospective cohort study was conducted in 7315 commercial and 34 146 Medicare Advantage Prescription Drug (MAPD) members newly initiated on an osteoporosis medication between 2006 and 2008. Osteoporosis treatment change, discontinuation and re-initiation patterns were assessed. Multivariate logistic regression was used to examine factors associated with treatment change. Commercial and MAPD members were assessed separately because of differences in demographics and insurance benefits. RESULTS: Approximately 12% of members had a change in index therapy within 12 months. Almost 60% of members discontinued the index medication at least once, based on a 90-day refill gap. Over 40% of members discontinued all osteoporosis medications by the end of 12 months post-index. Among MAPD and commercial members, women and those with risedronate, ibandronate or calcitonin at index, index therapy in 2008 and an osteoporosis diagnosis were more likely to have a treatment change while members with health plans other than health maintenance organizations and generic alendronate at index were less likely to have a treatment change. CONCLUSIONS: Osteoporosis treatment change occurred in approximately 12% of members, while a greater proportion of members discontinued treatment completely within 12 months. Member characteristics may be used to predict therapy change for evaluation and quality initiatives within a health plan.

Identification of metastatic cancer in claims data.

PURPOSE: To develop algorithms to identify metastatic cancer in claims data, using tumor stage from an oncology electronic medical record (EMR) data warehouse as the gold standard. METHODS: Data from an outpatient oncology EMR database were linked to medical and pharmacy claims data. Patients diagnosed with breast, lung, colorectal, or prostate cancer with a stage recorded in the EMR between 2004 and 2010 and with medical claims available were eligible for the study. Separate algorithms were developed for each tumor type using variables from the claims, including diagnoses, procedures, drugs, and oncologist visits. Candidate variables were reviewed by two oncologists. For each tumor type, the selected variables were entered into a classification and regression tree model to determine the algorithm with the best combination of positive predictive value (PPV), sensitivity, and specificity. RESULTS: A total of 1385 breast cancer, 1036 lung, 727 colorectal, and 267 prostate cancer patients qualified for the analysis. The algorithms varied by tumor type but typically included International Classification of Diseases-Ninth Revision codes for secondary neoplasms and use of chemotherapy and other agents typically given for metastatic disease. The final models had PPV ranging from 0.75 to 0.86, specificity 0.75-0.97, and sensitivity 0.60-0.81. CONCLUSIONS: While most of these algorithms for metastatic cancer had good specificity and acceptable PPV, a tradeoff with sensitivity prevented any model from having good predictive ability on all measures. Results suggest that accurate ascertainment of metastatic status may require access to medical records or other confirmatory data sources.

Direct healthcare costs of osteoporosis-related fractures in managed care patients receiving pharmacological osteoporosis therapy.

BACKGROUND: Osteoporosis is a common condition and the economic burden of osteoporosis-related fractures is significant. While studies have reported the incremental or attributable costs of osteoporosis-related fracture, data on the economic impact of osteoporosis-related fractures in commercial health plan populations are limited. OBJECTIVE: To estimate the direct costs of osteoporosis-related fractures among pharmacologically treated patients in a large, commercially insured population between 2005 and 2008. METHODS: In this retrospective cohort study, patients were identified from a large, commercially insured population with integrated pharmacy and medical claims. Inclusion criteria were age 45-64 years; one or more osteoporosis medication claim(s) with first (index) claim between 1 January 2005 and 30 April 2008; and continuous insurance coverage for ≥12 months pre-index and ≥6 months post-index. Patients with pre-index Paget's disease or malignant neoplasm; skilled nursing facility stay; combination therapy at index; or fracture ≤6 months post-index were excluded. A generalized linear model compared differences in 6-month pre-/post-event costs for patients with and without fracture. Propensity score weighting was used to ensure comparability of fracture and non-fracture patients. Generalized estimating equations accounted for repeated measures. RESULTS: The study included 49,680 patients (2613 with fracture) with a mean (SD) age of 56.4 (4.7) years; 95.9% were female. Mean differences between pre- and post-event direct costs were $US14,049 (95% CI 7670, 20,428) for patients with vertebral fractures, $US16,663 (95% CI 11,690, 21,636) for patients with hip fractures, and $US7582 (95% CI 6532, 8632) for patients with other fractures. After adjusting for covariates, osteoporosis-related fractures were associated with an additional $US9996 (95% CI 8838, 11,154; p < 0.0001) in direct costs per patient across all fracture types during the 6 months following fracture. CONCLUSION: Patients with osteoporosis-related fractures were found to incur nearly $US10,000 in estimated additional direct healthcare costs in the 6 months post-fracture, compared with patients with no fracture. Reduced fracture risk may lower associated direct healthcare costs.

Medication adherence and fracture risk among patients on bisphosphonate therapy in a large United States health plan.

The association between bisphosphonate adherence in the first 12 months after therapy initiation and subsequent fracture risk was examined. Patients were identified from a large, commercially-insured population with integrated pharmacy and medical claims. Eligible patients were aged ≥45 years, were new to osteoporosis therapy (no osteoporosis medication claims in prior year) with first (index) bisphosphonate claim between 1/1/2005 and 4/30/2008, and had continuous insurance coverage for ≥12 months pre- and post-index. Patients with fracture claims ≤12-months post-index were excluded. Adherence was assessed using the medication possession ratio (MPR) over 12-months post-index (i.e., sum of days' supply dispensed divided by 365 days). Patients with a MPR>0.8 were considered adherent. The follow-up period to assess incident fracture began at month 13. The analysis included 33,558 new bisphosphonate users with mean age (SD) 59.5 (9.3) years; 94.0% were female. Median MPR at 12 months was 0.61 for alendronate and risedronate; 0.58 for ibandronate. Proportionally more nonfracture patients (39.3%) had a MPR>0.8 compared with fracture patients (34.9%, p<0.001). In multivariate modeling of bisphosphonate users' experience, those with a MPR>0.8 had a 14% lower risk of subsequent fracture than those with MPR<0.5, after controlling for demographics, insurance type, select comorbidities, and other potential confounders (p=0.0459). In a large, commercially-insured population, suboptimal adherence with bisphosphonate treatment was associated with increased fracture risk even after controlling for potential confounders.

Development of a fatigue and functional impact scale in anemic cancer patients receiving chemotherapy.

BACKGROUND: This study was conducted to develop a brief measure of fatigue and functional impact in cancer patients with anemia. METHODS: Data were obtained from a multisite, phase 2 study of darbepoetin-alpha (n = 1,558). Eligible patients were >or=18 years with nonmyeloid malignancies and anemia (hemoglobin

Budget impact analysis of darbepoetin alfa every 3 weeks versus epoetin alfa every week for the treatment of chemotherapy-induced anaemia from a US payer's perspective.

OBJECTIVE: This analysis was conducted to compare the direct medical costs of treatment with darbepoetin alfa every 3 weeks (Q3W) and epoetin alfa every week (QW) in patients with chemotherapy-induced anaemia (CIA) from the payer's perspective. METHODS: An analysis was conducted from a US health plan perspective to compare the annual budget impact for CIA with darbepoetin alfa Q3W and epoetin alfa QW over a 16-week treatment period. Dosing regimens were obtained from registration clinical trials. RESULTS: Mean doses, including dose adjustments, were 375.6 microg Q3W for darbepoetin alfa and 43,187 U QW for epoetin alfa. Costs of medical resources included drug acquisition and administration costs. The base case analysis resulted in a per-patient budget impact of $8,544 and $8,667 for darbepoetin alfa and epoetin alfa, respectively. Per member per month cost was $0.90 for darbepoetin alfa and $0.91 for epoetin alfa, based on an estimate of 2,735 CIA patients in a health plan population of 2.17 million. The analysis was most sensitive to drug dose, treatment period and drug price. CONCLUSIONS: Results suggest that per-patient direct medical costs of CIA treatment, when initiated at labelled starting doses, are comparable for darbepoetin alfa Q3W and epoetin alfa QW.

Patient-reported outcomes: instrument development and selection issues.

At its most elemental, patient-reported outcomes (PRO) assessment involves asking the patients questions and evaluating their answers. Instrument developers need to be clear about what they want to know, from whom they want to know it and why, whether what they learned is credible, and whether they can interpret what they learned in the context of the research objectives. Because credible instrument development is neither inexpensive nor technically trivial, researchers must first determine that no available measure meets their research objectives. We suggest that the tasks of either reviewing current instruments or developing new ones originate from the same basic premise: PRO assessment requires a well-articulated conceptual framework. Once defined in the context of the research objectives, the conceptual framework needs to be adapted to the population of interest. We discuss how qualitative methods enrich the conceptual framework and facilitate the technical measurement tasks of item development, testing, and reduction. We recognize that PRO assessment stands at a technological crossroads with the increasingly frequent application of "modern" psychometric methods and discuss how innovations such as item banks and computer-adaptive testing will influence PRO instrument development. Although items are the essential building blocks for instruments, scales are the primary unit of analysis for PRO assessment, and we discuss methods for scoring and combining them. Finally, PRO assessment is meaningless if the key figure chooses not to cooperate. We consider how respondent burden influences the quality of PRO assessment.

Patient and caregiver time burden associated with anaemia treatment in different patient populations.

GOALS: Cancer patients treated with chemotherapy often develop anaemia. This cross-sectional analysis examined the effect of anaemia treatment on patient and caregiver time and activities. MATERIALS AND METHODS: The analysis included 9,920 patients from 646 US outpatient oncology centres. Patients completed a survey that contained questions about travel time, total time for the visit and other impacts. RESULTS: The mean time taken for a single clinic visit to receive anaemia treatment was 2.2 h. On average, patients receiving epoetin alfa required 17.6 h more than patients receiving darbepoetin alfa to complete a course of anaemia treatment. All patients in the study reported that they had to adjust at least one activity as a result of clinic visits. Older patients, women and patients from low-income areas were more likely to be accompanied during clinic visits. CONCLUSIONS: Reducing the number of clinic visits needed for anaemia treatment by using darbepoetin alfa may benefit patients.

Efficacy of darbepoetin alfa in alleviating fatigue and the effect of fatigue on quality of life in anemic patients with lymphoproliferative malignancies.

Anemia-related fatigue in cancer patients reduces health-related quality of life (HRQOL). These analyses evaluate the effect of hemoglobin level on fatigue and examine the relationship between improved fatigue and HRQOL. Data were collected during a multicenter, randomized trial involving 344 anemic patients with lymphoproliferative malignancies receiving chemotherapy and darbepoetin alfa or placebo. At baseline, interim study visits, and end of treatment, patients completed an HRQOL questionnaire. Improved hemoglobin levels were significantly associated (P < 0.001) with improved fatigue. Mean change in the Functional Assessment of Cancer Therapy (FACT) Fatigue score was 5.9 points greater when hemoglobin improved > 2 g/dl than when it declined. Patients experiencing a clinically meaningful improvement in fatigue reported significantly (P < 0.001) greater improvements in all other scales, except the FACT Social subscale. Managing anemia-related fatigue appears to have a positive impact on HRQOL, enhancing cancer patients' activity levels, mood, and perceived overall health.

The economic burden of anemia in cancer patients receiving chemotherapy.

BACKGROUND: Anemia is one of the most common hematologic complications of cancer and cytotoxic treatment. The economic burden associated with anemia in patients with malignancy has not yet been extensively studied. METHODS: Patients receiving chemotherapy within 6 months of initial cancer diagnosis were identified in a database of commercial health-care service claims and encounters. Patients with anemia were identified through a coded diagnosis of anemia, transfusion, or erythropoietin treatment. Exponential conditional mean models and a decomposition analysis were used to analyze mean 6-month health-care expenditures. RESULTS: Twenty-six percent (26%) of 2760 cancer patients with recently diagnosed invasive cancer treated with chemotherapy had anemia. Mean (SD) 6-month unadjusted total expenditures were 62,499 dollars (78,016 dollars) for anemic patients and 36,871 dollars (52,308 dollars) for nonanemic patients (P < 0.0001), with inpatient services representing the largest cost differential between the groups. The adjusted mean 6-month expenditure for the average anemic patient receiving chemotherapy was 57,209 dollars. If anemic patients had the same average health status as nonanemic patients, their predicted 6-month expenditures would have been 19% lower (46,237 dollars). Alternatively, if anemic patients had the same expenditure structure or parameter estimates as nonanemic patients, their predicted expenditures would have been 51% lower (27,847 dollars). Thus, for any given health status, treating a patient who is anemic is associated with considerably higher expenditures. CONCLUSIONS: Anemia among cancer patients receiving chemotherapy is associated with a substantial burden in terms of direct medical costs. Implications for the treatment of anemia are suggested by this research and should be confirmed in prospective studies.

Hemoglobin increase is associated with improved health-related quality of life in patients with cancer not receiving chemotherapy.

Anemia is becoming recognized as a substantial problem for patients with cancer who are not receiving chemotherapy. Recently, darbepoetin alfa has been shown to provide significant clinical benefits in this patient population. This analysis assesses the effect of change in hemoglobin levels on health-related quality of life (HRQOL) in these patients. Eligible patients had anemia (hemoglobin /= 3 points) were significantly (P < 0.05) associated with improvements in functional, physical, and emotional well-being, depression, anxiety, and global ratings of energy, activity, and overall health. In summary, an increase in hemoglobin was associated with a decrease in fatigue in patients with anemia associated with nonmyeloid malignancies who were not receiving chemotherapy.

Psychological outcomes associated with anemia-related fatigue in cancer patients.

This article examines the relationships between chemotherapy-induced anemia, fatigue, and psychological distress among anemic cancer patients with solid tumors. Patients participating in two randomized clinical trials evaluating the efficacy of darbepoetin alfa (Aranesp) completed a questionnaire at baseline, at the beginning of each chemotherapy cycle, and at the end of the 12-week treatment period. The questionnaire included four psychological distress outcomes: Brief Symptom Inventory (BSI) Depression and Anxiety, Functional Assessment of Cancer Therapy (FACT)-Emotional Well-Being, numeric rating scale of Overall Health, and the FACT-Fatigue subscale. Patients with a hemoglobin response of at least a 2 g/dL increase were more likely to experience meaningful improvements (at least 3 points) in FACT-Fatigue scores than nonresponders (55.0% vs 39.8%; P = .0004). Patients with meaningful improvements in FACT-Fatigue scores reported significantly greater improvements in each of the psychological outcomes relative to those without improved fatigue (P <.0001). For BSI Depression and Anxiety, the differences in mean change scores between patients with and without improved fatigue were 8.2 and 7.7, respectively. Improving the hemoglobin levels of patients undergoing chemotherapy and suffering from anemia-related fatigue has the potential to produce significant positive effects on patients' fatigue, depressive symptoms, anxiety, feelings of helplessness, and overall health.