International Society For Pharmacoeconomics And Outcomes Research Research Articles

Epidemiology and treatment patterns for locally advanced or metastatic urothelial carcinoma: a systematic literature review and gap analysis.

BACKGROUND: Several immuno-oncology (IO) agents targeting programmed death-1 or programmed death-ligand 1 (PD-1/L1) are approved second-line therapy options for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) previously treated with platinum-based chemotherapy or first-line options in patients ineligible for cisplatin whose tumors express PD-L1 or for any platinum-based chemotherapy regardless of PD-L1 expression levels. However, literature on the epidemiology of la/mUC is limited, and real-world treatment patterns are not well established, especially with respect to therapies used following IO. OBJECTIVES: To (a) report the epidemiology of urothelial carcinoma (UC) and la/mUC; (b) identify and summarize the published literature on la/mUC treatment patterns, including IO and post-IO treatment; and (c) identify evidence gaps. METHODS: A systematic literature review was conducted using Cochrane dual-reviewer methodology and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Literature databases and selected congress abstracts (2017-2018) were searched for retrospective studies published January 2013-August 2018 in English reporting epidemiological and treatment data (all lines of therapy) for adult patients with la/mUC. RESULTS: Among 6,584 database references and 1,832 congress abstracts screened, 45 publications (29 manuscripts, 1 poster, 15 abstracts; reporting 37 unique studies) were retained. All studies related to treatment patterns, and the majority were from the United States (n = 17), Japan (n = 8), and the United Kingdom (n = 5). Epidemiological data were not identified among the searches thus online registries were leveraged. Among the identified publications, 21 (20 unique) reported on cisplatin versus non-cisplatin regimens, 14 (8 unique) on IO, and 9 (7 unique) on vinflunine. Cisplatin use varied both within and among countries (ranging from 18.4% in 1 U.S. study to 87.9% in 1 Japanese study). The use of IO was higher in later lines of therapy, ranging from 1.4% to 7.9% as first-line therapy to 57.8% as second-line and 64.4% as third-line therapy. Among studies reporting IO discontinuation rates, 41.4%-71% of patients were reported to discontinue IO across the studies, and the median time to discontinuation ranged from 2.7 to 5.8 months. Only 25%-35.5% of patients received subsequent therapy following IO discontinuation; post-IO treatments varied widely. CONCLUSIONS: Additional published data on the country-specific epidemiology of UC and la/mUC are needed, including rates of progression from early-stage disease to la/mUC. There was large variation in treatment rates, particularly cisplatin use, within and across countries. The few published real-world IO studies reported high levels of discontinuation with only a small percentage of patients receiving subsequent therapy. As IO therapies continue to be granted regulatory approval in countries outside the United States and novel therapies gain approval in the post-IO setting, the treatment paradigm for patients with la/mUC is shifting, and future studies with more recent data will be required. DISCLOSURES: This study was funded by Astellas/Seagen. Hepp is an employee of and owns stock in Seagen. Shah was a contractor for Astellas Pharma at the time of the study and owns stock in Pfizer. Smoyer is an employee and shareholder of Envision Pharma Group, paid consultants to Seagen. Vadagam was an employee of Envision Pharma Group, paid consultants to Seagen, at the time of the study. Parts of these data have been presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2019 Annual Meeting; May 18-22, 2019; New Orleans, LA.

Complication-specific direct medical costs by body mass index for 13 obesity-related complications: a retrospective database study.

BACKGROUND: Obesity, a multifactorial disease associated with many severe complications, affects more than 40% of adults in the United States. OBJECTIVE: To quantify the cost burden of 13 obesity-related complications (ORCs), overall and by body mass index (BMI) class. METHODS: Adult patients (aged ≥ 18 years) with ≥ 1 medical claim with an ICD-9/10 diagnosis code for the ORC of interest were identified using linked data from IQVIA's Ambulatory Electronic Medical Records and PharMetrics Plus. Thirteen ORCs were separately assessed (asthma, dyslipidemia, gastroesophageal reflux disease [GERD], heart failure with preserved ejection fraction [HFpEF], hypertension, musculoskeletal pain, obstructive sleep apnea [OSA], osteoarthritis [OA] of the knee, polycystic ovary syndrome [PCOS], prediabetes, psoriasis, type 2 diabetes mellitus [T2DM], and urinary incontinence); ORC cohorts were not mutually exclusive. For each ORC, the first claim identified for the ORC from January 2010-December 2016 was termed the index date. Patients had continuous enrollment in the 1-year pre-index (without a diagnosis code of the specific ORC under study) and the 1-year post-index, with ≥ 1 BMI value in the 6-months pre-index. Patients with underweight (BMI < 18.5 kg/m2) and those with cancer or pregnancy were excluded. Complication-specific costs were identified as claims with a diagnosis code for the ORC (primary position only for hospitalizations) or ORC-specific medications or procedures. Baseline demographic/clinical characteristics and complication-specific costs over the 1-year follow-up were assessed for each ORC cohort, overall and by BMI class (18.5-24.9; 25.0-29.9; 30.0-34.9; 35.0-39.9; ≥ 40 kg/m2). The association between total complication-specific costs and BMI class was assessed by generalized linear regression model for each ORC, adjusting for baseline characteristics. RESULTS: The total number of patients that comprised the ORC cohorts ranged from 1,275 (HFpEF) to 101,784 (musculoskeletal pain). Across ORC cohorts, 41.6% (musculoskeletal pain) to 73.5% (OSA) had obesity (BMI ≥ 30 kg/m2). For 4 ORC cohorts, more than one fifth of patients had class III obesity (BMI ≥ 40 kg/m2): T2DM, OSA, PCOS, and HFpEF. Baseline mean Charlson Comorbidity Index score increased with increasing BMI class for most ORC cohorts. The most costly ORCs overall based on mean total 1-year cost were: OA of the knee ($3,697 [range from normal weight (BMI: 18.5-24.9 kg/m2) to class III obesity: $2,453-$4,518]), HFpEF ($3,586 [range: $3,402-$4,685]), OSA ($2,768 [$2,442-$2,974]), and psoriasis ($2,711 [$2,131-$3,292]). The highest cost differences (≥20%) were observed among those with class III obesity versus those with normal weight for these aforementioned ORCs, as well as for GERD ($1,719 [$1,484-$1,893]) and asthma ($1,531 [$1,361-$1,780]). Following adjustment, most cost comparisons by BMI class were significantly higher versus those for normal weight for 6 ORCs. CONCLUSIONS: ORCs are important drivers of the economic burden of obesity, indicating an unmet need for the treatment of obesity. Appropriate weight management may reduce ORC-associated costs. DISCLOSURES: This study and its publication were supported by Novo Nordisk. Divino, Anupindi, and DeKoven are employed by IQVIA, which received funding from Novo Nordisk for this study. Ramasamy, Eriksen, Olsen, and Meincke are employed by and shareholders of Novo Nordisk. Material reported in this manuscript was presented in an abstract accepted by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2020, to be published in Value in Health. There was no presentation at ISPOR 2020.

PDB28 MODEL-Based LONG-TERM Cost-Effectiveness of Once-Weekly Semaglutide Compared with Other GLP-1 Receptor Agonists in Type 2 Diabetes: A Systematic Literature Review

To systematically review the existing pharmacoeconomic literatures evaluating the long-term cost effectiveness associated with once-weekly semaglutide in type 2 diabetes. A systematic literature review up to 1st Apr 2020 in PubMed, web of science, and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) presentation database was conducted. All long-term cost-effectiveness studies assessing once-weekly semaglutide comparing with other glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) were included. A total of ten studies were identified, including eight studies based on the IQVIA Core diabetes model and two studies based on the Swedish Institute for Health Economics Cohort Model of T2D (IHE model). Results showed that once-weekly semaglutide reduced cumulative incidence and delayed time to onset of diabetes-related complications than all comparators, resulting in improvement of quality-adjusted life expectancy, and saving of complication cost over patient lifetime horizon. When comparing with dulaglutide, once-weekly semaglutide 0.5mg and 1.0mg were associated with a range of 0.02∼0.11 QALYs gained and 0.05∼0.34 QALYs gained, respectively. The total cost of once-weekly semaglutide was projected to be lower than dulaglutide in most of the studies. When comparing with exenatide extended-release, lixisenatide and liraglutide, once-weekly semaglutide 0.5mg and 1.0mg were associated with a range of 0.14∼0.39 QALYs gained and 0.13∼0.71 QALYs gained, respectively. The total cost of once-weekly semaglutide was projected to be lower or slightly higher, which varied from comparators. Results based on the IQVIA Core diabetes model and IHE model were similar. The treatment algorithm and criteria for treatment change assumed in the model simulation would be more important for the long-term projection than the economic model used. The current literature presents that compared with dulaglutide and other GLP-1 RAs, once-weekly semaglutide was considered dominated or highly cost-effectiveness treatment alternative for type 2 diabetes.

Assessing the association between medication adherence, as defined in quality measures, and disease-state control, health care utilization, and costs in a retrospective database analysis of Medicare supplemental beneficiaries using statin medications.

BACKGROUND: Adherence to medication, and related health and economic outcomes, is becoming increasingly important as populations age and as the number of Americans managing chronic conditions increases. The Pharmacy Quality Alliance (PQA) statin medication adherence measure is used in Medicare star ratings to evaluate health plan performance. Yet, limited evidence exists that investigates the association between statin medication adherence, as specified in the PQA adherence quality measure, and disease-state control, health care utilization, and costs. OBJECTIVE: To determine the association between adherence (≥80% proportion of days covered) and disease-state control, health care utilization, and health care costs for Medicare supplemental beneficiaries using statin medications eligible for inclusion in the PQA statin adherence quality measure. METHODS: This retrospective study used a cohort of eligible beneficiaries for inclusion in the PQA statin adherence measure with low-density lipoprotein (LDL) laboratory values from IBM MarketScan Medicare Supplemental Research Databases (2009-2015). A logistic regression model assessed the association between adherence and LDL control (controlled individuals had LDL levels ≤ 100 mg/dL). Health care utilization and costs during a 1-year period, from first statin medication claim, were compared between adherent and nonadherent groups using generalized linear models with log link and negative binomial distribution (utilization) or gamma distribution (costs), adjusting for covariates. Beta coefficients were used to compute cost ratios (CR) and rate ratios (RR). Cohort characteristics were assessed using t-tests, Wilcoxon rank sum tests, or chi-square tests. An a priori alpha level of 0.001 was used. RESULTS: The study cohort consisted of 77,174 beneficiaries, of whom 58,668 (76.0%) were classified as adherent to their statin medications. After controlling for other factors, odds of disease-state control were approximately 2 times higher among medication adherent beneficiaries compared with their nonadherent counterparts (OR = 2.192; 95% CI = 2.109-2.278). Multivariable analyses showed adherers experienced 4.7% fewer outpatient (RR = 0.953; 95% CI = 0.940-0.965) and 27.5% fewer inpatient (RR = 0.725; 95% CI = 0.687-0.766) visits; had 9.9% lower outpatient (CR = 0.901; 95% CI = 0.885-0.916) and 28.3% lower inpatient (CR = 0.717; 95% CI = 0.705-0.729) costs; 14.7% lower total costs (CR = 0.853; 95% CI =0.838-0.868); and 7.0% higher prescription drug costs (CR = 1.070; 95% CI = 1.052-1.089) than nonadherers. Adherence to statin medications was associated with a reduction in total costs of $157.32 per member per month. CONCLUSIONS: This retrospective database analysis demonstrated that statin adherence was associated with approximately twice the odds of having a controlled disease state compared with nonadherence in a large Medicare sample. Adherent beneficiaries had fewer outpatient and inpatient visits (lower utilization), lower outpatient and inpatient costs, and lower total costs, a calculated savings of $157.32 per member per month, despite having higher prescription drug costs. Finally, these results provide important new information by demonstrating that adherence (≥ 80%) is associated with lower health care costs in a short (1-year) time frame. DISCLOSURES: Funding for this study was provided by Pharmacy Quality Alliance; Merck & Co. (Kenilworth, NJ); and SinfoniaRx. All authors except Pickering and Black were employed by the University of Arizona College of Pharmacy or the Mel & Enid Zuckerman College of Public Health at the time of this study. Pickering is employed by the Pharmacy Quality Alliance, and Black is employed by Merck & Co. Chinthammit also reports employment with Eli Lilly and Company, and Campbell reports employment with the Pharmacy Quality Alliance. Axon reports grants from Arizona Department of Health Services, unrelated to this work. Warholak reports grants from Novartis and the Arizona Department of Health Services, unrelated to this work. This research was presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Annual Meeting 2019, May 18-22, 2019, in New Orleans, LA.

Investigation of Factors Considered by Health Technology Assessment Agencies in Eight Countries.

BackgroundHealth technology assessment (HTA) organizations play a crucial role in optimizing healthcare resources, but the factors influencing decision making vary by country.ObjectiveHTAs of cancer and hepatitis C drugs were evaluated across developed countries to understand differences in decision processes and criteria.MethodsThe HTA organizations evaluated are from France, Germany, Italy, Spain, the United Kingdom (UK), Australia, Canada and Japan. Economic evaluation types and 28 factors in the following categories were evaluated: clinical uncertainties/issues; disease/population/treatment consideration factors including National Institute for Health and Care Excellence’s (NICE) special circumstances factors (e.g. end-of-life and innovation); and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) additional value elements. Qualitative and correspondence analyses were conducted to assess the differences across organizations.ResultsIncremental cost-effectiveness ratio (ICER) using quality-adjusted life-year (QALY) was evaluated in Canada, the UK, Australia and Japan. The highest observed clinical uncertainties were clinical benefits and comparator. For cancer drugs, correspondence analysis showed France, Australia, Canada and the UK to have common attributes observed, such as unmet needs and stakeholder persuasion. In addition, the UK reported end-of-life, issues around current treatment and innovation, whereas Germany reported manageable/insignificant adverse events more frequently. Finally, fear of contagion, equity and scientific spillover value elements were only observed in Australia.ConclusionAlthough clinical factors play a predominant role in the decision to reimburse medicine, HTA organizations consider additional aspects as well. If the methodology of HTA was clearly outlined, there would be more transparency in HTA systems leading to better understanding amongst stakeholders about decision making.Electronic supplementary materialThe online version of this article (10.1007/s41669-020-00235-6) contains supplementary material, which is available to authorized users.

Cost-Effectiveness of Treatment Strategies with Biologics in Accordance with Treatment Guidelines for Ankylosing Spondylitis: A Patient-Level Model.

Ankylosing spondylitis (AS) is a form of rheumatic disease caused by chronic inflammation of the axial skeleton. Patients with AS experience significant functional limitations and reduced quality of life. Consequently, AS imposes a substantial economic burden on society due to productivity loss and work disability. Biologics, including tumor necrosis factor (TNF) inhibitors and human anti-interleukin-17A monoclonal antibody (IL-17A) agents, are effective treatment strategies in relieving symptoms and slowing down disease progression. Currently, 5 TNF inhibitors and 2 IL-17A antibody agents are approved by the FDA for the management of AS. Of these agents, there is no clear preferred agent in initial biologic therapy, although an IL-17A antibody agent or alternative TNF inhibitor agent is recommended after failure of the initial TNF inhibitor therapy. To assess cost-effectiveness of treatment strategies with biologics, TNF inhibitor or IL-17A, in accordance with the treatment guidelines for patients with AS. An economic patient-level simulation combining decision-tree and Markov models was constructed from the U.S. health care payer's perspective over a 10-year time horizon. The current model examined 5 treatment strategies: (1) conventional care treatment with nonsteroidal anti-inflammatory drugs, (2) 1 TNF inhibitor, (3) an IL-17A antibody agent, (4) sequential therapy with 2 TNF inhibitors, and (5) sequential therapy with a TNF inhibitor followed by an IL-17A antibody agent. Initially, treatment responses were determined after 12-week treatments. Patients who responded to treatment entered a "responders" Markov model. Patients entered a "nonresponders" Markov model if they inadequately responded to treatment. In sequential treatment strategies, patients who inadequately responded to treatment with the first TNF inhibitor received a second TNF inhibitor or an IL-17A antibody agent. Health utility was estimated based on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index (BASFI) scores. The models accounted for real-world adherence to TNF inhibitor treatment. Scenario and probabilistic sensitivity analyses were performed to test the robustness and uncertainty of the model results. Over a 10-year time horizon and 100,000 simulated patients for each treatment strategy, base-case results produced average total discounted per-patient costs of $19,765, $130,302, $159,934, $190,553, and $179,118 and quality-adjusted life-years (QALYs) of 4.675, 5.410, 5.499, 5.919, and 5.893 for conventional care, treatment strategies with 1 TNF inhibitor, an IL-17A, 2 TNF inhibitors, and a TNF inhibitor followed by an IL-17A, respectively. The optimal treatments at willingness-to-pay (WTP) thresholds ≤ $130,813 per QALY, between $130,813 per QALY and $442,728 per QALY, and > $442,728 per QALY were conventional care and sequential treatment strategies with 1 TNF inhibitor, followed by an IL-17A agent and 2 TNF inhibitors, respectively. Study findings suggested that all treatment strategies with biologics, TNF inhibitors or IL-17A antibody agents, in the treatment guidelines for AS were not cost-effective at the common WTP of $100,000 per QALY. However, the sequential treatment with 1 TNF inhibitor followed by an IL-17A antibody agent was considered cost-effective at a higher WTP of $150,000 per QALY. No outside funding supported this study. The authors have nothing to disclose. Primary findings of this study were presented in part at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) in Baltimore, MD, May 2018.

A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis.

BackgroundSince 2010, 27 mixed-treatment comparisons (MTCs) of disease-modifying therapies (DMTs) for multiple sclerosis have been published. However, there has been continued evolution in the field of MTCs. Additionally, limitations in methodological approach and reporting transparency, even in the most recent publications, makes interpretation and comparison of existing studies difficult.ObjectivesThe objectives of this study are twofold: (1) to estimate the efficacy and safety of DMTs at European Commission-approved doses compared with placebo in adults with relapsing–remitting multiple sclerosis (RRMS) using MTC, and (2) to identify and address methodological challenges when performing MTC in RRMS, thereby creating a baseline for comparisons with future treatments.MethodsSearches were completed in 14 databases, including MEDLINE, Embase, CENTRAL, CDSR and DARE, from inception to June 2018 to identify published or unpublished prospective, randomised controlled trials of all European Union-approved DMTs or DMTs expected to be approved in the near future in RRMS or rapidly-evolving severe RRMS. No language or date restrictions were applied. Studies were included in the MTC if they were judged to have sufficiently similar characteristics, based on the following: patient age; proportion of male participants; Expanded Disability Status Scale (EDSS) score; duration of disease; number of relapses prior to enrolment and proportion of previously treated patients. Background information from the included studies, as well as effect size and confidence intervals (where relevant) of defined outcomes were extracted. Reporting of the MTC was consistent with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) network meta-analysis guidelines.ResultsIn total, 33 studies were included in the MTC. Annualised relapse rate (ARR 28 trials) was significantly reduced in all treatments compared with placebo. Alemtuzumab had the highest probability (63%) of being the most effective treatment in terms of ARR compared with placebo (rate ratio [RR] 0.28, 95% credible interval [CrI] 0.21–0.38), followed by natalizumab (30% probability; RR 0.32, 95% CrI 0.23–0.43). The risk of 3- and 6-month confirmed disability progression (CDP3M, 13 trials; CDP6M, 14 trials) were similar; CDP6M was significantly reduced for alemtuzumab (hazard ratio [HR] 0.365; 95% CrI 0.165–0.725), ocrelizumab (HR 0.405, 95% CrI 0.188–0.853) and natalizumab (HR 0.459, 95% CrI 0.252–0.840) relative to placebo. There were no significant differences in the odds of serious adverse events (SAEs, 6 trials) between any treatment and placebo. The results of the MTC were limited by the lack of studies reporting direct comparisons between the included treatments and by heterogeneous reporting of key outcome data.ConclusionsMeta-analyses confirmed the benefit of all DMTs in terms of relapse rate compared with placebo with a comparable rate of SAEs for the DMTs that could be included in the network. The rigor and transparency of reporting in this study provide a benchmark for comparisons with future new agents.Electronic Supplementary MaterialThe online version of this article (10.1007/s40120-020-00212-5) contains supplementary material, which is available to authorized users.

Minimum volume standards in day surgery: a systematic review

BackgroundThe aim was to find out if and for what indications are minimum volume standards (MVS) applied in the day surgery setting and whether the application of MVS improves patient relevant outcomes.MethodsWe conducted a comprehensive systematic literature search in seven databases on July 12th, 2019. Concerning effectiveness and safety, the data retrieved from the selected studies were systematically extracted into data-extraction tables. Two independent researchers (MS, CS) systematically assessed the quality of evidence using the quality assessment tool for individual studies of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) called Task Force Checklist for Quality Assessment of Retrospective Database Studies. No instances of disagreement occurred. No further data processing was applied.ResultsThe systematic literature search, together with hand search, yielded 595 hits. No prospective or controlled studies were found. Data from eight retrospective studies were used in the analysis of clinical effectiveness and safety on seven indications: anterior cruciate ligament reconstruction, cataract surgery, meniscectomy, thyroidectomy, primary hip arthroscopy, open carpal tunnel release, and rotator cuff repair. All interventions (except for carpal tunnel release and thyroidectomy) confirmed a volume-outcome relationship (VOR) with relation to surgeon/hospital volume, however, none established MVS for the respective interventions. Safety related data were reported without its relationship to surgeon/hospital volume.ConclusionsThis present paper provides some evidence in favor of the VOR, however, it based on low quality retrospective data-analyses. The present results cannot offer any clear-cut MVS thresholds for the day surgery setting and so the simple transition from inpatient results (that support MVS) to the day surgery setting is questionable. Further quality assuring policy approaches should be considered.

Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review.

BackgroundCoronavirus disease 2019 (COVID‐19) is a rapidly emerging disease classified as a pandemic by the World Health Organization (WHO). To support the WHO with their recommendations on quarantine, we conducted a rapid review on the effectiveness of quarantine during severe coronavirus outbreaks.ObjectivesTo assess the effects of quarantine (alone or in combination with other measures) of individuals who had contact with confirmed or suspected cases of COVID‐19, who travelled from countries with a declared outbreak, or who live in regions with high disease transmission.Search methodsAn information specialist searched the Cochrane COVID‐19 Study Register, and updated the search in PubMed, Ovid MEDLINE, WHO Global Index Medicus, Embase, and CINAHL on 23 June 2020.Selection criteriaCohort studies, case‐control studies, time series, interrupted time series, case series, and mathematical modelling studies that assessed the effect of any type of quarantine to control COVID‐19. We also included studies on SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) as indirect evidence for the current coronavirus outbreak.Data collection and analysisTwo review authors independently screened abstracts and titles in duplicate. Two review authors then independently screened all potentially relevant full‐text publications. One review author extracted data, assessed the risk of bias and assessed the certainty of evidence with GRADE and a second review author checked the assessment. We used three different tools to assess risk of bias, depending on the study design: ROBINS‐I for non‐randomised studies of interventions, a tool provided by Cochrane Childhood Cancer for non‐randomised, non‐controlled studies, and recommendations from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) for modelling studies. We rated the certainty of evidence for the four primary outcomes: incidence, onward transmission, mortality, and costs.Main resultsWe included 51 studies; 4 observational studies and 28 modelling studies on COVID‐19, one observational and one modelling study on MERS, three observational and 11 modelling studies on SARS, and three modelling studies on SARS and other infectious diseases. Because of the diverse methods of measurement and analysis across the outcomes of interest, we could not conduct a meta‐analysis and undertook a narrative synthesis. We judged risk of bias to be moderate for 2/3 non‐randomized studies of interventions (NRSIs) and serious for 1/3 NRSI. We rated risk of bias moderate for 4/5 non‐controlled cohort studies, and serious for 1/5. We rated modelling studies as having no concerns for 13 studies, moderate concerns for 17 studies and major concerns for 13 studies.Quarantine for individuals who were in contact with a confirmed/suspected COVID‐19 case in comparison to no quarantineModelling studies consistently reported a benefit of the simulated quarantine measures, for example, quarantine of people exposed to confirmed or suspected cases may have averted 44% to 96% of incident cases and 31% to 76% of deaths compared to no measures based on different scenarios (incident cases: 6 modelling studies on COVID‐19, 1 on SARS; mortality: 2 modelling studies on COVID‐19, 1 on SARS, low‐certainty evidence). Studies also indicated that there may be a reduction in the basic reproduction number ranging from 37% to 88% due to the implementation of quarantine (5 modelling studies on COVID‐19, low‐certainty evidence). Very low‐certainty evidence suggests that the earlier quarantine measures are implemented, the greater the cost savings may be (2 modelling studies on SARS).Quarantine in combination with other measures to contain COVID‐19 in comparison to other measures without quarantine or no measuresWhen the models combined quarantine with other prevention and control measures, such as school closures, travel restrictions and social distancing, the models demonstrated that there may be a larger effect on the reduction of new cases, transmissions and deaths than measures without quarantine or no interventions (incident cases: 9 modelling studies on COVID‐19; onward transmission: 5 modelling studies on COVID‐19; mortality: 5 modelling studies on COVID‐19, low‐certainty evidence). Studies on SARS and MERS were consistent with findings from the studies on COVID‐19.Quarantine for individuals travelling from a country with a declared COVID‐19 outbreak compared to no quarantineVery low‐certainty evidence indicated that the effect of quarantine of travellers from a country with a declared outbreak on reducing incidence and deaths may be small for SARS, but might be larger for COVID‐19 (2 observational studies on COVID‐19 and 2 observational studies on SARS).Authors' conclusionsThe current evidence is limited because most studies on COVID‐19 are mathematical modelling studies that make different assumptions on important model parameters. Findings consistently indicate that quarantine is important in reducing incidence and mortality during the COVID‐19 pandemic, although there is uncertainty over the magnitude of the effect. Early implementation of quarantine and combining quarantine with other public health measures is important to ensure effectiveness. In order to maintain the best possible balance of measures, decision makers must constantly monitor the outbreak and the impact of the measures implemented.This review was originally commissioned by the WHO and supported by Danube‐University‐Krems. The update was self‐initiated by the review authors.

Improving transparency to build trust in real-world secondary data studies for hypothesis testing-Why, what, and how: recommendations and a road map from the real-world evidence transparency initiative.

Real-world data (RWD) and the derivations of these data into real-world evidence (RWE) are rapidly expanding from informing healthcare decisions at the patient and health system level to influencing major health policy decisions, including regulatory approvals and coverage. Recent examples include the approval of palbociclib in combination with endocrine therapy for male breast cancer and the inclusion of RWE in the label of paliperidone palmitate for schizophrenia. This interest has created an urgency to develop processes that promote trust in the evidence-generation process. Key stakeholders and decision-makers include patients and their healthcare providers; learning health systems; health technology assessment bodies and payers; pharmacoepidemiologists and other clinical reseachers, and policy makers interested in bioethical and regulatory issues. A key to optimal uptake of RWE is transparency of the research process to enable decision-makers to evaluate the quality of the methods used and the applicability of the evidence that results from the RWE studies. Registration of RWE studies-particularly for hypothesis evaluating treatment effectiveness (HETE) studies-has been proposed to improve transparency, trust, and research replicability. Although registration would not guarantee better RWE studies would be conducted, it would encourage the prospective disclosure of study plans, timing, and rationale for modifications. A joint task force of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE) recommended that investigators preregister their RWE studies and post their study protocols in a publicly available forum before starting studies to reduce publication bias and improve the transparency of research methods. Recognizing that published recommendations alone are insufficient, especially without accessible registration options and with no incentives, a group of experts gathered on February 25 and 26, 2019, in National Harbor, Maryland, to explore the structural and practical challenges to the successful implementation of the recommendations of the ISPOR/ISPE task force for preregistration. This positioning article describes a plan for making registration of HETE RWE studies routine. The plan includes specifying the rationale for registering HETE RWE studies, the studies that should be registered, where and when these studies should be registered, how and when analytic deviations from protocols should be reported, how and when to publish results, and incentives to encourage registration. Table 1 summarizes the rationale, goals, and potential solutions that increase transparency, in addition to unique concerns about secondary data studies. Definitions of terms used throughout this report are provided in Table 2.

Competencies for Professionals in Health Economics and Outcomes Research: The ISPOR Health Economics and Outcomes Research Competencies Framework.

The need for Health Economics and Outcomes Research (HEOR) has expanded globally, fueling demand for professionals trained in the discipline. By leveraging the expertise and perspectives of its members, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) established a set of competencies for HEOR professionals. The resulting 41 competencies were organized into 13 topic domains that collectively comprise the ISPOR Health Economics and Outcomes Research Competencies Framework. In this article, we explain the collaborative process used by the ISPOR Institutional Council and Faculty Advisor Council to identify and validate the framework. This process entailed expertise from the council members combined with natural language processing to examine competencies included in ISPOR Career Center HEOR job postings, qualitative input from a focused Institutional Council-Faculty Advisor Council workgroup, and quantitative input from 3 surveys of mutually exclusive member groups: a general member survey to assess importance and relevance of each competency, a faculty member survey to assess the extent to which HEOR graduate degree programs cover each of the competencies, and a student member survey to assess exposure to each of the competencies. Organization of the competencies into topic domains was achieved by engaging the Education Council, which applied a taxonomy consistent with ISPOR's educational programming. The resulting ISPOR Health Economics and Outcomes Research Competencies Framework has the important potential of serving as a tool to guide academic curricula, fellowships, and continuing education programs, and assessment of job candidates. As the HEOR field advances, so do the job types and the breadth of topics in which professionals must demonstrate competence. Future work will entail revisiting the competencies to ensure their currency and comprehensiveness, and tailoring the framework according to major specialty areas.

Improving Transparency to Build Trust in Real-World Secondary Data Studies for Hypothesis Testing-Why, What, and How: Recommendations and a Road Map from the Real-World Evidence Transparency Initiative.

Real-world data (RWD) and the derivations of these data into real-world evidence (RWE) are rapidly expanding from informing healthcare decisions at the patient and health system level to influencing major health policy decisions, including regulatory approvals and coverage. Recent examples include the approval of palbociclib in combination with endocrine therapy for male breast cancer and the inclusion of RWE in the label of paliperidone palmitate for schizophrenia. This interest has created an urgency to develop processes that promote trust in the evidence-generation process. Key stakeholders and decision-makers include patients and their healthcare providers; learning health systems; health technology assessment bodies and payers; pharmacoepidemiologists and other clinical reseachers, and policy makers interested in bioethical and regulatory issues. A key to optimal uptake of RWE is transparency of the research process to enable decision-makers to evaluate the quality of the methods used and the applicability of the evidence that results from the RWE studies. Registration of RWE studies-particularly for hypothesis evaluating treatment effectiveness (HETE) studies-has been proposed to improve transparency, trust, and research replicability. Although registration would not guarantee better RWE studies would be conducted, it would encourage the prospective disclosure of study plans, timing, and rationale for modifications. A joint task force of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE) recommended that investigators preregister their RWE studies and post their study protocols in a publicly available forum before starting studies to reduce publication bias and improve the transparency of research methods. Recognizing that published recommendations alone are insufficient, especially without accessible registration options and with no incentives, a group of experts gathered on February 25 and 26, 2019, in National Harbor, Maryland, to explore the structural and practical challenges to the successful implementation of the recommendations of the ISPOR/ISPE task force for preregistration. This positioning article describes a plan for making registration of HETE RWE studies routine. The plan includes specifying the rationale for registering HETE RWE studies, the studies that should be registered, where and when these studies should be registered, how and when analytic deviations from protocols should be reported, how and when to publish results, and incentives to encourage registration. Table1 summarizes the rationale, goals, and potential solutions that increase transparency, in addition to unique concerns about secondary data studies. Definitions of terms used throughout this report are provided in Table2.

Sydney Melancholia Prototype Index (SMPI): translation and cross-cultural adaptation to Brazilian Portuguese.

Introduction Depression is possibly not a single syndrome but rather comprises several subtypes. DSM-5 proposes a melancholia specifier with phenotypic characteristics that could be associated with clinical progression, biological markers or therapeutic response. The Sydney Melancholia Prototype Index (SMPI) is a prototypic scale aimed to improve the diagnosis of melancholia. So far, there is only an English version of the instrument available. The aim of this study is to describe the translation and adaptation of the English version of the SMPI into Brazilian Portuguese.Methods Translation and cross-cultural adaptation of the self-report (SMPI-SR) and clinician-rated (SMPI-CR) versions into Brazilian Portuguese were done following recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). This guideline includes the following steps: preparation, forward translation, reconciliation, back translation, back translation review, harmonization, cognitive debriefing, debriefing results review, proofreading and final report.Results The Brazilian Portuguese versions of the SMPI were well-accepted by respondents. Changes in about two-thirds of the items were considered necessary to obtain the final Brazilian Portuguese version of the SMPI.Conclusions Both versions of the SMPI are now available in Brazilian Portuguese. The instrument could become an important option to enhance studies on melancholia in Portuguese-speaking samples.

Evidence synthesis in pulmonary arterial hypertension: a systematic review and critical appraisal

BackgroundThe clinical landscape of pulmonary arterial hypertension (PAH) has evolved in terms of disease definition and classification, trial designs, available therapies and treatment strategies as well as clinical guidelines. This study critically appraises published evidence synthesis studies, i.e. meta-analyses (MA) and network-meta-analyses (NMA), to better understand their quality, validity and discuss the impact of the findings from these studies on current decision-making in PAH.MethodsA systematic literature review to identify MA/NMA studies considering approved and available therapies for treatment of PAH was conducted. Embase, Medline and the Cochrane’s Database of Systematic Reviews were searched from database inception to April 22, 2020, supplemented by searches in health technology assessment websites. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) checklist covering six domains (relevance, credibility, analysis, reporting quality and transparency, interpretation and conflict of interest) was selected for appraisal of the included MA/NMA studies.ResultsFifty-two full publications (36 MAs, 15 NMAs, and 1 MA/NMA) in PAH met the inclusion criteria. The majority of studies were of low quality, with none of the studies being scored as ‘strong’ across all checklist domains. Key limitations included the lack of a clearly defined, relevant decision problem, shortcomings in assessing and addressing between-study heterogeneity, and an incomplete or misleading interpretation of results.ConclusionsThis is the first critical appraisal of published MA/NMA studies in PAH, suggesting low quality and validity of published evidence synthesis studies in this therapeutic area. Besides the need for direct treatment comparisons assessed in long-term randomized controlled trials, future efforts in evidence synthesis in PAH should improve analysis quality and scrutiny in order to meaningfully address challenges arising from an evolving therapeutic landscape.

Traducción y adaptación transcultural al español, catalán y gallego de la escala Hopkins Symptom Checklist-25 para la detección de depresión en Atención Primaria

AimTo describe the translation and cross-cultural adaptation process of the Hopkins Symptom Checklist-25 (HSCL-25) scale into Spanish, Catalan and Galician. DesignTranslation, cross-cultural adaption and comprehensibility analysis through cognitive debriefing. LocationResearch Units of Primary Care in Barcelona and Vigo. ParticipantsFamily doctors and Primary Care patients. Main measurementsFollowing the guidelines of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR): 1) Direct translation. 2) Pilot study based on Delphi methodology with family doctors. 3) Back-translation. 4) Equivalence analysis. 5) Comprehension analysis of versions obtained in Spanish, Catalan and Galician through cognitive debriefing in a sample of patients. 6) Transcultural harmonization. Results73 family doctors participated in the Delphi study. The consensus was established in the first round for the Spanish and Catalan translations, and in the second round for the Galician. The back-translations were similar in all 3languages. All versions were equivalent between them and compared to the original English version. In the cognitive interview, 10 patients participated for each language, without modifying the writing of the items. ConclusionsThe translations of the HSCL-25 scale in Spanish, Catalan and Galician are semantically and conceptually equivalent to the original version. Translations are understandable and well accepted by patients.

Cross-Cultural Adaptation and Validation of the Arabic Version of Musculoskeletal Health Questionnaire (MSK-HQ-Ar).

Background: Musculoskeletal disorders (MSD) affect millions of people worldwide. Musculoskeletal Health Questionnaire (MSK-HQ) is a valid and reliable tool to assess the health of patients with MSD. However, this scale is not available in the Arabic language. The purpose of this study was to translate and cross-culturally adapt the Musculoskeletal Health Questionnaire (MSK-HQ) into Arabic (MSK-HQ-Ar) and evaluate its validity and reliability among participants with MSD. Methods: This cross-sectional study used guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) to translate as well as validate the psychometric properties of MSK-HQ-Ar. Patients with MSD (n = 149) living in Taif participated in the study. Cronbach’s alpha and the intraclass correlation coefficient (ICC) were used to assess internal consistency and test-retest reliability of MSK-HQ-Ar respectively. Spearman’s correlation was used to assess the correlation between MSK-HQ-Ar and the European quality of life five-dimension, five-level scale (EQ-5D-5L). Results: Out of 149 participants, 119 completed the MSK-HQ-Ar twice. The scale showed good internal consistency, Cronbach’s alpha (0.88), and reliability (ICC 0.92–0.95). A strong association was found with the EQ-5D-5L scores. Conclusion: The adapted MSK-HQ-Arabic version revealed acceptable psychometric properties and is a valid and reliable outcome measure to assess MSK health among Arabic speaking patients with MSD.

Linguistic and content validation of the translated and culturally adapted PG-SGA, as perceived by Norwegian cancer patients and healthcare professionals.

The Scored Patient-Generated Subjective Global Assessment (PG-SGA©) is a validated nutritional screening, assessment, monitoring, and triage tool. When translated to other languages, the questions and answering items need to be conceptually, semantically, and operationally equivalent to the original tool. In this study, we aimed to assess linguistic and content validity of the PG-SGA translated and culturally adapted for the Norwegian setting, as perceived by Norwegian cancer patients and healthcare professionals (HCPs). We have translated and culturally adapted the original PG-SGA for the Norwegian setting, in concordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Cancer patients and HCPs, including nurses, dietitians and physicians, were invited to participate. Comprehensibility and difficulty were assessed by patients for the patient component (PG-SGA Short Form), and by HCPs for the professional component. Content validity was assessed for the full PG-SGA by HCPs only. The data were collected by a questionnaire and evaluations were operationalized by a 4-point scale. Item and scale indices were calculated for comprehensibility (Item CI, Scale CI), difficulty (Item DI, Scale DI) and content validity (Item CVI, Scale CVI). Fifty-one cancer patients and 92 HCPs participated in the study. The patients perceived comprehensibility and difficulty of the Norwegian PG-SGA Short Form as excellent (Scale CI=0.99 and DI=0.97). However, HCPs perceived comprehensibility and difficulty of the professional component as below acceptable (Scale CI=0.78 and DI=0.66), and the physical exam was being rated as the most difficult part (Item DI 0.26 to 0.65). Content validity for the full Norwegian PG-SGA was considered excellent (Scale CVI=0.99) by the HCPs. The patient component of PG-SGA was considered clear and easy to complete, and the full Norwegian PG-SGA was considered as relevant by HCPs. In the final Norwegian PG-SGA, changes have been made to improve comprehensibility of the professional component. To improve perceived difficulty of completing the professional component, training of professionals is indicated.

Marginal Health Care Expenditure Burden Among U.S. Civilian Noninstitutionalized Individuals with Multiple Sclerosis: 2010-2015.

Multiple sclerosis (MS) is a chronic neuroinflammatory disorder with significant health care burden. However, little is known about health care expenditures since the introduction of oral agents for MS after 2010. To analyze health care expenditures in individuals with MS using Medical Expenditure Panel Survey (MEPS) data from 2010-2015. This retrospective cross-sectional study included adults (≥ 18 years) with MS (Clinical Classification Code 080) and those without MS based on the 2010-2015 full year consolidated MEPS Household Component and Medical Provider Component data files. Descriptive weighted analyses were performed to compare health care expenditures between individuals with MS and without MS. The 2-part model involving probit and generalized linear models was used to estimate the marginal increase in total health care expenditures for MS patients. There were 0.61 million patients (95% CI = 0.50-0.72) diagnosed with MS annually, accounting for a prevalence of 0.25%. The 2-part model revealed that the marginal total health care expenditures in patients diagnosed with MS were $20,103.49 (95% CI = $14,516.24-$25,690.73) more compared with those without MS. Further, the mean adjusted prescription medication expenditures for the MS group were $13,092.16 (95% CI = $9,452.20-$16,732.12) higher than the non-MS group and accounted for 65.12% of total health care expenditures in MS. MS is an expensive neuroinflammatory disease with a majority of the burden attributable to prescription medications. High prescription expenditure burden can be a barrier to optimal patient care in MS. No funding was received for this study. Hutton reports grants from Adamas, Biogen, EMD Serono, Genzyme, Hoffman-LaRoche, MedImmune, Mallinckrodt, and Novartis and fees from Biogen, Celgene, Genzyme, Genentech, and Novartis, outside the submitted work. Aparasu reports grants from Novartis, Incyte, and Astellas, outside the submitted work. Earla and Thornton have nothing to disclose. Part of the study findings was presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2019 National Conference; May 18-22, 2019; New Orleans, LA.

Development of the symptoms and impacts questionnaire for Crohn's disease and ulcerative colitis.

SummaryBackgroundPatient‐reported outcome (PRO) measures historically used in inflammatory bowel disease have been considered inadequate to support future drug labelling claims by regulatory agencies.AimsTo develop PRO tools for use in Crohn's disease (CD) and ulcerative colitis (UC) following guidance issued by the US FDA and the ISPOR (International Society for Pharmacoeconomics and Outcomes Research).MethodsConcept elicitation and cognitive interviews were conducted in adult patients (≥18 years) across the United States and Canada. Semi‐structured interview guides were used to collect data, and interview transcripts were coded and analysed. Concept elicitation results were considered alongside existing literature and clinical expert opinion to identify candidate PRO items. Cognitive interviews evaluated concept relevance, interpretability and structure, and facilitated instrument refinement. Concept elicitation participants, except those with an ostomy, underwent centrally read endoscopy to assess inflammatory status.ResultsIn all, 54 participants (mean age: 46.2 years; 66.7% female) were included in the CD concept elicitation interviews. In total, 80 symptom concepts and 61 impact concepts were identified. After three waves of cognitive interviews, the 31‐item Symptoms and Impacts Questionnaire for CD (SIQ‐CD) was developed. In the UC concept elicitation phase, 53 participants were interviewed (mean age: 41.4 years; 49.1% female). In total, 79 symptoms concepts and 49 impact concepts were identified. Following two waves of cognitive interviews, the 29‐item Symptoms and Impacts Questionnaire for UC (SIQ‐UC) was developed. Both instruments include four symptom and six impact domains.ConclusionsWe developed PROs to support CD and UC drug labelling claims. Psychometric validation studies to evaluate instrument reliability and responsiveness are ongoing.

Patients’ involvement in the development of pharmaceutical products at pre-launch: problems experienced and how to resolve them

Background: Pharmaceutical products are developed for patients as the end-users. It has been advocated that patients should be involved in the development of such products. However, this is not the case as patients are usually not involved. To date, no study has investigated the involvement of patients at pre-launch stage of pharmaceutical products. Therefore, this study explored patients’ involvement at this stage of pharmaceutical products development. Methods: A survey of Market Access (MA) and Health Economic and Outcomes Research (HEOR) professionals at International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Glasgow 2017 was carried out. Responses were examined using thematic and descriptive analyses to capture professionals’ suggestions about involvement of patients at pre –launch stage and how to resolve issues identified. Results: Results showed patients are not currently involved in this process, depriving them of benefits associated with involvement such as improved psychological well-being, health outcomes and drug safety. Participants advocated involvement of patients in the developments of pharmaceutical products. This may help improve adherence and quality of life in patients hence, ensuring effective use of pharmaceutical products. Conclusion: Patients are to be involved at pre-launch stage of pharmaceutical product development. Their involvement can ensure adherence to early stage development regulations. This may facilitate effective networking among stakeholders. Whilst it is generally agreed that patients should be involved to ensure adherence to regulations, problems are experienced that could be resolved by effective communication; understanding of external issues and how to tackle them. Also, it may help with deeper understanding of issues important to patients.