Publication bias has the potential to adversely impact clinical decision making and patient health if alternative decisions would have been made had there been complete publication of evidence.

The objective of our analysis was to determine if earlier publication of the complete evidence on rosiglitazone’s risk of myocardial infarction (MI) would have changed clinical decision making at an earlier point in time. We tested several methods for adjustment of publication bias to assess the impact of potential time delays to identifying the MI effect. We then performed a cumulative meta-analysis (CMA) for both published studies (published-only data set) and all studies performed (comprehensive data set). We then created an adjusted data set using existing methods of adjustment for publication bias (Harbord regression, Peter’s regression, and the nonparametric trim and fill method) applied to the limited data set. Finally, we compared the time to the decision threshold for each data set using CMA.

Although published-only and comprehensive data sets did not provide notably different final summary estimates [OR = 1.4 (95 percent confidence interval [CI]: .95–2.05) and 1.42 (95 percent CI: 1.03–1.97)], the comprehensive data set reached the decision threshold 36 months earlier than the published-only data set. All three adjustment methods tested did not show a differential time to decision threshold versus the published-only data set.

Complete access to studies capturing MI risk for rosiglitazone would have led to the evidence reaching a clinically meaningful decision threshold 3 years earlier.

To undertake a technical review of the search interface of the ISPOR Presentations Database. By technical review, we mean an evaluation of the technical aspects of the search interface and functionality, which a user must navigate to complete a search.

A validated checklist (Bethel and Rogers, 2014, Health Info Libr J, 31, 43-53) was used to identify where the interface performed well, where the interface was adequate, where the interface performed poorly, where functionality available in core biomedical bibliographic databases does not exist in the ISPOR database, and to establish a list of any issues arising during the review. Two researchers independently undertook the technical review in October 2021.

The ISPOR database scored 35 of a possible 165 (27/111 essential criteria and 8/54 desirable criteria). Two issues arising were identified, both of which will cause searchers to miss potentially eligible abstracts: (i) that search terms, which include * or ? as truncation or wildcard symbols should not be capitalized (e.g., cost* not Cost*; organi?ation not Organi?ation) and (ii) that quotation marks should be straight sided in phrase searching (e.g., “cost analyses” not “cost analyses”).

The ISPOR database is a promising and free database to identify abstracts/posters presented at ISPOR. We summarize two key issues arising, and we set out proposed changes to the search interface, including: adding the ability to export abstracts to a bibliographic tool, exporting search strategies, adding a researcher account, and updating the help guide. All suggestions will further improve this helpful database.

Patients with hematological malignancies are likely to develop hypogammaglobulinemia (HGG) and subsequent infections. Immunoglobulin (Ig) replacement is commonly given to prevent infections, but the total costs and cost effectiveness of its use are unknown.

A systematic review was conducted following PRISMA guidelines to assess evidence on the costs and cost effectiveness of Ig replacement, administered intravenously (IVIg) or subcutaneously (SCIg), in adult patients with hematological malignancies. This review was registered with PROSPERO (CRD42022321908).

Six studies were included out of a total of 3,612 citations. A narrative synthesis was conducted because of the high level of heterogeneity across the included studies. Two economic evaluations were identified: one cost-utility analysis (CUA) of IVIg versus no Ig and one comparing IVIg with SCIg. The quality of the evidence was low, with most studies having small patient numbers and a high risk of bias. Compared with no treatment, Ig replacement reduced the hospitalization rate in patients with hematological malignancies.

One study reported no change in hospitalization rates following a program to reduce IVIg use, and an observational study comparing IVIg with SCIg found more hospitalizations with SCIg but lower total costs per patient. The CUA comparing IVIg with no IVIg suggested that IVIg treatment was not cost effective, but this study was published in 1991 and had significant limitations. The other CUA found that home-based SCIg was more cost effective than IVIg, but model inputs were derived from unpublished data in a very small patient cohort with HGG and different malignancies.

Our review highlights key gaps in the literature. The cost effectiveness of Ig replacement in patients with hematological malignancies is still very uncertain. Despite the increasing use of Ig replacement there are limited data regarding its direct and indirect costs, and its optimal use and implications for healthcare resources remain unclear. Given the paucity of data on the cost and cost effectiveness of Ig treatment in this population, further health economic research is warranted.

The Canadian BIA guideline was published by the Patented Medicine Prices Review Board (PMPRB) in 2007. Our initial systematic literature review of national and international BIA guidelines showed that a number of new recommendations relating to BIA model structure, input data and reporting format have been adopted in other jurisdictions such as UK, Australia, Poland, Ireland, Belgium, France and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). The main objective of the present study was to conduct a comparative review of national, international and Canadian Federal, provincial and territorial BIA guidelines and provide a list of new recommendations related to the BIA key elements which have not been discussed or included in the Canadian PMPRB BIA guidelines.

BIAs guidelines were searched in databases such as MEDLINE, EMBASE, Cochrane, and the gray literature including regulatory agency websites. An Excel-based data abstraction form was designed in order to highlight differences between recommendations related to the BIA key elements provided by PMPRB, provincial, and other national and international BIA guidelines.

Twelve guidelines were reviewed in detail. Sixty percent of the recommendations were new or were different from recommendations in the Canadian PMPRB BIA guidelines. They related to BIA key elements such as perspective, target population, costing, presenting results, data sources and handling the uncertainty.

The present literature review is the initial step towards updating the Canadian BIA guidelines. This study presents a comparative review of key elements in BIA among different guidelines and provides a list of relevant practical recommendations for the improvement of the Canadian BIA guidelines. The new methodologic advancements and recommendations that were identified are being presented to Canadian stakeholders for their opinion and feedback prior to the development of a proposed new set of Canadian guidelines.

The Scottish Medicines Consortium (SMC) provides advice on which new medicines should be accepted for routine use by the NHS in Scotland. To help increase the accessibility of the advice, SMC produces public information summaries, which have been published on the SMC website since 2018. We conducted an evaluation to investigate if the public summaries are achieving their purpose and subsequently help inform improvements from a user perspective. The objectives were to determine how the public summaries are being used; what users like and what could be improved; and if they have achieved a greater understanding of decisions.

The first stage of the evaluation involved surveying patient groups (organizations that represent the interests of patients, families and carers) to investigate how they use the public summaries. We then conducted workshops with patient groups and Public Partners (members of the public that volunteer with Healthcare Improvement Scotland) to gather perspectives on the content, language and layout of a selection of public summaries.

The survey responses (n = 14) illustrate that the public summaries are being used in a variety of ways. The majority (n = 10) of patient groups reported using the public summaries to help explain SMC decisions to the people they support.

The workshops highlighted that participants found the public summaries clear and helpful. In general, patient groups felt the level of detail and language used in the public summaries improved their understanding of SMC decisions compared to other sources of information, such as the press release or Detailed Advice Document.

There were a number of suggested improvements, including changing the layout (so the SMC decision appears first) and providing definitions for some technical terms. Where actionable, these recommendations have been implemented.

Working in partnership with patient groups and Public Partners has enabled SMC to further strengthen public summaries, and patient engagement more broadly. Improvements have ensured that SMC's decisions are communicated clearly, helping to increase accessibility.

Spain incorporated in 2020 changes in its health technology assessment (HTA), pricing, and reimbursement system for medicines including publishing reports, development of networks of experts, or consultation with stakeholders. Despite these changes, it is unclear how deliberative frameworks are applied and the process has been criticized for not being sufficiently transparent. This study analyses the level of implementation of deliberative processes in HTA for medicines in Spain.

We review the grey literature and summarize the Spanish HTA, pricing, and reimbursement process of medicines. We apply the deliberative processes for HTA checklist, developed to assess the overall context of the deliberative process, and identify the stakeholders involved and type of involvement following the framework for evidence-informed deliberative processes, a framework for benefit package design that aims to optimize the legitimacy of decision making.

In the Spanish HTA, pricing, and reimbursement process deliberation takes place in order to exchange viewpoints and reach common ground, mainly during the prioritization, assessment, and appraisal steps. It is closed to the public, not clearly summarized in published documents and limited to the Ministry of Health, the regulatory agency, other Ministries, and experts with mostly clinical and/or pharmaceutical background. The views of stakeholders are only represented through consultation. Communication is the most commonly used form of stakeholder engagement.

Despite improvements in transparency of the Spanish HTA process for evaluating medicines, aspects related to stakeholder involvement and implementation of deliberative frameworks need further attention in order to achieve further legitimacy of the process.

A gap exists between the evidence for reducing risk of knee osteoarthritis (KOA) progression and its application in patients’ daily lives. We aimed to bridge this gap by identifying patient and family physician (FP) self-management priorities to conceptualize and develop a mobile-health application (m-health app). Our co-design approach combined priorities and concerns solicited from patients and FPs with evidence on risk of progression to design and develop a KOA self-management tool.

Parallel qualitative research of patient and FP perspectives was conducted to inform the co-design process. Researchers from the Enhancing Alberta Primary Care Research Networks (EnACT) evaluated the mental models of FPs using cognitive task analysis through structured interviews with four FPs. Using grounded theory methods, patient researchers from the Patient and Community Engagement Research (PaCER) program interviewed five patients to explore their perspectives about needs and interactions within primary care. In three co-design sessions relevant stakeholders (four patients, five FPs, and thirteen researchers) participated to: (i) identify user needs with regard to KOA self-management; and (ii) conceptualize and determine design priorities and functionalities of an m-health app using a modified nominal group process.

Priority measures for symptoms, activities, and quality of life from the user perspective were determined in the first two sessions. The third co-design session with our industry partner resulted in finalization of priorities through interactive patient and FP feedback. The top three features were: (i) a symptoms graph and summary; (ii) information and strategies; and (iii) setting goals. These features were used to inform the development of a minimum viable product.

The novel use of co-design created directive dialog around the needs of patients, highlighting the contrasting views that exist between patients and FPs and emphasizing how exploring these differences might lead to strong design options for patient-oriented m-health apps. Characterizing these disjunctions has important implications for operationalizing patient-centered health care.

Digital medication health service (DMHS) platforms are increasingly used by pharmaceutical companies to provide direct medication health services through digital methods like apps, hotlines, and web services, etcetera. However, the implications of such platforms in supporting health technology assessment (HTA) are rarely discussed in the literature. This presentation sets out the opportunities for using the DMHS platforms of pharmaceutical companies as real-world data sources for HTA.

A mixed-method qualitative study combining literature review and case study was conducted. Relevant literature was identified by searching the Web of Science and PubMed databases. A case study on current DMHS platforms in China was carried out using an inductive approach to identify the key elements emerging from these platforms.

DMHS platforms of pharmaceutical companies can identify multiple attributes of medication information needs regarding medical products, including effectiveness, safety, and economic factors. The platforms can respond to different stakeholders, including patients and their carers, doctors, nurses, pharmacists, etcetera. As one kind of interactive process, DMHS platforms can provide further services, including patient education, consultation, and evaluation, follow-up visits, chronic disease management, promotion of the rational use of drugs, therapeutic drug monitoring, and adverse drug reaction surveillance and reporting.

The DMHS platforms of pharmaceutical companies provide a unique and valuable real-world data source for HTA. These types of self-reported outcomes have not gained enough attention in HTA. Collective efforts by HTA agencies and pharmaceutical companies are needed to set strategies for integrating DMHS platforms into HTA.

Limited public money is available for funding research and the majority of clinical research undertaken is funded by industry. Mechanisms to regulate conflicts of interest within the research process have been implemented. However, these policies by themselves do not protect against potential sponsorship bias that would affect research results to inform decision makers when using the results of these trials. Therefore, the main aim of this study was to evaluate the influence of sponsorship bias on the treatment effects of RCTs.

This was a meta-epidemiological study. A random sample of RCTs included in meta-analyses of physical therapy (PT) area were identified. Data extraction including assessments of appropriate influence of funders was conducted independently by two reviewers. To determine the association between biases related to sponsorship biases and effect sizes, a two-level analysis was conducted using a meta-meta-analytic approach.

We analysed 393 trials included in forty-three meta-analyses. The most common sources of sponsorship for this sample of PT trials were government (n = 205, 52.16 percent) followed by academic (n = 44, 11.2 percent), and industry (n = 39, 10 percent). The funding was not declared in a high percentage of the trials (n = 85, 22 percent). The influence of the trial sponsor was assessed as being appropriate in 246 trials (63 percent) and considered inappropriate/unclear in 147 (37 percent) of them. There was a significant difference in effects estimates between trials with appropriate and inappropriate influence of funders (ES= 0.15; 95% CI -0.03, 0.33;). Trials with inappropriate/unclear influence of funders tended to have on average a larger effect size than those with appropriate influence of funding

Treatment effect size estimates were 0.15 larger in trials with lack of appropriate influence of funders. Systematic reviewers should perform sensitivity analyses based on appropriateness of influence of sponsorship in included trials.

Horizon scanning for health technology appraisal (HTA) in England involves topic notification to the National Institute for Health and Care Excellence (NICE) via technology briefings. This activity is undertaken by the Innovation Observatory with submission timelines designed to ensure that HTA decisions align with regulatory approval time. In this paper, we aimed to track and assess the progression and current status of the topics notified for HTA and provide a descriptive analysis of these topics.

Technology briefings were mapped from submission to NICE technology appraisal/highly specialized technologies recommendations from April 2017 until October 2021. This was done using a combination of searches on Google and NICE website, searching a downloadable spreadsheet containing NICE topic selection decisions, and querying NICE Topic Selection team. Analysis was undertaken regarding type of indications and interventions of submitted topics and published guidance.

Six-hundred and ninety-three topics entered the NICE scoping process, of which 94 percent were prioritized. As of November 2021, approximately 39 percent of prioritized topics were in scoping/in progress, 31 percent were proposed/completed, 20 percent were suspended/terminated, and 4 percent were referred back to Innovation Observatory (IO) for further monitoring.

Our work demonstrates that horizon scanning for HTA is a complex and time-intensive process. Timelines and progress through HTA is challenging due to the growing number of innovative medicines, significant uncertainties, and limited transparency in clinical development and regulatory pathways. A better understanding of clinical trials and regulatory requirements may help eliminate some of this uncertainty and improve timely HTA.

To assess convergent validity of stated preference methods in studies where they were used to elicit patient preferences for informing medical product decisions.

In four studies, two stated preference methods were used to elicit preferences of patients with neuromuscular diseases (NMD; n = 140, Discrete Choice Experiment [DCE] and Best-Worst Scaling [BWS] case 2), diabetes (n = 495, DCE and swing weighting [SW]), myocardial infarction (MI; n = 335, DCE and BWS case 1), and rheumatoid arthritis (RA; n = 982, DCE and probabilistic threshold technique [PTT]). In each study, results of the two methods were compared using a normalized preference measure for which confidence intervals (CIs) were estimated using nonparametric bootstrapping of 500 samples. Normalized preference measures comprised of mean relative attribute importance weights (NMD and diabetes studies), attribute uptake probability (MI study), or maximum acceptable risk (RA study).

In all four studies, attribute ranking showed similar patterns between DCE and other methods for the most important attributes. The same attribute had highest importance in three out of four studies. Significant differences were found in ranges of normalized preference measures of each study between DCE and the other methods: 4.1–43.4 versus 8.9–24.7 for DCE and BWS case 2 in NMD; 3.8–49.7 versus 11.9–16.8 for DCE and SW in diabetes; 2.0–85.5 versus 0.2–69.0 for DCE and BWS case 1 in MI; -3.5–49.2 versus 1.1–18.1 for DCE and PTT in RA.

Preferences differed significantly between DCE and other preference methods implying limited convergent validity. The substantially larger ranges in normalized outcome measures in DCE compared to other methods, are likely due to differences in mechanics and bias related to the methods. Since none of the methods is considered the golden standard for measuring stated preferences as true preferences are unknown, further studies are necessary to compare stated preference methods, determine internal validity and data quality, and potentially measure external validity.

Adequate pain relief at the scene of injury and during transport to hospital is a major challenge in all acute traumas, especially for those with hip fractures, whose injuries are difficult to immobilize and long-term outcomes may be adversely affected by administration of opiate analgesics. Fascia Iliaca Compartment Block (FICB) is a procedure routinely undertaken by clinicians in emergency departments for hip fracture patients, but use by paramedics at the scene of emergency calls, is not yet evaluated (1).

We undertook a randomized controlled feasibility trial using novel audited scratchcard randomization to allocate eligible patients to FICB or usual care. Paramedics are recruited and trained to assess patients for hip fracture and carry out FICB. We will follow up patients to assess accuracy of paramedic diagnosis, acceptability to patients and paramedics, compliance of paramedics and also measures of pain, side effects, time in hospital and quality of life in order to plan a full trial if appropriate. The primary outcome measure is health related quality of life, measured using Short Form (SF)-12 at 1 and 6 months. Interviews and focus groups will be used to understand acceptability of FICB to patients and paramedics. This study was funded by Health and Care Research Wales (1003).

We have developed:

• • paramedic pathway to assess patients for hip fracture and FICB

• • paramedic training package, delivered by Consultant Anaesthetist

• • randomization scratchcards.

To date we have recruited nineteen paramedics; ten are fully trained and recruiting patients, the remainder are being trained. Fifty-four patients have been randomized and thirty-five have consented to follow-up. Thirteen 1-month and five 6-month follow-up questionnaires have been received.

This study will enable us to recommend whether to undertake a definitive multi-centre randomized controlled trial of FICB by paramedics for hip fracture to determine if the procedure is effective for patients and worthwhile for the National Health Service.

This study aims to develop a framework for establishing priorities in the regional health service of Murcia, Spain, to facilitate the creation of a comprehensive multiple criteria decision analysis (MCDA) framework. This framework will aid in decision-making processes related to the assessment, reimbursement, and utilization of high-impact health technologies.

Based on the results of a review of existing frameworks for MCDA of health technologies, a set of criteria was proposed to be used in the context of evaluating high-impact health technologies. Key stakeholders within regional healthcare services, including clinical leaders and management personnel, participated in a focus group (n = 11) to discuss the proposed criteria and select the final fifteen. To elicit the weights of the criteria, two surveys were administered, one to a small sample of healthcare professionals (n = 35) and another to a larger representative sample of the general population (n = 494).

The responses obtained from health professionals in the weighting procedure exhibited greater consistency compared to those provided by the general public. The criteria more highly weighted were “Need for intervention” and “Intervention outcomes.” The weights finally assigned to each item in the multicriteria framework were derived as the equal-weighted sum of the mean weights from the two samples.

A multi-attribute function capable of generating a composite measure (multicriteria) to assess the value of high-impact health interventions has been developed. Furthermore, it is recommended to pilot this procedure in a specific decision context to evaluate the efficacy, feasibility, usefulness, and reliability of the proposed tool.

Alzheimer's disease (AD) is the most common type of dementia. Plasmapheresis is a procedure consisting of removing the plasma, or specific elements which are considered to be involved in pathological processes. Plasmapheresis could reduce the A beta peptides load in the brain. The objective is to study the safety and efficacy of plasmapheresis for AD.

Systematic review, with all studies published before April 2016 reviewed. Selected studies included patients with AD treated with plasmapheresis. GRADE was used to assess quality. Efficacy outcomes include: (i) Cognitive, functional and behavior status, through Mini Mental State Examination, and Alzheimer Disease Assessment Scale-Cognitive test; (ii) Plasma and cerebrospinal fluid A beta levels; (iii) Brain-imaging and functional neuroimaging studies. Safety outcomes included side effects related to the treatment.

Two papers reporting results from three studies were selected: (i) pilot study (n = 10), (ii) its extended study (12 months more of follow-up) (n = 7), and (iii) clinical trial (n = 39). The quality of evidence was very low. About efficacy, the studies didn't report quantitative results and were inconclusive. The pilot study and its extended study reported (1): a tendency towards stabilization in cognitive status; the plasma levels of A beta peptides didn't show a clear pattern; and the brain-imaging assessment suggested a progressive volume increase in the hippocampus. The clinical trial reported in the experimental group vs control (2): a better score for the cognitive status; an increase of plasma A beta peptides; and did not find significant differences between groups for cerebrospinal fluid A beta peptides. The brain-imaging assessment showed a progressive loss of hippocampus volume in both groups. Regarding safety, the studies didn't report quantitative data. We didn't find economic evaluation studies.

The included studies had very high risk of bias and very low quality. We found no evidence on efficacy and safety of plasmapheresis treating AD. Plasmapheresis isn't a priority line in research of AD treatment.

Unlike randomized controlled trials, lack of methodological rigor is a concern about real-world evidence (RWE) studies. The objective of this study was to characterize methodological practices of studies collecting pharmacoeconomic data in a real-world setting for the management of type 2 diabetes mellitus (T2DM).

A systematic literature review was performed using the PICO framework: population consisted of T2DM patients, interventions and comparators were any intervention for T2DM care or absence of intervention, and outcomes were resource utilization, productivity loss or utility. Only RWE studies were included, defined as studies that were not clinical trials and that collected de novo data (no retrospective analysis).

The literature search identified 1,158 potentially relevant studies, among which sixty were included in the literature review. Many studies showed a lack of transparency by not mentioning the source for outcome and exposure measurement, source for patient selection, number of study sites, recruitment duration, sample size calculation, sampling method, missing data, approbation by an ethics committee, obtaining patient's consent, conflicts of interest, and funding. A significant proportion of studies had poor quality scores and was at high risk of bias.

RWE from T2DM studies lacks transparency and credibility. There is a need for good procedural practices that can increase confidence in RWE studies. Standardized methodologies specifically adapted for RWE studies collecting pharmacoeconomic data for the management of T2DM could help future reimbursement decision making in this major public health problem.