Evaluating the impact of patient involvement in health technology assessments (HTA) may help improve practices and avoid ineffective activities. Evaluation, however, continues to be infrequent, inconsistent, and often only relates to process quantity or quality. The Patient and Citizen Involvement in HTA Interest Group (PCIG) within Health Technology Assessment International set out to contextualize this impact to support evaluation.

Given the lack of established methodology to measure impact, the team performed a qualitative analysis of first-hand accounts about perceived changes in HTA due to involvement of patient stakeholders. A questionnaire was developed, piloted, and rolled out to collect personal perspectives from stakeholders with relevant experience. The stories were analyzed in the aggregate to identify themes in the data.

From January 2019 to September 2021, twenty-four responses were collected through PCIG’s network. Responses (including one joint industry-HTA body submission) came from patient representatives (12), HTA bodies (11), and industry representatives (2) from North America (5), South America (3), Europe (13), and Asia Pacific (3). Based on themes commonly reported, a three-domain framework for evaluating impact is proposed: impact on basis of HTA result or recommendation, impact on HTA body, and impact on patient participants. The framework includes components under each domain to support reporting.

Using the Three-Domain Impact Framework may be useful in identifying, evaluating, and communicating the value of patient involvement in HTA. Enhancing and increasing reporting practices may improve transparency and facilitate process improvements for meaningful integration of patient stakeholders into HTA appraisals across jurisdictions.

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.

Recently, there have been calls for the development of new health technology assessment (HTA) methodologies to address the growing emergence of novel digital health technologies (DHTs). In particular, the lack of robust evidence base and technology-specific considerations of DHTs, such as software updates, present challenges for evaluation with conventional HTA methods. In Singapore, the Agency for Care Effectiveness (ACE) has established a horizon scanning (HS) system to provide the healthcare system with advance notice on emerging medical technologies (MedTechs) that may enter the Singapore market. This study aims to investigate the anticipated emergence of DHTs identified by ACE’s HS system and the potential implications on subsequent HTA methodology.

Based on ACE’s HS methodology, which is in line with international best practices, new and emerging MedTechs that address the top five local disease burden (i.e., cardiovascular, cancer, mental, neurological and musculoskeletal disorders) were identified from various sources and monitored for its development. These MedTechs were further filtered to shortlist potential technologies for HS assessment based on its innovative nature and appropriate time horizon to local regulatory approval. For this exercise, the filtered MedTechs were classified into categories such as DHTs, comprising technologies involving software or artificial intelligence (AI), and non-DHTs.

Between 2021 and 2022, ACE has completed two topic filtration exercises. Based on 807 and 1,231 monitored MedTechs, 35 and 42 technologies remained after filtration, respectively. Among them, six out of 35 (17%) and 15 out of 42 (36%) filtered MedTechs were classified as DHTs, accounting for approximately two-fold increase in the number of DHTs shortlisted year-on-year. These DHTs include standalone AI software, software in a medical device, and digital therapeutics.

There is a substantial increase in DHTs identified that are anticipated to enter the local healthcare system. Given their unique characteristics, this may call for the modification of current HTA method to enable meaningful evaluation of DHTs.

The aim of this study was to deliver insights from multiple stakeholders into actual and future collaboration for health technology assessment (HTA) in general and in oncology in particular.

Eighteen semi-structured interviews were conducted with experts from European HTA bodies (HTAbs), former board members of the European Network for Health Technology Assessment (EUnetHTA), and representatives from the pharmaceutical industry, a regulatory agency, academia, and patient organizations. The stakeholders were asked about their support of the EUnetHTA’s intent, about the general strengths and challenges of the EUnetHTA and its Joint Action 3 (JA 3), the strengths and challenges of the clinically oriented HTA collaboration in oncology during JA 3 across the technology life cycle, about future challenges to HTA in oncology with consequences for collaboration, and about collaboration in the economic domains of HTA. The transcribed interviews were analyzed qualitatively.

The participants perceived the intention and work quality of the EUnetHTA as positive. The experts described methodological, procedural, and capacity challenges in early dialogues (EDs) and rapid relative effectiveness assessments (REAs) meant to analyze clinical effectiveness in oncology. The majority attached increasing importance to collaboration in the future to cope with the uncertainty of HTA. Several stakeholders also proposed the incorporation of joint postlaunch evidence generation (PLEG) activities. Some gave sporadic suggestions for voluntary nonclinical collaboration as well.

Stakeholders’ continued readiness to discuss the remaining challenges to and sufficient resources for implementing HTA regulation, as well as further cooperative expansion along the technology life cycle, are necessary for improved HTA collaboration in Europe.

Aiming for hepatitis C elimination by 2030, Taiwan has set up a mid-term goal of “over 50 percent of patients treated by 2025.” Among various aspects of evidence that are needed, the target number to be treated is difficult to estimate with certainty due to great geographical heterogeneity of hepatitis C prevalence, and the absence of a nation-wide large scale prevalence survey.

A broad estimate of the number of patients to be treated with high uncertainty was calculated, and reimbursement criteria were set for year 2017 given limited data and treatment budget. In the meanwhile, various sources and approaches to estimate the target number to be treated, and to identify the high prevalence areas, were collected and synthesized for future planning through a systematic review of published data and consulting experts for unpublished data. An expert panel was consulted for the level of confidence and completeness of the evidence. A plan for using real-world data to reduce the uncertainty after initial actions of national program was also in place.

Eight thousand patients who fulfilled the reimbursement criteria were treated in 2017 as planned. Strategic steps were identified based on the collected data, and the treatment target, namely 200,000 patients to be treated during 2018 to 2025, was then set for appropriate action plans. National registry infrastructure is planned for supporting future policy modification.

Hepatitis C elimination is an important public health task and it requires immediate actions. The expected expenses are high, yet the number of patients is difficult to estimate with precision. How to deal with this uncertainty (financially and in care program design) will be the most challenging part. An adaptive approach (“evidence”-”action”-”more evidence”-”modified action”) could be the pragmatic way to move forward without sacrificing the quality of decision-making.

Population-based colorectal cancer (CRC) screening programs that use a fecal immunochemical test (FIT) are often faced with a noncompliance issue and its subsequent waiting time (WT) for those FIT positives complying with confirmatory diagnosis. We aimed to identify factors associated with both of the correlated problems in the same model.

A total of 294,469 subjects, either with positive FIT test results or having a family history, collected from 2004 to 2013 were enrolled for analysis. We applied a hurdle Poisson regression model to accommodate the hurdle of compliance and also its related WT for undergoing colonoscopy while assessing factors responsible for the mixture of the two outcomes.

The effect on compliance and WT varied with contextual factors, such as geographic areas, type of screening units, and level of urbanization. The hurdle score, representing the risk score in association with noncompliance, and the WT score, reflecting the rate of taking colonoscopy, were used to classify subjects into each of three groups representing the degree of compliance and the level of health awareness.

Our model was not only successfully applied to evaluating factors associated with the compliance and the WT distribution, but also developed into a useful assessment model for stratifying the risk and predicting whether and when screenees comply with the procedure of receiving confirmatory diagnosis given contextual factors and individual characteristics.

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.

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.

Intention to treat (ITT) is a gold standard strategy to analyze the results of randomized controlled trials (RCTs). ITT analysis has been considered a methodological indicator of the quality of clinical trials. The extent to which the use of ITT is related to the treatment effects observed in RCTs has not been rigorously explored. Therefore, the main objective of this study was to determine the association between biases related to attrition and missing data and the use of intention to treat principle, and changes in effect size estimates in RCTs.

This was a meta-epidemiological study. A random sample of RCTs included in meta-analyses was identified. Data extraction including assessments of the use of intention to treat principle, missing data and drop-outs was conducted independently by two reviewers. To determine the association between biases related to attrition, missing data, and the use of intention to treat and effect sizes, a two-level analysis was conducted using a meta-meta-analytic approach.

Three-hundred and ninety-three trials included in 43 meta-analyses, analyzing 44,622 patients contributed to this study. From these, 134 trials (34.1%) used ITT and 218 (55.5%) did not use ITT. Trials which did not use the ITT principle, or which were assessed as having an inappropriate control of incomplete outcome data (based on the Cochrane risk of bias tool) tended to underestimate the treatment effect when compared with trials with adequate use of ITT (ES= -0.13; 95%CI -0.26, -0.01) or trials which were assessed as having an appropriate control of incomplete outcome (ES= -0.18; 95%CI -0.29, -0.08).

Our results suggest that when evaluating risk of bias of primary RCTs, systematic reviewers should pay attention to these biases since they could underestimate treatment effects. Systematic reviewers should perform sensitivity analysis including trials with low risk of bias in these domains.

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.

Cystic Fibrosis (CF) is a genetic disorder caused by mutations in CFTR gene. In Italy, reported prevalence is approximately .70 per 10,000 inhabitants (1). The practice and recommendations for Cystic Fibrosis carrier screening are very heterogeneous in Europe. A proposal of a carrier genetic test in the general population raises many questions. Health Technology Assessment (HTA) could offer a sound methodological basis for this evaluation. The aim of this work was to summarize the available evidence, using the HTA approach, on the genetic tests for Cystic Fibrosis carrier screening.

A systematic literature search was used to find the best available international and national evidence on genetics test for CF carrier screening. In this report, we specifically addressed the health problem of disease, description and technical characteristics of tests – its analytic and clinical validity, and clinical utility. Economic evaluation of different scenarios was synthesized from the literature. Ethical, organizational, and social aspects of CF and genetic screening were also considered.

Several screening strategies have been evaluated in the literature and screening options can be characterized by different timing, model and place of screening (2). The reported cost of a screening test ranged from EUR25 to EUR212 (3). Estimated life time cost of care for CF patients ranged from EUR291,048 to EUR1,105,452. Ethical analysis emphasized that the use of these tests is an advantage in terms of the acquisition of knowledge and of responsible management of choices, but at the same time raises many ethical questions. Social considerations reported among patients and their families an overall positive attitude toward population CF carrier screening.

The advances in the molecular genetics technology have made CF carrier testing reliable and affordable. The multidisciplinary approach of this HTA provided an evidence-based evaluation of genetic tests and offers a firm scientific background for the decision-makers to consider the implementation of a screening for Cystic Fibrosis carriers into the Italian health care system.

Patient-reported outcomes (PRO) data are important in understanding patients’ experience of disease and treatment; however, PRO data are not universally collected or consistently included as part of a Health Technology Assessment (HTA) submission. Additionally, the HTA bodies’ response to PRO data vary, making the impact unclear. To understand the impact of PRO data on reimbursement decisions for Acute Myeloid Leukemia (AML) indications, an in-depth analysis of HTA bodies’ appraisals of AML and analogous indications was conducted.

This analysis was conducted using IQVIA's HTA Accelerator, which contains HTA appraisals from ≥100 HTA agencies in thirty-nine countries. Included in the analysis were single-technology assessments (original submissions, resubmissions, extensions of original indications, and renewals); relevant regulatory approvals and pivotal trials were also analyzed.

Of the 185 AML appraisals from sixteen HTA bodies, 66 (36%) included PRO data. Within these, thirteen different PRO instruments were identified, none of which have been validated in patients with AML. For seven of twenty in-scope products, PRO evidence positively impacted ≥1 of the HTA decisions. Although the same HTA bodies (i.e., Scottish Medicines Consortium, pan-Canadian Oncology Drug Review, and the National Institute of Health and Care Excellence) generally accepted the PRO evidence, others were critical of the evidence (i.e., Haute Autorité de Santé and the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen). The most common concerns raised by the HTA bodies regarding the PRO evidence included trial design and low patient response rate.

Of the products that included PRO evidence in their HTA submissions, 35% received positive feedback from ≥1 HTA body on their submitted PRO evidence. Attention to PRO data collection is key to demonstrate the value of AML products to HTA bodies. Without these data, a clear gap in the understanding of patients’ experience is evident.

There is increased recognition of the need to include equity considerations in HTA. Despite this, a recent World Health Organization report has found that this is seldom the case. We developed a preliminary version of an equity checklist in the hopes that tangible guidance will increase such analyses in the future and contribute to smart capability building.

The checklist is based on the Equity Framework for HTA developed by Culyer & Bombard (2012). The elements presented in the framework were revised to follow the stepwise HTA process. A comprehensive literature search was used to update and complete the elements. The checklist was then piloted in an HTA in 2018 and subsequently further refined through a workshop during a national HTA conference in Canada.

These steps resulted in a 27-item checklist leading to consider different aspects of the three major phases in the HTA process. The scoping phase brings questions relative to defining and contextualizing equity, such as highlighting potential minority groups and including vulnerability factors in the logic model. The development phase leads methodological approaches facilitating the analysis of inequities as well as considering contextual realities leading to inequities. The last phase, drafting of recommendations, aims to be aware of the evidence synthesis approaches as well as the various aspects to ensure recommendations consider existing inequities and avoid contributing to their development.

Given the essence of HTA to protect health by ensuring optimal technologies and interventions are adopted to the benefit of all system users, the consideration of inequities should constitute an integral part of its process. The use of a pragmatic and simple checklist to aid the planning of an HTA could contribute to greater consideration of inequities in the future. A movement in this direction could also lead to greater methodological developments for health equity analysis in HTA.

Patients with hematological malignancies are likely to develop hypogammaglobulinemia. Immunoglobulin (Ig) is commonly given to prevent infections, but its overall costs and cost-effectiveness are unknown.

A systematic review was conducted following the PRISMA guidelines to assess the evidence on the costs and cost-effectiveness of Ig, administered intravenously (IVIg) or subcutaneously (SCIg), in adults with hematological malignancies.

Six studies met the inclusion criteria, and only two economic evaluations were identified; one cost-utility analysis (CUA) of IVIg versus no Ig, and another comparing IVIg with SCIg. The quality of the evidence was low. Compared to no treatment, Ig reduced hospitalization rates. One study reported no significant change in hospitalizations following a program to reduce IVIg use, and an observational study comparing IVIg with SCIg suggested that there were more hospitalizations with SCIg but lower overall costs per patient. The CUA comparing IVIg versus no Ig suggested that IVIg treatment was not cost-effective, and the other CUA comparing IVIg to SCIg found that home-based SCIg was more cost-effective than IVIg, but both studies had serious limitations.

Our review highlighted key gaps in the literature: the cost-effectiveness of Ig in patients with hematological malignancies is very uncertain. Despite increasing Ig use worldwide, there are limited data regarding the total direct and indirect costs of treatment, and the optimal use of Ig and downstream implications for healthcare resource use and costs remain unclear. Given the paucity of evidence on the costs and cost-effectiveness of Ig treatment in this population, further health economic research is warranted.

Appropriate resource utilization is crucial for cancer screening programs. Overscreening is defined as screening provided beyond the upper age limit of the target age or at a shorter interval than recommended in national programs. In Japan, there are no upper age limits set for cancer screening programs, and the recommended screening interval for cervical and breast cancer screening is 2 years. To examine the efficient use of resources for cervical and breast cancer screening, we investigated how often overscreening occurred in both programs.

The target age for this study was defined as 20-69 years for cervical cancer screening and 40-69 years for breast cancer screening. We used the national report for cancer screening in 2017 in Japan and estimated the number of participants over 70 years old or those who participated in screening annually. The percentage of overscreening was compared between cervical cancer and breast cancer screening by chi-square test.

The number of participants was 4,294,127 for cervical cancer screening and 3,087,781 for breast cancer screening in 2017. The percentage of overscreening in total participants was 38.0 percent for cervical cancer screening and 35.7 percent for breast cancer screening (p<0.01). The percentage of screening at overage was higher in breast cancer screening than in cervical cancer screening (21.1% vs. 13.9%, p<0.01), whereas more frequent screening was seen more often in cervical cancer screening than in breast cancer screening (29.7% vs. 19.6%, p<0.01). If the resources used in overscreening could be used for the target population, it was estimated that the participation rate could increase by 4.1% for cervical cancer screening and 4.3% for breast cancer screening.

In Japan, screening for overage participants and short intervals may have contributed to unnecessary screening for cervical cancer and breast cancer. These resources used for overscreening could be allocated to screening for the target population.

Under the national guidance of Internet Plus Healthcare, Internet hospital was officially recognized in 2018 by the Chinese government, however, how to innovate the business models of Internet hospitals remains controversial. This study sought to explore key stakeholders’ perspectives on key dilemmas about innovative business models of Internet hospitals in China.

A focus group study of key stakeholders was performed. Twelve key stakeholders (six senior officials from related ministries, two industry practitioners of Internet medicine, one hospital leader, two healthcare researchers (financing and policy), and one venture capital manager) participated in the focus group, in 2019. Thematic content analysis was applied for data analysis.

Themes highlighted six key dilemmas when developing a business model of Internet hospitals, including (i) value proposition (medical treatment versus entire health management); (ii) leading party (hospitals versus third parties such as Internet companies); (iii) level of healthcare (tertiary versus primary); (iv) scope of service (provide full range versus part of traditional hospital service); (v) primary source of revenue (medical services versus drug sales); and (vi) legal liability (web-based unit versus physical hospital).

The healthcare industry is currently in search of innovative business models of Internet hospitals in response to the unprecedented form of healthcare in China. However, the core aspects of the model design still remain debatable. At this revolutionary stage, policies are important to allow the implementation of different model designs that support the successful transformation of the entire health care system in China.