Health Canada is committed to the modernization of the use of real-world data (RWD) and evidence (RWE) to support regulatory decisions. As such, telephone interviews with stakeholders, including government decision makers, health technology assessment (HTA) producers, industry, and patients, to understand their experiences with and perspectives on how to enhance RWE use for medical devices were performed.

Thirty-four semi-structured telephone interviews with forty key informants were conducted. Transcripts were reviewed independently by one individual to identify, define, and categorize key concepts and were verified by a second reviewer.

There are expectations for Health Canada to provide a framework and guidance on RWE use, identify relevant outcomes for data collection and criteria for data quality, conduct post-market surveillance more systematically, and partner with HTA organizations to develop methods for RWE generation. Stakeholders interviewed support the RWE use for regulatory decisions and HTA recommendations. Moreover, robust scientific methods for RWE generation will be critical to ensure that relevant questions are asked and rigorous statistical analyses are done to answer them. Patients are likely to consent to share their anonymized or de-identified medical information for nonprofit purposes.

Key concepts from the interviews centered on the current and future RWE use for medical devices, considerations for the organizational, medical, scientific, and legal aspects and privacy issues of RWD collection or RWE generation, and options to implement the use of RWD and RWE. Our study findings will help inform the development of an RWE framework for regulatory decisions and HTA recommendations.

Our aim was to assess the value of nintedanib for non-idiopathic progressive fibrosing interstitial lung disease (non-IPF PF-ILD) and systemic sclerosis-associated ILD (SSc-ILD) in the Spanish context, using a multi-criteria decision analysis (MCDA).

Following an adaptation of the Evidence and Value: Impact on DEcision Making (EVIDEM) MCDA methodology, the estimated value of nintedanib was obtained by means of an additive linear model that combined individual weights (100-points distribution) of criteria with the individual scoring of nintedanib in each criterion for every indication, assigned by a multidisciplinary committee of twelve clinicians, patients, pharmacists, and decision-makers. To assess the reproducibility, an alternative weighting method was applied, as well as a re-test of weights and scores at a different moment of time.

The experts committee recognized nintedanib as an intervention with a positive value contribution in comparison to placebo for the treatment of non-IPF PF-ILD (0.50 ± 0.16, on a scale from −1 to 1) and SSc-ILD (0.40 ± 0.12), diseases which were considered as very severe and with high unmet needs. The drug was perceived as a treatment that provides an added therapeutic benefit for patients (0.06–0.07), given its proven clinical efficacy (0.05–0.06), slight improvements in patient-reported outcomes (0.01–0.02), and similar safety profile than placebo (−0.04–0.00), which will likely be positioned as a recommended therapy in the next clinical practice guidelines updates.

Under this increasingly used methodology, nintedanib has shown to provide a positive value estimate for non-IPF PF-ILD and SSc-ILD when compared to placebo in Spain.

To investigate the behavior of restricted mean survival time (RMST) and designs of a two-state Markov microsimulation model through a 2 × 4 × 2 full factorial experiment.

By projecting patient-wise 15-year-post-trial survival, we estimated life-year-gained between an intervention and a control group using data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies Study (COMPASS). Projections considered either in-trial events or post-trial medications. They were compared based on three factors: (i) choice of probability of death, (ii) lengths of cycle, and (iii) usage of half-a-cycle age correction. Three-way analysis of variance and post-hoc Tukey's Honest Significant Difference test compared means among factors.

When both in-trial events and post-trial study medications were considered, monthly, quarterly, or semiannually were not different from one other in projected life-year-gained. However, the annual one was different from the others: mean and 95 percent confidence interval 252.2 (190.5–313.9) days monthly, 251.8 (192.0–311.6) quarterly, 249.1 (189.7–308.5) semiannually, and 240.8 (178.5–303.1) annually. The other two factors also impacted life-year-gained: background probability (269.1 [260.3–277.9] days projected with REACH-based-probabilities, 227.7 [212.6–242.8] with a USA life table); half-a-cycle age correction (245.5 [199.0–292] with correction and 251.4 [209.1–293.7] without correction). When not considering post-trial medications, only the choice of probability of death appeared to impact life-year-gained.

For a large trial or cohort, to optimally project life-year-gained, one should consider using (i) annual projections, (ii) life table probabilities, (iii) in-trial events, and (iv) post-trial medication use.

To assess the clinical effectiveness of fluticasone furoate nasal spray (FFNS) versus placebo on nasal symptoms and safety in children with perennial allergic rhinitis (AR).

A comprehensive review was conducted with data obtained from Medline and Embase databases up to April 2023. The population of interest was patients aged 2–12 years with perennial AR. The selection was limited to randomized controlled trials (RCTs), comparing FFNS with placebo. Outcomes of interest included the reflective total nasal symptoms scores (rTNSS) and safety. To assess the minimal clinically important difference for rTNSS, the Cohen’s guideline was used. If the pooled standardized mean difference (SMD) and the lower limit of the 95 percent confidence interval (CI) exceeded the threshold of −0.20, effects were considered clinically significant.

Three RCTs (959 pediatric patients) were selected. One study evaluated the short-term use of FFNS, another evaluated the long-term use of FFNS, and another evaluated both the short-term and long-term use of FFNS. FFNS produced a statistically significant reduction over placebo in rTNSS (SMD −0.18; 95 percent CI −0.35 to −0.01, p = 0.03) in long-term treatment studies, but not in short-term treatment studies. However, since the mean reduction did not reach the minimum clinically important difference (SMD −0.20), these results were considered clinically not relevant. Safety outcomes with FFNS were similar to placebo.

The currently available evidence suggests that FFNS, 110 μg once daily, compared to placebo, does not produce a meaningful clinical effect on nasal symptom in children with perennial AR.

We examined relationships between measures of total knee arthroplasty (TKA) “appropriateness” constructs and surgeon TKA recommendations in people with knee osteoarthritis (OA). Although TKA is highly effective, fifteen to thirty percent of recipients report dissatisfaction and/or little or no symptom improvement. More appropriate selection of surgical candidates may improve both patient outcomes and healthcare resource use, but no validated appropriateness criteria exist currently in Canada.

Patients 30 years of age or older with knee OA referred for surgical consultation at two large joint arthroplasty centres in Alberta, Canada were invited to participate. Participants completed a standardized pre-consult questionnaire, which included the following sociodemographics and validated measures of appropriateness constructs for TKA: knee symptoms; non-surgical management; patient readiness for and expectations of TKA; and net patient benefit. Post-consultation, surgeons were asked to confirm knee OA and their recommendation. We used multivariable logistic regression to examine the relationship between measures of appropriateness constructs and receipt of surgeon TKA recommendation.

Of 3,009 patients approached, 2,360 completed the questionnaire and 2,064 (sixty-nine percent) were eligible at surgical consultation (mean age 65.7 years, standard deviation 9.1; fifty-nine percent were women); 1,495 (seventy-two percent) were recommended for TKA. The likelihood of receiving a TKA recommendation was independently associated with: knee symptoms (odds ratio [OR] per unit increase in pain intensity, 1.19 (95% confidence interval [CI]: 1.11–1.27)); prior non-surgical OA management (OR for prior knee injection, 1.53 (95% CI: 1.21–1.94)); readiness for surgery (OR if definitely/probably willing to undergo TKA, 3.03 (95% CI: 1.99–4.59)); and TKA expectations (OR outcome “very important”: ability to perform daily activities, 1.40 (95% CI: 1.04–1.88); straighten the knee/leg 1.42 (95% CI: 1.13–1.80); participate in exercise/sports 0.75 (95% CI: 0.58–0.98)).

In our cohort of patients with confirmed knee OA who consulted a surgeon for TKA, appropriateness constructs were significantly associated with receipt of a TKA recommendation. Research is ongoing to evaluate the predictive validity of these measures for patient-reported outcomes associated with TKA.

Australians are adjusting to mobile health (mHealth) applications (apps) being used in clinical care. The nature of apps presents unique challenges (e.g. rapid lifecycle) to mHealth regulation. The risks they pose are mainly through the information they provide and how it is used in clinical decision-making. This study explores the international regulation of mHealth apps. It assesses whether the approach used in Australia to regulate apps is consistent with international standards and suitable to address the unique challenges presented by the technology.

A policy analysis was conducted of all nine member jurisdictions of the International Medical Device Regulator's Forum (IMDRF), to determine if their regulatory agencies addressed the IMDRF recommendations relevant to the clinical evaluation of mHealth apps. Case-studies (submission to regulatory agencies) were also selected on varying types of regulated apps (standalone, active implantable, etc.) and assessed relative to the principles in the IMDRF's software as a medical device (SaMD): Clinical evaluation (2017) guidance document.

All included jurisdictions evaluated the effectiveness of mHealth apps, assessing the majority of the key sub-categories recommended by SaMD: Clinical evaluation. The submissions and jurisdictional regulatory bodies did not address the IMDRF safety principles in terms of the apps’ information security (cybersecurity). Furthermore, by failing to use the method recommended by the IMDRF (risk-classification), none of the submissions or jurisdictions recognized the potential dangers of misinformation on patient safety.

None of the approaches used by global regulatory bodies adequately address the unique challenges posed by apps. Australia's approach is consistent with app regulatory procedures used internationally. We recommend that mHealth apps are evaluated for cybersecurity and are also classified using the IMDRF risk-categories so as to fully protect the public.

Hemodialysis (HD) and peritoneal dialysis (PD) are commonly used to treat patients with end-stage renal disease (ESRD). However, their costs have grown considerably in recent years as the rates of non-communicable diseases including diabetes and hypertension have grown. This will adversely impact on national health budgets especially in low- and middle-income countries (LMICs). Currently, there is limited knowledge about the costs of ESRD and the different components within the public healthcare system in South Africa. Consequently, our objective was to examine the direct medical costs of both approaches from a public provider perspective to provide future guidance.

A prospective observational study undertaken at a leading public hospital in South Africa based principally on patients’ notes and costs from nationally procured lists. A micro-costing approach was used to estimate health care costs among adult patients with ESRD who had received either HD and PD for at least 3 months.

The majority of patients (35 percent) were aged 40 to 50 years. Patients aged 29-39 years were mostly on HD (28 percent) while those between 51-59 years mostly on PD (29 percent), with HD typically managed in the private sector with limited facilities in the public sector. The average age of patients on HD and PD was 41 and 42 years respectively. Variable costs (USD 20, 488.79) were the highest cost component for PD patients with fixed costs the highest component for HD patients ((USD 16,231.45). The annual cost of HD (USD 31,993.12) was higher than PD (USD 25,282 per patient) but not statistically significant (p = 0.816). The overall burden if appreciably more patients with ESRD are managed appropriately within the public system (covering 80 percent of the population) would be considerable and become unaffordable.

HD costs more than PD. These cost estimates are useful for carrying out future health economic analyses and for allocating greater resources to prevent progress to ESRD.

As part of a national aging and technology network, AGE-WELL, one work group aims to promote the understanding of potential policy and regulatory hurdles among innovators and decision-makers. This study describes the development of resources to help innovators to navigate policy and regulatory systems to have their technologies adopted.

A policy primer was created that highlights considerations for innovators during the innovation process (from development to implementation). The content of the policy primer was developed by identifying resources through the Canadian Agency for Drugs and Technology in Health Grey Matters search tool, and in consultation with legal and regulatory consultants. By surveying AGE-WELL technology-developing projects (n=15) we characterized the technologies being developed within the network. Survey questions included: intended end-user/purchaser of the technology and past/anticipated facilitators/barriers in their innovation process. The policy primer and survey data were combined to create tailored innovation maps with considerations for each technology being developed within the network. These materials were used to develop a beta website where users can receive information relevant to various innovation stages, as it pertains to their technology. We gained feedback about our materials via surveys and interviews with AGE-WELL technology developers.

The tailored innovation maps and website were seen as helpful resources for understanding policy and regulatory processes required for technology adoption. Technology developers expressed interest in gaining further access to these resources. Innovators desired additional resources about demonstrating value and measuring technology effectiveness.

Resources were developed to help guide technology innovators through policy and regulatory processes; preliminary feedback suggests these were valued by innovators. Next steps include refining the website and releasing these resources to innovators beyond the AGE-WELL Network.

Hospital mangers need information for decision making (1). Hospital-based health technology assessment (HTA) methods were tested out to support the budget planning of investments for a new building to be constructed for diagnostic and teaching units at a publicly funded tertiary care university hospital. The hospital board nominated an ad hoc working group to reassess all investment proposals for devices, equipment and furniture for the diagnostic or teaching units that intended to move into the new building. The need for assessment was obliged when the submitted proposals of the units exceeded two-fold the initially allocated investment budget.

Depending on the level of expenditure, all proposals were assessed by one of the following processes: (i) Proposals over EUR250,000 were evaluated by three to five person expert groups using multi-domain assessment adapting Hospital-based HTA-principles; (ii) Proposals between EUR50,000 and EUR250,000 were returned to the units for miniHTA-assessments by clinicians who submitted the initial proposals and (iii) All proposals below EUR50,000 were prioritized by the units to cut the expenditure by at least 25 percent, with a special emphasis on synergistic use of devices and equipment among the units.

The expert groups suggested significant reductions to the proposals, including the withdrawal of a Magnetic Resonance Imaging (MRI)-unit considered to be suboptimally located. Furthermore, the need for a new scanner was declined by promoting adherence to evidence-based diagnostic guidelines and more efficient utilization of existing scanners. Self-assessed MiniHTAs revealed proposals that were unnecessary or the specifications for devices needed re-adjustments. Prioritization revealed excess numbers of devices, for instance the number of cold storage appliances could be reduced. Altogether, the investment proposals were cut by over EUR3.8 million to reach the initial budgetary allocation.

Innovative and flexible usage of hospital-based HTA methodology can be applied to budget planning and evaluation of investment proposals to support decision making. Based on encouraging results, hospital-based HTA was accepted to become a part of hospital strategy as a tool for the annual investment planning.

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.

The Health Technology Assessment International (HTAi) community recognises the importance of including patients’ views from published research and systematically obtaining input from patient organizations (POs). The HTAi's Patients and Public Involvement Subgroup has elaborated the Patient Group Submission Template for HTA (HTA Template) to facilitate the collection of evidence from patients via POs involvement. In 2015 AGENAS outlined a procedure to involve POs and tested the HTA Template within a Health Technology Assessment (HTA) report on dialysis.

The HTAi template was translated into Italian and adapted to the HTA report's specific information needs: to understand patients’ experiences with different dialysis modalities and any delivery problems at the regional level. Some questions were reformulated, others were cut and two different versions of the template were used. One was tailored to POs representatives and the other to individual patients selected with a purposive sampling procedure. We provided the HTA Template to POs appointed by an umbrella organization, Cittadinanzattiva, for their input and to identify other relevant POs to be involved. We identified a list of four associations, based on geographical location and typology of patients. Each POs representative completed the first template and administered the second one to, at least one patient for each five dialysis modalities. AGENAS staff provided support on a cascade basis POs collected and returned all templates.

Researchers performed a thematic analysis of the answers received and this input was introduced in the HTA report within the chapter on Patients Aspects. Patients’ experiences closely corresponded to the ones in our qualitative literature's systematic review. However, PO representatives templates revealed an important problem of equity in access to different dialysis modalities across regions that we highlighted in the HTA report's recommendations.

One of the template's limitations was related to self-administration. In some cases, a lack of familiarity with communicating one's views in writing may have affected the survey's informative power. This pilot also demonstrated the need for a more inclusive involvement procedure, as some important POs were not initially represented by the umbrella organization.