Clinical decision support systems (CDSS) are being developed to support evidence-based antibiotic prescribing and reduce the risk of inappropriate or over-prescribing; however, adoption of CDSS into the health system is rarely sustained. We aimed to understand the implementation challenges at a macro (policymakers), meso (organizational) and micro-level (individual practices) to identify the drivers of CDSS non-adoption.

We have adopted a mixed-method study design which comprised of: (i) systematic review and meta-analysis to assess the impact of CDSS on appropriate antibiotic prescribing, (ii) Online survey of clinicians in Australia from hospitals and primary care to identify drivers of CDSS adoption and (iii) in-depth interviews with policymakers to evaluate policy-level challenges and opportunities to CDSS implementation.

CDSS implementation can improve compliance with antibiotic prescribing guidelines, with a relative decrease in mortality, volume of antibiotic use and length of hospital stay. However, CDSS provision alone is not enough to achieve these benefits. Important predictors of clinicians’ perception regarding CDSS adoption include the seniority of clinical end-users (years), use of CDSS, and the care setting. Clinicians in primary care and those with significant clinical experience are less likely to use CDSS due to a lack of trust in the system, fear of comprising professional autonomy, and patients’ expectations. Lack of important policy considerations for CDSS integration into a multi-stakeholder healthcare system has limited the organizational capacity to foster change and align processes to support the innovation.

These results using multiple lines of evidence highlight the importance of a holistic approach when undertaking health technology management. There needs to be system-wide guidance that integrates individual, organizational and system-level factors when implementing CDSS so that effective antibiotic stewardship can be facilitated.

Within the Home Radiology service of the Piedmont Region - R@dhome (1) - it was decided to employ a mobile radiological service to allow minor radiological procedures to be conducted in rural areas. Cortemilia (average age of population 51.6 years, population over 65 years 33.6 percent) is situated in Piedmont (Langhe region) and it is about 40 kilometers, with bad roads, from the nearest hospital. For this reason it's important to optimize the potential offered by telemedicine. The purpose of R@dhome is to provide simple radiological services (ambulatory) to vulnerable patients in outpatient settings. The aim of this work was to implement an assessment, based on Health Impact Analysis (HIA) (2,3) criteria, of the health intervention provided by the R@dhome service.

From January 2016 to December 2016 the following were assessed:

• • number of patients examined in the local radiological ambulatory service

• • inhabitants opinions (using questionnaires)

• • General Practitioner, Pharmacist, Family nurse opinions (using semi-structured interviews)

• • stakeholder opinions (Mayor, local politicians, using semi-structured interviews)

• • number of cars and ambulances used for the transport of patients to the nearest hospital

• • number of patients who avoided transportation to the nearest hospital

• • pollutants PM10 (particle size 10) related to cars and ambulance traffic.

Forty percent of people interviewed were more than 60 years old, 76 percent needed x-rays (in 2015), 96.8 percent considered it useful to have a closer x-ray service, only 42 percent had a driver's licence but preferred not to drive; GP's said that 50 percent of local patients had trouble reaching the hospital and that 30 percent of local patients need informal or formal care. From Januay to December 2016 we examined (mainly chest and bone x-rays) in 598 patients using as an alternative to private cars and ambulances the radiological mobile station, and the pollutant emissions were shown to be reduced by 85 percent.

This study has provided a comprehensive HIA report which shows that the R@dhome intervention improves patient's QOL, reduces social costs, reduces the number of patients in the Hospital Radiology Department, reduces rate of hospitalization and pollution.

Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of serious diseases in which patients are at risk of metabolic decompensation, resulting in cardiomyopathy, hypoglycemia and rhabdomyolysis and premature mortality. In addition, LC-FAOD are a burdensome disease that adversely effects quality of life (QoL) via symptoms of muscle pain, fatigue, and a difficult diet. Previous studies have reported improvements in QoL during treatment with triheptanoin as measured by short form (SF) instruments. This study sought to convert the QoL measure into a utility value for a sample of patients with LC-FAOD at baseline and 78 weeks during treatment with triheptanoin.

In an open-label Phase 2 study of triheptanoin (UX007-CL201, NCT01886378), caregivers of patients (n = 9/23 enrolled) or patients aged 18+ years (n = 6/6 enrolled) completed the SF-10 or the SF-12v2, respectively. Component summary scores at baseline and 78-week during treatment period were converted to EuroQol-Five Dimension (EQ-5D) utility (with zero representing death and 1.0 perfect health) using a published conversion algorithm (Lawrence and Fleishman 2004). Generalized linear mixed-effects models with individual-level random effects were used to estimate the utility values.

At baseline, patients’ utility was estimated to be 0.365 (standard error [SE] = 0.090) compared with 0.629 (SE = 0.072) 78-weeks during treatment, a significant improvement (p = 0.0073). In a sensitivity analysis using SF-12v2 data only (that is, only adult patients), utility estimates were 0.498 (SE = 0.084) at baseline versus 0.690 (SE = 0.068) during treatment (p = 0.0499). No patients had a major clinical event during the SF instrument recall period, indicating the benefit was driven by day-to-day improvement in QoL.

Treatment with triheptanoin resulted in a substantial improvement in daily QoL for patients with LC-FAOD. Limitations of this study include that the estimation of utilities is from a single-arm study with small sample sizes and that the assessment of utility was based on a conversion algorithm rather than direct measurement. Nevertheless, results indicate significant improvement in QoL for patients treated with triheptanoin.

Presenting an approach to synthesize quantitative and qualitative information from systematic reviews of multiple health interventions.

Within the context of an EUnetHTA multi-health technology assessment of twenty-three surgical techniques, we developed synthetic single tables, using color gradients and abbreviations, with information on which technologies had been compared, estimates of the size of differences for available comparisons, their clinical relevance, and certainty of the related evidence.

The proposed methodology provided, through a single depiction, information normally included in multiple figures/tables such as network plots, league tables, and summary of findings tables.

Transferring information on benefits, risks, and certainty of the available evidence on health interventions may be challenging, especially when assessing multiple treatments: more pieces of information need to be integrated in order to show an overall picture for each of the chosen outcomes, and usual reporting tools may be targeted to researchers more than to different kinds of decision makers. While more in-depth layers of information can always be added to satisfy needs of different audiences, the proposed tools could favor a quick interpretation of articulated scientific data by both decision makers and researchers.

Mobile health (mHealth) is increasingly being seen as a promising solution to the multiple health system challenges that Vietnam faces, including inadequate health service provision. Nevertheless, there is limited published information describing the sustainability of such mHealth solutions in the Vietnamese context. This study reviewed the available projects and interventions to evaluate factors challenging sustainability of mHealth initiatives in Vietnam.

A multimodal scoping study was designed to collect data from various sources: published literature, government reports, unpublished literature, conference presentations, online documents, and key informant interviews. Relevant mHealth initiatives were identified and selected through electronic searches and informal discussions with key stakeholders. Collected data was charted and classified by thematic analysis. Challenges to the sustainability of mHealth initiatives were discussed in the context of the strengths, weaknesses, opportunities, and threats (SWOT).

Twenty mHealth initiatives with relevant information and available data were collected, covering the period from 2010 to 2017. Fifteen (75 percent) were primarily funded by external donors, one (5 percent) was government supported, and four (20 percent) were self-funded projects. Five (25 percent) were on-going, and fifteen (75 percent) were completed at the time of data collection. Four (20 percent) out of the completed initiatives were continuing to use materials, infrastructure, and technology to engage end-users.

The high percentage of external funding, complicated governmental bureaucracy and lack of government commitment, electronic medical record standardization, and legislation relating to mHealth are amongst the largest challenges to mHealth sustainability in Vietnam. In addition, findings demonstrate it is crucial for project managers of mHealth initiatives to build strong relationships with the Vietnam government and advocate for their mHealth initiatives in order to promote sustainability.

As model-based economic evaluations (MBEEs) are widely used to make decisions in the context of policy, it is imperative that they represent clinical practice. Here, we assess the relevance of MBEEs on dabigatran for the prevention of stroke in patients with atrial fibrillation (AF).

We performed a systematic review on the basis of a developed questionnaire, tailored to oral anticoagulation in patients with AF. Included studies had a full body text in English, compared dabigatran with a vitamin K antagonist, were not dedicated to one or more subgroup(s), and yielded an incremental cost-effectiveness ratio. The relevance of all MBEEs was assessed on the basis of ten context-independent factors, which encompassed clinical outcomes and treatment duration. The MBEEs performed for the United States were assessed on the basis of seventeen context-dependent factors, which were related to the country's target population and clinical environment.

The search yielded twenty-nine MBEEs, of which six were performed for the United States. On average, 54 percent of the context-independent factors were included per study, and 37 percent of the seventeen context-dependent factors in the U.S. studies. The share of relevant factors per study did not increase over time.

MBEEs on dabigatran leave out several relevant factors, limiting their usefulness to decision makers. We strongly urge health economic researchers to improve the relevance of their MBEEs by including context-independent relevance factors, and modeling context-dependent factors befitting the decision context concerned.

To provide insights into the attributes of health-related quality of life (HRQoL) research within the context of economic evaluations for a potential national health technology assessment process in South Africa, and make evidence generation recommendations.

A systematic review was conducted in January 2019 using Medline, the Web of Science (WoS) Core Collection and the South African SciELO collection via the WoS Platform, and in the Cochrane Library. No time restrictions were applied. Duplicate records were removed before first- and second-pass screening by two reviewers working independently.

The review identified 123 publications representing 104 studies since the first-published article appeared in 1996. Only eight studies were randomized controlled trials, most were cross-sectional (n = 54). The EQ-5D, SF-36, and WHOQOL-BREF were the most used HRQoL instruments (n = 35, n = 23, and n = 10, respectively). Instruments were frequently administered in multiple languages, reflecting the cultural groups in which the study was conducted, with the English version of instruments used most often. Studies were predominantly conducted within the public health sector (n = 67), in the Western Cape province (n = 46), in adults (n = 92) and people with HIV (n = 24).

South African specific HRQoL studies have been conducted in a range of settings and populations using mostly generic HRQoL instruments in multiple languages. These studies may provide generalizable, real-world data due to their observational nature. However, more comparative and longitudinal studies should be conducted as this is preferred for economic evaluations and patient, disease, and treatment characteristics should be reported in full.

Advanced Therapy Medicinal Products (ATMPs) are innovative biologics (gene, cells and tissue-based products) with the potential to treat diseases with significant unmet clinical need. ATMPs pose distinct regulatory, health technology assessment (HTA) and patient access challenges, hence early identification and prioritization of ATMPs is now recognized as a key concern in England. The National Institute for Health Research Innovation Observatory (NIHRIO) uses a robust methodology to identify and monitor health technologies, including ATMPs that meet the remit of key HTA stakeholders in England. This analysis provides a global overview of the current ATMPs pipeline to administer useful insights for policymakers, funders and innovators.

NIHRIO's database tracks pharmaceuticals from phase I/II onwards, but this analysis focuses on late-stage development. The database (N > 12,000 records) was filtered to identify potential ATMPs using a predefined criteria based on the European Medicine's Agency's classification. Each record is categorized by stage: ‘Active’, (with an estimated three years to European licence); ‘Monitoring’ (in development with no licence date); and ‘Finished’, (output produced/discontinued and no longer tracked). Subsequently, records in ‘Active’ and ‘Monitoring’ were examined further.

Analysis identified 636 ATMPs: five percent ‘Active’, 40 percent ‘Monitoring’ and 55 percent ‘Finished’. ATMPs in the Active/Monitoring stages included: gene therapies (52%), somatic cells (43%) and tissue-engineered products (5%). Of these, 40 percent were oncological with the majority targeting hematological cancers (lymphomas). Prevalent non-oncology areas included musculoskeletal (10%) and ophthalmology (8%). Over one-third of trials were phase IIs, with almost half of all trials were based in the US.

The overarching findings here indicate increasing development of the ATMP pipeline towards indications with significant unmet clinical need. In oncology, the high prevalence of hematological ATMPs is largely due to recent chimeric antigen receptor T cells (CAR-T) innovation. In non-oncology areas, ATMP development is increasing due to advances in regenerative medicine. With a significant number of ATMPs projected to be licenced within three years, and many more in active late-stage trials, HTA bodies and health systems are challenged to prepare for the entry of these innovative therapies.

The Canadian Agency for Drugs and Technologies in Health (CADTH) pan-Canadian Oncology Drug Review (pCODR) plays an important role in public reimbursement decision-making for oncology drugs in Canada. This research studies the relation of positive pCODR decisions to new cancer treatment and their subsequent inclusion in Canada's public drug plans.

We studied all oncology drugs that received an approval from Health Canada and were reviewed by the pCODR from inception till 26th Sep, 2017. The data was obtained from CADTH and Health Canada. Data such as indication, submission type and date, recommendation date, final recommendation, and subsequent provincial funding status was extracted and analyzed. Impact was evaluated by analyzing the percentage of drug submissions with assessment outcome (positive recommendation rate and conditional recommendation rate) and time taken for the final decision (recommendation gap). The percentage of drugs included in public formulary after positive recommendation by pCODR (coverage rate) and the gap in days from positive recommendation to subsequent coverage in provinces (coverage gap) was also assessed.

Among 119 drugs reviewed by pCODR, the positive recommendation rate was eight percent. Nine applications comprising seven drugs for six indications received positive recommendations, and genitourinary treatments received maximum positive recommendations. The conditional recommendation rate was 52 percent; 62 applications of 45 drugs for 46 indications received conditional recommendation. Lymphoma and myeloma treatments received maximum conditional recommendations. The average recommendation gap for positive and conditional recommendations was 180 and 172 days, respectively. The coverage rate for drugs with positive recommendation was 100 percent for all provinces except 89 percent for Newfoundland and Labrador, and 67 percent for Prince Edward Island. Among the provinces, British Columbia had a maximum of 433 days and Saskatchewan has the minimum of 165 days coverage gap.

Despite Health Canada's approval, only a fraction of oncology drugs receive positive pCODR recommendation; furthermore, provincial drug plans take time to include these in the reimbursement formularies. While health technology assessment is crucial for appropriate allocation of limited resources, efforts should also be made to reduce access barriers, particularly to positively recommended oncology drugs inclusion in provincial formularies.

The frameworks used by Health Technology Assessment (HTA) agencies for value assessment of medicines aim to optimize healthcare resource allocation. However, they may not be effective at capturing the value of antimicrobial drugs.

To analyze stakeholder perceptions regarding how antimicrobials are assessed for value for reimbursement purposes and how the Australian HTA framework accommodates the unique attributes of antimicrobials in cost-effectiveness evaluation.

Eighteen individuals representing the pharmaceutical industry or policy-makers were interviewed. Interviews were transcribed verbatim, coded, and thematically analyzed.

Key emergent themes were that reimbursement decision-making should consider the antibiotic spectrum when assessing value, risk of shortages, the impact of procurement processes on low-priced comparators, and the need for methodological transparency when antimicrobials are incorporated into the economic evaluation of other treatments.

Participants agreed that the current HTA framework for antimicrobial value assessment is inadequate to properly inform funding decisions, as the contemporary definition of cost-effectiveness fails to explicitly incorporate the risk of future resistance. Policy-makers were uncertain about how to incorporate future resistance into economic evaluations without a systematic method to capture costs avoided due to good stewardship. Lacking financial reward for the benefits of narrower-spectrum antimicrobials, companies will likely focus on developing broad-spectrum agents with wider potential use. The perceived risks of shortages have influenced the funding of generic antimicrobials in Australia, with policy-makers suggesting a willingness to pay more for assured supply. Although antibiotics often underpin the effectiveness of other medicines, it is unclear how this is incorporated into economic models.

Next-generation sequencing (NGS) can be run in-house or outsourced to an independent laboratory. It has enabled wider use of deoxyribonucleic acid/ribonucleic acid (DNA + RNA) sequencing in clinical practice. Within oncology, NGS has paved the way for more effective treatment, including personalized medicine. There are, however, large variations in access and reimbursement across Europe. The aim is to understand the European NGS landscape and barriers to access.

Structured telephone interviews covered topics on NGS perception, guidelines, use-cases, benefits, costs, and future expectations. Twelve experts per country (France, Germany, Italy, Spain): two payers, five oncologists, and five pathologists were interviewed between June and August 2021. Responses were translated into English for qualitative analysis.

NGS was considered most useful when there were approved, targeted treatments. Although often noted that there was a lack of published evidence to support a beneficial link, respondents perceived that NGS has the potential to improve patient quality of life (QoL) and reduce resource use through avoiding suboptimal treatment. All of the payer respondents expected the role of NGS to increase, though it may be held back by lack of reimbursement. Respondents favored in-house NGS over outsourcing in terms of clinical benefit: “Advantages of in-house NGS are turnaround time, results and lean processes” … “you build the expertise in-house. If you have urgent samples, it’s easy to prioritize them”. Reasons for not having in-house NGS included “costs, lack of personnel. Basically, organizational and financial issues.” In-house NGS was perceived to be associated with high setup-costs (acquisition, setup, training), but lower running costs (per-test costs). There was a view that in-house solutions are mainly suitable in larger centers undertaking many tests.

NGS can save costs and provide QoL benefit through enabling optimized, personalized therapy, but published evidence establishing the outcomes link is lacking. From the hospital perspective, investing in NGS requires understanding the cost of NGS over its entire lifecycle, likely entailing a health-technology assessment including health-economic analysis.

Along with the exponential growth of technology, the use of mobile devices in health, or mHealth, has been quickly becoming a viable practice to strengthen health systems, especially in low-resource settings. Nevertheless, the majority of mHealth interventions are pilot efforts which mostly lack robust design and evidence about the use of mHealth in public health. This study assessed the use of a bi-directional Short Message Service (SMS) in disease surveillance in Vietnam and aimed to bring evidence in improving engagement of health staff as well as the quality of reporting.

Eighty health staff from fourty communes of Hoa Binh and Hung Yen provinces were trained and participated in two 6-month pilots: one with one-way, and one with a bi-directional SMS system for assisting in error screening, and reminder and feedback provision to report two diseases: influenza and diarrhea using cell phones. After each examination and checking-in onto the paper logbook, participants reported the case by texting an SMS to a designated number and made notes of successfully reported cases. A central data repository server was set up to collect SMS reports, and aggregate reported patient data. Engagement of health staff and quality of the reporting work were assessed by the evaluation of the qualitative questionnaires, and the comparison of the texted SMS reports to the patient logbooks.

With the use of a two-way versus one-way SMS system, participants were 4.6 times more likely (95 percent Confidence Interval, CI 3.93-5.44, p< .001) to send correctly formatted text reports, and 3.4 times more likely (95 percent CI 2.72-4.33, p< .001) to have precise information in their texted messages. Results also revealed that while their position, age, or gender of participants did not statistically influence the results, ethnicity and management roles did.

The study showed that the use of a bi-directional SMS-based reporting system both significantly improved participants engagement in the reporting protocol, and greatly enhanced their reporting quality. The study demonstrated that robust evidence of a practical utilization of SMS in a disease reporting system to replace the traditional paper-based one has great potential for a scale-up and national-wide implementation.

For the last decades, health technology assessment has been strongly promoted in order to provide evidence-based rather than eminence-based healthcare. However, when it comes to implementing interventions that are based on processes and behavior rather than products, importing evidence-based interventions is likely to fail because it ignores the strong influence of contextual factors. In a recently started research project, an alternative approach is tested.

The project aims at improving identification and support of children who have parents with a mental illness in an Austrian region (Tyrol). A theory- and stakeholder-driven approach has been designed in order to co-develop, implement and evaluate practice approaches for improving the situation for children. The former addresses the questions whether, how and why suggested practices may work and the later brings together evidence and practice to develop interventions that are feasible and take the regional context and service settings into account.

Based on evidence from various sources (literature, international and local stakeholder interviews), theories that describe the key mechanisms of action to influence outcomes for children have been developed. A regional and interdisciplinary group of practitioners and people with lived experience has been established to facilitate the development of the theory of change and practice approaches for the region and local service settings. The final practice model is then monitored in the respective organizations with implementation support from the research team.

Theory-driven and co-designed-based approaches are a feasible alternative to ‘off-the-shelf’ evidence-based practices for supporting decision makers in implementing complex interventions. However, they require a broad variety of skills within the research team as well as willingness to accept uncertainties of the final outcomes produced, which can also be of risk to funders. The ongoing project will demonstrate whether the developed practices will be implemented successfully and result in benefits for the affected children.