Search

Introduction Mixed treatment comparisons (MTCs) are increasingly important in the assessment of the benefit-risk profile of pharmaceutical treatments for relapsing-remitting multiple sclerosis (RRMS). Interpretation of MTCs requires a clear understanding of the methods of analysis and population studied. The objectives of this work were to compare MTCs of pharmaceutical treatments for RRMS, including a detailed description of differences in populations, treatments assessed, methods used and findings; and to discuss key considerations when conducting an MTC. Methods Fourteen databases were searched until July 2019 to identify MTCs (published during or after 2010) in adults (at least 18 years of age) with RRMS or rapidly evolving severe RRMS treated with any form of pharmaceutical treatment. No language restriction was imposed. Results Twenty-seven MTCs assessing 21 treatments were identified. Comparison highlighted many differences in conduct and reporting between MTCs relating to the patient populations or treatments included, duration of follow-up and outcomes of interest measured. The lack of similarity between the MTCs leads to questions about variability in the robustness of analyses and makes comparisons between studies challenging. Conclusion Given the importance of MTCs for healthcare decision-making, it is imperative that reporting of methods, results and assumptions is clear and transparent to allow accurate interpretation of findings. For MTCs to be relevant, the choice of outcome measures should reflect clinical practice. Combination of treatments or of outcomes measured at different points of time should be avoided, as should imputation without justification. Furthermore, all approved treatment options should be included and updates of MTCs should be conducted when data for new treatments are published.

Background Since 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. Objectives The 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. Methods Searches 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. Results In 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. Conclusions Meta-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 Material The online version of this article (10.1007/s40120-020-00212-5) contains supplementary material, which is available to authorized users.

Background Since 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. Objectives The 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. Methods Searches 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. Results In 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. Conclusions Meta-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.

Introduction Mixed treatment comparisons (MTCs) are increasingly important in the assessment of the benefit–risk profile of pharmaceutical treatments for relapsing–remitting multiple sclerosis (RRMS). Interpretation of MTCs requires a clear understanding of the methods of analysis and population studied. The objectives of this work were to compare MTCs of pharmaceutical treatments for RRMS, including a detailed description of differences in populations, treatments assessed, methods used and findings; and to discuss key considerations when conducting an MTC. Methods Fourteen databases were searched until July 2019 to identify MTCs (published during or after 2010) in adults (at least 18 years of age) with RRMS or rapidly evolving severe RRMS treated with any form of pharmaceutical treatment. No language restriction was imposed. Results Twenty-seven MTCs assessing 21 treatments were identified. Comparison highlighted many differences in conduct and reporting between MTCs relating to the patient populations or treatments included, duration of follow-up and outcomes of interest measured. The lack of similarity between the MTCs leads to questions about variability in the robustness of analyses and makes comparisons between studies challenging. Conclusion Given the importance of MTCs for healthcare decision-making, it is imperative that reporting of methods, results and assumptions is clear and transparent to allow accurate interpretation of findings. For MTCs to be relevant, the choice of outcome measures should reflect clinical practice. Combination of treatments or of outcomes measured at different points of time should be avoided, as should imputation without justification. Furthermore, all approved treatment options should be included and updates of MTCs should be conducted when data for new treatments are published. Electronic Supplementary Material The online version of this article (10.1007/s40120-020-00213-4) contains supplementary material, which is available to authorized users.

Funder: Health Services and Delivery Research Programme; FundRef: https://doi.org/10.13039/501100002001, Guided by the principles of conversation analysis, we examined the communication practices used to negotiate levels of participation in cancer multidisciplinary team meetings and their implications for patient safety. Three cancer teams participated. Thirty-six weekly meetings were video recorded, encompassing 822 case reviews. A cross-section was transcribed using Jefferson notation. We found a low frequency of gaps between speakers (3%), high frequency of overlaps (24%), and no-gaps-no-overlaps (73%), suggesting fast turn transitions. Securing a turn to speak is challenging due to a systematic reduction in turn-taking opportunities. We contribute to group research with the development of a microlevel methodology for studying multidisciplinary teams.

Objectives.To estimate the preferences of osteoporotic patients for medication attributes, and analysedata from seven European countries.Methods.A discrete choice experiment was conducted in Belgium, France, Ireland, the Netherlands,Spain, Switzerland and the UK. Patients were asked to choose repeatedly between two hypotheticalunlabelled drug treatments (and an opt-out option) that varied with respect to four attributes: efficacy inreducing the risk of fracture, type of potential common side effects, and mode and frequency of admin-istration. In those countries in which patients contribute to the cost of their treatment directly, a fifthattribute was added: out-of-pocket cost. A mixed logit panel model was used to estimate patients’preferences.Results.In total, 1124 patients completed the experiment, with a sample of between 98 and 257 patientsper country. In all countries, patients preferred treatment with higher effectiveness, and 6-monthly subcuta-neous injection was always preferred over weekly oral tablets. In five countries, patients also preferred amonthly oral tablet and yearly i.v. injections over weekly oral tablets. In the three countries where the out-of-pocket cost was included as an attribute, lower costs significantly contributed to the treatment preference.Between countries, there were statistically significant differences for 13 out of 42 attribute/level interactions.Conclusion.We found statistically significant differences in patients’ preferences for anti-osteoporosismedications between countries, especially for the mode of administration. Our findings emphasized thatinternational treatment recommendations should allow for local adaptation, and that understanding individ-ual preferences is important if we want to improve the quality of clinical care for patients with osteoporosis.

Introduction: Patient centred care is often at odds with disease-focused evidence-based clinical practice, particularly for patients with multiple chronic conditions (CCs). To assess the extent to which care for patients with multimorbidity was not guideline-concordant and the reasons why not, examining reasons stratified by disease. Methods: Retrospective cohort study conducted within the context of a nurse-primary care physician team-based care management program, the Comprehensive Care for Multimorbid Adults Project (CC-MAP) across 12 primary care clinics in Israel. This study included CC-MAP patients aged 45+ years who had at least two of eight common CCs. Forty-four guideline-based care processes for these eight CCs and dyslipidemia (‘focus conditions’) were evaluated over one year prior to data collection, through EHR review, including: lifestyle modifications, diagnostic and follow-up tests, medications, non-medication treatments, and specialist referrals. When care was not guideline-concordant, reasons why not were examined by: biomedical, personal and care burden, and system related factors. Proportions of non-guideline-concordant care and related reasons were assessed overall and stratified by focus condition. Reasons were also stratified: provider-driven if the clinician didn’t refer care, and patient-driven if care was referred but not followed by the patient. Results: 4515 care processes were evaluated among 204 multimorbid patients, on average aged 72.3 years (SD 9.7) and with 3.8 (SD 1.1) CCs. Overall, 20.8% of care was not guideline-concordant, and when examining disease-specific care for the focus conditions, ranged from 14.7% (for IHD) to 48.9% (for depression). Of 1071 reasons why care deviated from guidelines, 59.8% were provider-driven and 40.2% patient-driven. Thirty-five percent of all reasons given were biomedical-related, 28.5% personal and care burden-related, 13.3% system-related, 11.9% other and 11.9% unknown. A higher proportion of reasons were provider-driven than patient-driven for atrial fibrillation, congestive heart failure, diabetes, and hypertension specific care; whereas, a higher proportion of reasons were patient-driven than provider-driven for chronic kidney disease, chronic obstructive pulmonary disease, depression, and dyslipidemia. For ischemic heart disease, the provider- and patient-driven reasons were fairly evenly divided. Discussion: Patients with multimorbidity do not receive about a fifth of guideline recommended care overall, but this proportion varies substantially across diseases. More than a third of non-guideline-concordant care is driven by biomedical reasons, and about a third attributed to patient-related reasons. Conclusions: Understanding the drivers to deviations from guidelines can inform improvements to guidelines and care delivery for patients with multimorbidity. Lessons learned: These findings show that many clinical, personal patient, and system-related reasons exist for deviation from guidelines. Quantifying these types of reasons may provide a basis for tailoring assessments of the appropriateness and compatibility in combining disease-specific guidelines for multimorbid patients. Limitations: An evaluation in a control group or in a usual care setting was not possible for this study and while the extent of guideline-concordance was measured, this was not linked to outcomes. Suggestions for future research: Future research could examine these patterns of care in a usual care practice setting, as well as aim to evaluate the relationship of guideline-concordant care with clinical outcomes among multimorbid patients.

Background: Patient preferences (PP), which are investigated in PP studies using qualitative or quantitative methods, are a growing area of interest to the following stakeholders involved in the medical product lifecycle: academics, health technology assessment bodies, payers, industry, patients, physicians, and regulators. However, the use of PP in decisions along the medical product lifecycle remains limited. As the adoption of PP heavily relies on these stakeholders, knowledge of their perceptions of PP is critical. Objective: This study aimed to characterize stakeholders’ attitudes, needs, and concerns with respect to PP in decision making along the medical product lifecycle. Methods: Semi-structured interviews (n = 143) were conducted with academics (n = 24), health technology assessment/payer representatives (n = 24), industry representatives (n = 24), patients, caregivers and patient representatives (n = 24), physicians (n = 24), and regulators (n = 23) from seven European countries and the USA. Interviews were conducted between April and August 2017. The framework method was used to organize the data and identify themes and key findings in each interviewed stakeholder group. Results: Interviewees reported being unfamiliar (43%), moderately familiar (42%), or very familiar (15%) with preference methods and studies. Interviewees across stakeholder groups generally supported the idea of using PP in the medical product lifecycle but expressed mixed opinions about the feasibility and impact of using PP in decision making. Interviewees from all stakeholder groups stressed the importance of increasing stakeholders’ understanding of the concept of PP and preference methods and ensuring patients’ understanding of the questions asked in PP studies. Key concerns and needs in each interviewed stakeholder group were as follows: (1) academics: investigating the validity, reliability, reproducibility, and generalizability of preference methods; (2) health technology assessment/payer representatives: developing quality criteria for evaluating PP studies and gaining insights into how to weigh them in reimbursement/payer decision making; (3) industry representatives: obtaining guidance on PP studies and recognition on the importance of PP from decision makers; (4) patients, caregivers, and patient representatives: providing an incentive and adequate information towards patients when participating in PP studies; (5) physicians: avoiding bias as a result of commercial agendas in PP studies and clarifying how to deal with subjective and emotional elements when measuring PP; and (6) regulators: avoiding the misuse of PP study results to overrule the traditional efficacy and safety criteria used for marketing authorization and obtaining robust PP study results. Conclusions: Despite the interest all interviewed stakeholder groups reported in PP, the effective use of PP in decision making across the medical product lifecycle is currently hampered by a lack of standardization and consensus on how to both measure and use PP., SCOPUS: ar.j, info:eu-repo/semantics/published

Contains fulltext : 200589.pdf (Publisher’s version ) (Closed access) BACKGROUND: Lung cancer screening can reduce cancer mortality. Most implementation studies focus only on low-dose computed tomography (LDCT) and clinical attributes of screening and do not include preferences of potential participants. In this study we evaluated the perceived value of screening programs based on LDCT, breath analysis (BA), or blood biomarkers (BB) according to the perspective of the target population. METHODS: A multi-criteria decision analysis framework was adopted. The weights of seven attributes of screening (sensitivity, specificity, radiation burden, duration of screening process, waiting time until results are communicated, location of screening, and mode of screening) were obtained from an earlier study that included a broad sample from the Netherlands. Performance data for the screening modalities was obtained from clinical trials and expert opinion. Parameter uncertainty about clinical performances was incorporated probabilistically, while heterogeneity in preferences was analyzed through subgroup analyses. RESULTS: The mean overall values were 0.58 (CI: 0.57 to 0.59), 0.57 (CI: 0.56 to 0.59), and 0.44 (CI: 0.43 to 0.45) for BB, BA, and LDCT, respectively. Seventy-seven per cent of respondents preferred BB or BA. For most subgroups, the overall values were similar to those of the entire sample. BA had the highest value for respondents who would have been eligible for earlier screening trials. DISCUSSION: BB and BA seem valuable to participants because they can be applied in a primary care setting. Although LDCT still seems preferable given its strong and positive evidence base, it is important to take non-clinical attributes into account to maximize attendance.

Objectives: Several studies have reported multiple barriers to and facilitators for the uptake of health technology assessment (HTA) information by policy makers. This study elicited, using best-worst scaling (BWS), the most important barriers and facilitators and their relative weight in the use of HTA by policy makers.Methods: Two BWS object case surveys (one for barriers, one for facilitators) were conducted among sixteen policy makers and thirty-three HTA experts in the Netherlands. A list of twenty-two barriers and nineteen facilitators was included. In each choice task, participants were asked to choose the most important and the least important barrier/facilitator from a set of five. We used Hierarchical Bayes modeling to generate the mean relative importance score (RIS) for each factor and a subgroup analysis was conducted to assess differences between policy makers and HTA experts.Results: The five most important barriers (RIS > 6.00) were “no explicit framework for decision-making process,” “insufficient support by stakeholders,” “lack of support,” “limited generalizability,” and “absence of appropriate incentives.” The six most important facilitators were: “availability of explicit framework for decision making,” “sufficient support by stakeholders,” “appropriate incentives,” “sufficient quality,” “sufficient awareness,” and “sufficient support within the organization.” Overall, perceptions did not differ markedly between policy makers and HTA experts.Conclusions: Our study suggests that barriers and facilitators related to “policy characteristics” and “organization and resources” were particularly important. It is important to stimulate a pulse at the national level to create an explicit framework for including HTA in the decision-making context.

Background Network meta-analysis (NMA) has become a popular method to compare more than two treatments. This scoping review aimed to explore the characteristics and methodological quality of knowledge synthesis approaches underlying the NMA process. We also aimed to assess the statistical methods applied using the Analysis subdomain of the ISPOR checklist. Methods Comprehensive literature searches were conducted in MEDLINE, PubMed, EMBASE, and Cochrane Database of Systematic Reviews from inception until April 14, 2015. References of relevant reviews were scanned. Eligible studies compared at least four different interventions from randomised controlled trials with an appropriate NMA approach. Two reviewers independently performed study selection and data abstraction of included articles. All discrepancies between reviewers were resolved by a third reviewer. Data analysis involved quantitative (frequencies) and qualitative (content analysis) methods. Quality was evaluated using the AMSTAR tool for the conduct of knowledge synthesis and the ISPOR tool for statistical analysis. Results After screening 3538 citations and 877 full-text papers, 456 NMAs were included. These were published between 1997 and 2015, with 95% published after 2006. Most were conducted in Europe (51%) or North America (31%), and approximately one-third reported public sources of funding. Overall, 84% searched two or more electronic databases, 62% searched for grey literature, 58% performed duplicate study selection and data abstraction (independently), and 62% assessed risk of bias. Seventy-eight (17%) NMAs relied on previously conducted systematic reviews to obtain studies for inclusion in their NMA. Based on the AMSTAR tool, almost half of the NMAs incorporated quality appraisal results to formulate conclusions, 36% assessed publication bias, and 16% reported the source of funding. Based on the ISPOR tool, half of the NMAs did not report if an assessment for consistency was conducted or whether they accounted for inconsistency when present. Only 13% reported heterogeneity assumptions for the random-effects model. Conclusions The knowledge synthesis methods and analytical process for NMAs are poorly reported and need improvement. Electronic supplementary material The online version of this article (doi:10.1186/s12916-016-0764-6) contains supplementary material, which is available to authorized users.

Multiple pregnancies lead to complications and induce high costs. The most successful way to decrease multiple pregnancies in IVF is to transfer only one embryo, which might reduce the efficacy of treatment. The objective of this review is to determine which embryo-transfer policy is most cost-effective: elective single-embryo transfer (eSET) or double-embryo transfer (DET). Several databases were searched for (cost* or econ*) and (single embryo* or double embryo* or one embryo* or two embryo* or elect* embryo or multip* embryo*). On the basis of five exclusion criteria, titles and abstracts were screened by two individual reviewers. The remaining papers were read for further selection, and data were extracted from the selected studies. A total of 496 titles were identified through the searches and resulted in the selection of one observational study and three randomized studies. Study characteristics, total costs and probability of live births were extracted. Besides this, cost-effectiveness and incremental cost-effectiveness were derived. It can be concluded that DET is the most expensive strategy. DET is also most effective if performed in one fresh cycle. eSET is only preferred from a cost-effectiveness point of view when performed in good prognosis patients and when frozen/thawed cycles are included. If frozen/thawed cycles are excluded, the choice between eSET and DET depends on how much society is willing to pay for one extra successful pregnancy.

Multiple pregnancies lead to complications and induce high costs. The most successful way to decrease multiple pregnancies in IVF is to transfer only one embryo, which might reduce the efficacy of treatment. The objective of this review is to determine which embryo-transfer policy is most cost-effective: elective single-embryo transfer (eSET) or double-embryo transfer (DET). Several databases were searched for (cost* or econ*) and (single embryo* or double embryo* or one embryo* or two embryo* or elect* embryo or multip* embryo*). On the basis of five exclusion criteria, titles and abstracts were screened by two individual reviewers. The remaining papers were read for further selection, and data were extracted from the selected studies. A total of 496 titles were identified through the searches and resulted in the selection of one observational study and three randomized studies. Study characteristics, total costs and probability of live births were extracted. Besides this, cost-effectiveness and incremental cost-effectiveness were derived. It can be concluded that DET is the most expensive strategy. DET is also most effective if performed in one fresh cycle. eSET is only preferred from a cost-effectiveness point of view when performed in good prognosis patients and when frozen/thawed cycles are included. If frozen/thawed cycles are excluded, the choice between eSET and DET depends on how much society is willing to pay for one extra successful pregnancy.

Network meta-analysis (NMA), combining direct and indirect comparisons, is increasingly being used to examine the comparative effectiveness of medical interventions. Minimal guidance exists on how to rate the quality of evidence supporting treatment effect estimates obtained from NMA. We present a four-step approach to rate the quality of evidence in each of the direct, indirect, and NMA estimates based on methods developed by the GRADE working group. Using an example of a published NMA, we show that the quality of evidence supporting NMA estimates varies from high to very low across comparisons, and that quality ratings given to a whole network are uninformative and likely to mislead.

Introduction: Patients have the right to influence the care they receive, but their wish to participate in care decision-making is unclear. Aim: This study investigates whether participation in nursing documentation influences patient participation in care decision-making, mastery, self-esteem, empowerment and depressive feelings among adult in-patients with chronic disease. Materials and Methodology: Adult patients (n=39) with chronic diseases were randomized. The intervention group participated in nursing documentation. Upon departure, patients filled in questionnaires about participation in care decision-making, mastery, self-esteem, empowerment and depressive feelings. Results: The majority of the patients preferred a collaborative or passive role regarding care decision-making. Lack of knowledge was one reason for non-participation. Having been diagnosed more than five years previously meant stronger empowerment. Conclusion: It is a challenge for nurses to find strategies to assess patients’ wishes regarding participation in care decision-making. Nurses must support patients’ knowledge of their disease and empowerment.