Alzheimer’s disease (AD) is a neurodegenerative disease with progressive neuropsychiatric symptoms. Patient care is often provided by informal caregivers similarly to various other chronic diseases. This targeted literature review assessed the difference in burden experienced by caregivers of people with AD in comparison to other chronic diseases.

Two separate search strings were developed to identify (i) caregiver burden in AD and (ii) caregiver burden in other chronic diseases using PubMed. Studies published in English (January 2012-October 2022) were included. Comparison of the caregiver burden was done using the weighted mean values (MV) of several questionnaires including the Zarit Burden Interview (ZBI), a 22-item self-report questionnaire for caregivers ranging from 0 to 88 points. ZBI is stratified into four categories of caregiving burden: Little or no burden (0 to 21), mild to moderate burden (22 to 40), moderate to severe burden (41 to 60) and severe burden (61 to 88).

ZBI was the most frequently used questionnaire; 13 studies reported data on caregiver burden in AD and 39 studies reported data on 20 other chronic diseases. The caregiver burden ranged from 18 to 48 in AD, measured by ZBI. The MV of AD burden was 36 based on a total of 1,703 participants. The caregiver burden in other chronic diseases ranged from MV of 5 (chronic musculoskeletal pain) to 59 (bipolar disorder).

Measured by ZBI, AD burden on caregivers (MV: 36, range: 18-48) was greater than heart failure (MV: 27, range: 16-29) and type 2 diabetes (MV: 26, range: Not reported) but lesser than schizophrenia (MV: 56, range: 52-65) and bipolar disorder (MV: 59, range: Not reported).

AD has a significant burden on caregivers. When assessing the value of interventions targeting AD, the impact of AD on caregivers should be considered in addition to the impact of AD on patients. Further studies are required to assess the informal care burden in AD and other chronic diseases.

Non-invasive Scrambler Therapy (ST) reduces pain by attaching electrodes to neural pathways of major nerves, transmitting information along with microcurrent to the nerves to induce a painless sensation. The ST has been widely used to reduce pain for patients with musculoskeletal pain. However, little is known about the musculoskeletal pain relief effect of the ST. Therefore, this study aims to evaluate the treatment effectiveness of the ST.

A systematic literature review was conducted based on the following search strategy and databases, and all studies published before August 2021 were included in Pubmed, Embase, and Cochrane library, Ovid Medline, Koreamed, kmbase, and Science On. The subjects were patients with intractable and musculoskeletal pain, excluding cancer pain, and intervention methods included non-invasive ST alone or in combination with physical therapy. In addition, the comparative method was not limited. The outcome variables were the degree of pain relief, total analgesic use, health-related quality of life, pressure pain threshold, pain intensity and functional interference scales, and pain sensitivity. Safety-related outcome variables were all side effects. Cochrane Risk of Bias 1.0 was used to assess the risk of bias in the literature.

Two hundred forty-one articles were retrieved using a pre-determined search strategy. Of these, 15 duplicate articles, 215 articles after reviewing the abstract and title, and nine articles after checking the full text were excluded. Two studies with randomized controlled trials (RCTs) were finally selected. When comparing ST and placebo groups for musculoskeletal pain, the pain reduction effect of ST lasted for three weeks. Moreover, patients with neuropathic pain treated with ST had a lower pain intensity for one to three months compared to the drug treatment group.

Based on this systematic review, the effectiveness of ST is yet sufficient owing to small sample size and possibility of selective report bias. More studies with well-designed RCTs are required to further assess the effectiveness of the ST.

Developed in 2014, the Systematic Review (SR) Toolbox has played a critical role in helping researchers to identify appropriate tools to support systematic reviews. Since the resource was launched, the systematic review and wider evidence synthesis process has evolved considerably. The way in which the SR Toolbox originally classified tools at launch had become dated. We updated and rebuilt the SR Toolbox in 2022 underpinned by a novel taxonomy to reflect the latest review and evidence synthesis landscape.

All guidance and software tools contained within the SR Toolbox were manually extracted in February 2022. Information contained from tool records were extracted by a single reviewer into an Excel spreadsheet, with a second reviewer checking a sample. The spreadsheet was translated to a Microsoft Access database underpinned with a new taxonomy to reflect the expansion of evidence synthesis methods and new review types (or ‘families’). A brief analysis of the remapped tools was conducted to identify current gaps in software and guidance support for evidence synthesis. A new user interface was also developed.

The updated version of the SR Toolbox was launched 13 May 2022. At that time, the resource included records on 235 software tools and 112 guidance tools. Regarding ‘review families’, most software tools (n = 223) and guidance documents (n = 78) were applicable to supporting systematic reviews. Fewer software (n = 66) and guidance (n = 22) tools were applicable to reviews of reviews, while qualitative reviews were less served by guidance documents (n = 19). In terms of ‘review stages’, most guidance documents were associated with quality assessment (n = 70), while most software was related to searching (n = 84) and synthesis (n = 82). To-date, there is a lack of software (n = 2) and guidance (n = 3) tools to support stakeholder engagement.

The SR Toolbox has received a significant update to ensure that tools are classified and shared based on the latest systematic review and evidence synthesis methods. As part of the update, analysis of the contents of the toolbox highlighted potential gaps in tool support for certain review types/stages.

The first direct-acting antiviral (DAA) therapies for chronic Hepatitis C virus (HCV) infection were reimbursed via Australia’s Pharmaceutical Benefits Scheme (PBS) in March 2016. This was based on the recommendation from the Pharmaceutical Benefits Advisory Committee (PBAC) that the regimens would be acceptably cost-effective at an incremental cost-effectiveness ratio (ICER) of AUD15,000/quality-adjusted life-year (QALY). Broad access to DAA therapies has been a key strategy in driving a national health goal to eliminate viral hepatitis as a major health threat by 2030. Since the initial PBS listings for DAA therapies and subsequent listings of newer DAA treatments such as Maviret, the demographics and disease characteristics of currently treated patients have markedly changed. The aim of our analysis was to reassess the cost-effectiveness of Maviret, accounting for the changes of the treated population characteristics and retreatment in first-line failures and reinfected individuals.

To assess the cost-effectiveness six years after initial listing of Maviret, an update was made to the Markov model used to achieve PBS reimbursement for Viekira-Pak® in May 2016. Amendments to the Viekira-Pak model include: changes to baseline age and fibrosis distribution of treated patients, and incorporation of retreatment of first-line failures (those not achieving a sustained virologic response (SVR)) and reinfected individuals. Treatment-related inputs including SVR response rates, adverse events, treatment-related disutility and discontinuations were sourced from pivotal glecaprevir/pibrentasvir clinical trials.

Using the published price of Maviret, the ICER is above AUD15,000/QALY but well below the commonly used ICER threshold in other chronic diseases (AUD45,000/QALY). When the confidential effective price is used, the ICER is under the AUD15,000/QALY cost-effectiveness threshold set by the PBAC for DAA therapies.

Despite substantial changes to the population seeking treatment in Australia since reimbursement in 2016, Maviret remains a cost-effective treatment for chronic HCV infection.

Chronic Kidney Disease (CKD) is a condition that leads to end-stage renal disease (ESRD), characterized by a gradual loss of kidney function. In 2021, the healthcare system expenditure of CKD in Australia was estimated to be over AUD2.3 billion (USD1.5 billion), largely attributed to Kidney Replacement Therapy (KRT, dialysis or kidney transplantation). This exploratory analysis aims to calculate the cost-benefit to the Australian healthcare system should KRT be delayed.

The prevalence of ESRD with and without KRT between 2016 and 2021 was estimated, and a simple linear regression model was created to estimate the prevalence of ESRD with KRT between 2022 and 2026. The projected cost of KRT management in 2022 was calculated, enabling an approximate cost benefit presented as the number of patients needed to reduce expenditure by AUD1 million (USD0.7 million).

In 2021, it was calculated that 34,554 patients live with ESRD in Australia, of which 28,542 patients are on KRT. The number of new patients on KRT increases linearly by an average of 943 patients per year and provided a model with a strong goodness-of-fit (R2 = 0.99); predicting that the prevalence of patients on KRT is estimated to increase to 33,417 patients by 2026. Dialysis accounts for the highest cost associated with ESRD management, estimated to be AUD87,975/year/patient (USD58,253), and accounts for over AUD1.3 billion (USD0.9 billion) in annual expenditure. When considering the proportion of patients receiving KRT undergoing dialysis (52.6%), first-year renal transplant (3.4%), and post-kidney transplantation (43.9%), in 2022, the average annual cost per patient receiving KRT is estimated to be AUD57,565 (USD38,109). The prevention of KRT in 17.4 patients in 2022, decreasing to 15.4 patients in 2026, has the potential to save AUD1 million/year (USD0.7 million).

The prevalence of ESRD in Australia increases linearly and contributes to a significant cost to the Australian healthcare system. In 2022, preventing KRT in 17.4 patients (0.06%) can equate to a saving of AUD1 million/year (USD0.7 million), further decreasing to 15.4 patients (0.05%) in 2026.

An estimated 17.9 million people died from cardiovascular diseases (CVDs) in 2019, which is 32 percent of all global deaths and 85 percent were due to heart attack and stroke. Chest pain is one of the most common reasons for presenting to the emergency department (ED). It is increasingly recognized that artificial intelligence (AI) will have a significant impact on the practice of medicine in the near future and may help with diagnosis and risk stratification. We aim to estimate a diagnostic prediction of acute myocardial infarction by the development and validation of an AI model.

Data on 134 variables of 3,986 consecutive patients who presented to the ED with non-traumatic chest pain were included in the analysis. Using AI tools, a neural network model was developed to establish the risk of acute myocardial infarction (AMI) to achieve n=150 patients over 18 years of age attending the ED.

The mean age was 65.5 (±13.7) years and 63.6 percent were male. Most (60.1%) patients were admitted to hospital, with only 20.3 percent diagnosed at hospital discharge with ischemic heart disease (IHD). All patients were followed up for two months, and 6.3 percent were readmitted to the ED, but none presented with an episode of IHD. In the data analysis of the entire sample we obtained a probability of diagnosing IHD by the SmartHeart model (S=93.1%, E=47.3%, PPV=31.0%, and NPV=96.4%). When we analyzed the sample of patients with no history of IHD (n=104), the diagnosis accuracy was as follows (S=100%, E=77.5%, PPV=42.8%, and NPV=100%).

Our AI model provides information to predict patients who are suffering from acute IHD. AI has been reported to outperform emergency physicians and current risk stratification tools to diagnose IHD, but has rarely been integrated into practice. This study highlights the diagnostic applicability and accuracy of this type of tool and that is why studies should be implemented to see its effectiveness in routine practice in EDs.

Currently, no cure exists for the 1 in 2,500 Australian babies born with potentially fatal cystic fibrosis (CF). The authors conducted a health technology assessment (HTA) case study analysis of all regulatory approved CF treatments in Australia from January 1994 to July 2022. Submissions were also made under the Therapeutics Goods Administration and Pharmaceutical Benefits Advisory Committee (TGA-PBAC) parallel process.

Public summary and source materials were researched to understand relevant clinical and health economic evidence requirements, and access decisions from Australia’s lead HTA body, PBAC.

The review found that there are more than seven approved products in Australia. Of those, all four novel CF transmembrane conductance regulator (CFTR) modulating medications, which treat the underlying disease, received an orphan drug designation and were eventually listed. However, initial HTA decisions were mixed, with one recommended (25%), one not recommended (25%), and two deferred (50%). Clinical efficacy, cost-effectiveness, clinical need, as well as patient/carer-centric perspectives were most influential in HTA recommendations. Like other rare disease treatments, price, high incremental cost-effectiveness ratios (ICERs), uncertainty around cost-effectiveness and/or efficacy were key barriers to positive decisions. Notably, Australian stakeholders did not recommend CF medicines when their ICERs significantly exceeded a threshold of AUD200,000 (USD134,700) per quality-adjusted life year (QALY) gained. Administratively, Australia addresses risks associated with poor cost-effectiveness and high costs through managed access programs, risk-sharing agreements (RSA) and special pricing arrangements.

Recently approved elexacaftor-tezacaftor-ivacaftor would be inaccessible to many Australian patients without inclusion in the Pharmaceutical Benefits Scheme (PBS); this placement increases access by limiting patients’ payments to AUD42.50 (USD28.62) maximum per prescription. Alternatively, manufacturers of therapies for other chronic or rare life-threatening conditions can participate in Australia’s Highly Specialised Drugs Program and/or Life Saving Drugs Program to facilitate access.

Companies can accelerate and optimize market access by using the TGA-PBAC parallel process. Other Asia-Pacific countries can model components of Australia’s approach to advancing access to innovative, live-saving therapies.

Robot-assisted surgery is one of the minimally invasive surgical approaches that has been increasingly utilized across a wide range of surgeries. However, there is limited evidence of robotic-assisted thoracic surgery (RATS) for patients with lung cancer. This study aims to evaluate the safety and effectiveness of RATS in lung cancer patients compared with video-assisted thoracoscopic surgery (VATS) and open thoracotomy.

A comprehensive search for studies that compared RATS versus VATS or open thoracotomy published until 12 April 2022, was conducted. Two review authors independently assessed studies for inclusion and risk of bias, and extracted data. We used results of reported perioperative outcomes, oncological outcomes, and survival outcomes. When more than two studies contributed data, meta-analyses were performed.

Four randomized controlled trials (RCT) were included. Firstly, three RCTs comparing RATS with VATS were identified. Compared with the VATS group, the RATS group had significantly lower blood loss, more harvested lymph nodes and lymph node stations. However, there were no significant differences in operative time, transfusion rates, hospital stay, drainage duration, reoperation, readmission, postoperative pain, and postoperative complications. Survival outcomes were not reported. Secondly, one RCT comparing RATS with open thoracotomy was identified. Compared with open thoracotomy group, the RATS group had significantly lower blood loss, less postoperative pain, and shorter chest drainage duration. On the other hand, there were no significant differences in operative time, hospital stay, postoperative complications, number of harvested lymph nodes and lymph node stations, and survival outcomes (disease-free survival, overall survival).

Evidence on the effectiveness and safety of RATS compared with VATS or open thoracotomy for lung cancer is of low certainty, but we suggest that RATS is a feasible and safe alternative to conventional thoracic surgeries for lung cancer patients on the basis of current data. Additionally, more and better studies are required to provide evidence on the benefits and cost-effectiveness of RATS.

Chronic pain is a debilitating condition with a high burden of disease. Neurostimulation therapy is an established modality for patients with chronic pain refractory to pharmacological based approaches and conservative interventional therapies. The therapy has evolved over the decades, based on improved understanding of the mechanisms of action, as well as technological advancement in device design.

Our objective is to conduct a review of the innovation in neurostimulation therapy for chronic pain, in the context of health technology assessment (HTA), and its implications on policies related to patient access.

A qualitative literature review was conducted to identify published HTAs, systematic reviews, clinical guidelines and other relevant articles and reports on neurostimulation therapies used in pain management. Searches were limited to the past 10 years to ensure that a contemporary analysis was conducted.

Our review indicates that there has been continuous innovation in neurostimulation therapies for chronic pain. This includes improvements in battery longevity and reduced size, advances in the design of leads, the development of novel stimulation waveforms and personalized programming using sophisticated algorithms including sensing and feedback loops, and remote management to name a few. Clinical research has also enabled an expansion in the range of neural targets and indicated subpopulations. The literature shows that apart from reduction in pain, neurostimulation therapy facilitates improvements in the quality of life, and reduction in opioid dependence, carer burden and disability, which are outcomes important to patients as well as to society at large. Clinical guidelines are largely supportive of neurostimulation for the management of chronic refractory pain in carefully selected patients.

The range and complexity of neurostimulation devices and the variety of study designs presents a challenge for evidence synthesis. HTA bodies need to ensure that the methodologies for evaluating a heterogeneous therapy such as neurostimulation for pain management are robust, and that the policies for determining access to such innovative therapies are patient-centric and fit-for-purpose.

Spinal cord stimulation (SCS) is an effective and safe option for patients with refractory neuropathic pain, with positive health technology assessment (HTA) recommendations across Western Europe, yet SCS uptake remains low. Estimating target patient populations within HTAs may impact upon medical device uptake, pricing and access. However, there is a dearth of information on how this is typically conducted. This study aimed to compare the approaches of Western Europe HTA agencies for estimating the target population for SCS.

A survey was conducted among members of the Health Economics and Reimbursement function from Western Europe to collect country-specific information on how HTA agencies assess the target population of medical devices (MD). The estimations of the target population for SCS were extracted from HTA publications and compared.

Eight Health Economics and Reimbursement (HER) Analysts from France, Germany, the United Kingdom (UK), Belgium, Spain, Italy, Sweden and Norway completed the survey. HTA Agencies in France, UK and Belgium routinely ask for epidemiological data in the manufacturer submission, whereas in Germany, Sweden and Norway the request is dependent on the type of HTA submission. All HTA agencies, except NICE (UK), perform an independent estimation of the target population. HTA agencies in Germany and UK typically use epidemiological data from industry. In all countries, the estimation of the target population may indirectly impact the price of the MD, especially when budget impact analysis indicates a potential high use of healthcare resources. Only France, Belgium and UK have published HTA recommendations about SCS, however the estimated target population, nor the number of patients with refractory neuropathic pain, is not always included. Only the French and UK HTA agencies publish an approximation of the target population for SCS using the number of patients implanted every year.

This study showed there is a lack of harmonization between Western European HTA agencies’ guidelines on the inclusion and estimation of target patient populations. The new EU HTA Regulation should help to address this situation.

Phelan-McDermid syndrome (PMS) is a chromosomal disorder caused by the loss of the end of chromosome 22, that is manifested as a neurodevelopmental disorder. Providing an adapted version of a guideline was seen as essential, as currently, there are no such booklets based on an international guideline for PMS patients, families and caregivers. The European Reference Networks (ERN) Guidelines programme results from a call for proposals funded (DG SANTE/2018/B3/030) for the development of Clinical Practice Guidelines (CPG) and Clinical Decision Tools in the area of rare diseases. Based on this European consortium, the purpose of this study is to describe how two Spanish HTA agencies, OSTEBA-BIOEF (Basque Office for Health Technology Assessment) and AETSA (Andalusian Health Quality Assessment Department) methodologically support the ERN-ITHACA (Rare malformation syndromes and rare intellectual and neurodevelopmental disorders) in the development of a comprehensive patient booklet based on a CPG to be used as an adjunct in the management of PMS syndrome that will be published in 2023.

A preliminary booklet was created by HTA agencies using the new European guideline for PMS and a Dutch guideline. The booklet structure is an adaptation based on a European Commission template with the guidance of the methodological Handbook#11.

Through a comprehensive adaptation, following the PMS guideline and the Handbook #11, a booklet is developed for the PMS patients. Composed by 28 pages in DIN A5 format were introduction, diagnosis, treatment, pregnancy, do’s, supportive care, social networks (including a QR code) and a glossary are included. The selection of a symbol, colors at a chromatic level, a typography and graphical elements as illustrations were created as a corporate identity. Clinical experts and patient representatives that have participated in the creation of the guideline will assess and validate the booklet.

Collaboration between agencies, clinicians and patients is critical to obtain evidence-based products adapted to the needs of patients and people involved in their care.

Positron emission tomography combined with computed tomography (PET/CT) using 11C-methionine (11C-MET) is used to detect astrocytomas and low-grade brain tumors, in the primary detection of all malignant and benign neoplasms of the central nervous system (CNS), and in order to monitor staging and evaluate the results of treatment.

To assess the clinical and economic effectiveness of PET/CT with the use of radiopharmaceutical drugs (RFLP) based on 11C-MET in the diagnosis of CNS neoplasms, a systematic review of literature by keywords in the Pubmed/MEDLINE database was conducted. The search result was 218 publications. The analysis included 21 publications that met the search criteria, including three meta-analyses and six systematic literature reviews.

Diagnostic efficacy in distinguishing gliomas of high and low malignancy has moderate diagnostic accuracy (combined sensitivity and specificity were 80% and 72%, respectively), but higher sensitivity compared to Fludeoxyglucose F18 (18F-FDG). PET/CT with 11C-MET demonstrated good diagnostic value in detecting brain tumor recurrence (combined sensitivity and specificity of 92% and 87%, respectively) compared with 18F-FDG.

PET/CT diagnostics of CNS neoplasms using the drug 11C-MET is an innovative technology with greater specificity and sensitivity than 18F-FDG, positively influences the subsequent surgery plan and identifies tumors previously undetermined by magnetic resonance imaging (MRI), CT or PET/CT with 18F-FDG.

Around 90 percent of hospitalized patients require vascular access devices (VADs) during hospitalization to administer fluids, medications and facilitate blood transfusions. After insertion, it is essential to maintain VADs to achieve optimal dwell time and reduce complications. Flushing of VADs is an integral part of catheter maintenance practices. With increasing cost burden on healthcare systems and nursing shortages, it is crucial to use time-and cost-saving technologies such as pre-filled flush syringes for common procedures namely VAD maintenance. This study aims to compare the clinical and economic impact of using pre-filled saline syringes versus manually-prepared saline syringes for flushing VADs in Korea.

A budget impact analysis was developed using Microsoft Excel to estimate the annual clinical and economic impact of pre-filled saline syringes and a base case scenario of flushing 100,000 VADs was modeled. Clinical impact was estimated for peripheral intravenous catheter (PIVC) failure, central line-associated bloodstream infections (CLABSIs), central line occlusion and nurse time. Economic impact was estimated for costs associated with flushing materials, additional length of stay (LOS) due to CLABSI, VAD replacement, and nurse-time. Global and local data sources were used for inputs. Assumptions include: (i) Distribution of 95 percent peripheral and 5 percent central VADs; (ii) 50 percent peripheral and 50 percent central VADs on intermittent therapy; and (iii) 3 flushes/catheter-day.

Over a one-year timeframe, the model estimated 3,344 fewer PIVC failures, 15 fewer CLABSIs and 157 fewer occlusions with adoption of pre-filled saline syringes. Nurse time was reduced by 3,465 hours. Potential net annual savings from lower device cost, reduced complications, shortened LOS and increased nurse efficiency were estimated to be KRW23.7 million (USD178,957).

Using pre-filled saline syringes instead of manually-prepared syringes for flushing VADs may result in fewer complications, lower VAD utilization, nurse time saving and cost savings in Korea. This can potentially help improve patient outcomes, relieve nurses’ stress to some extent and help healthcare decision-makers to reallocate these cost savings to other life-saving technologies.

A peripherally inserted central catheter (PICC) is an important vascular access device to administer certain intravenous (IV) therapies, which is traditionally placed using fluoroscopy in radiology suites. With advancing tip-confirmation technology, PICCs can be placed at the patient bedside by nurses, without any delays arising from wait time for the radiology suite or the need of transferring patients to the radiology suite, leading to time savings and allowing prompt start to IV therapy. This study aims to estimate the cost and time impact of placing PICCs at the bedside using tip-confirmation technology led by nurses versus in the radiology suite using fluoroscopy by radiologists.

A budget impact analysis was developed using Microsoft Excel to estimate the annual impact of inserting PICCs at the bedside versus in the radiology suite. The base case scenario was modelled for 1,000 PICCs placed in a private Australian hospital. Impact on bed days, labor time and overall cost was estimated by using global and local data sources for inputs. It was assumed that 100 percent PICC are placed in a radiology suite in current practice, while 95 percent are placed at the bedside and 5 percent in the radiology suite in future practice.

By shifting PICC insertion to the bedside using tip-confirmation technology, the model estimated a reduction of labor time by 221 hours and bed days by 113 days. Despite an increase in the cost of consumables by AUD34,041 (USD22,760) and reduction of Medicare Benefits Schedule rebate by AUD260,730 (USD174,328), overall cost savings of AUD1.01million (USD675,660) was observed due to significant savings due to the t reduced utilization of the radiology suite.

PICC insertion at the patient bedside using tip-confirmation technology by nurses may lead to time and cost savings as compared to placing them in the radiology suite. This can help alleviate the burden on radiology suites and reduce their wait times, potentially leading to timely treatment initiation and discharge. Since PICCs at the bedside are typically placed by specialized vascular access nurses, these cost savings can be redirected to employ and train them.

A high proportion of patients with end-stage kidney disease (ESKD) are treated with hemodialysis (HD). To lower morbidity and maintain overall cost control in patients with ESKD, it is crucial for health systems to establish and maintain durable hemodialysis (HD) access. Our objective was to assess the budget impact of utilizing the ‘WavelinQ Endo Arteriovenous Fistula (AVF) system’ (WavelinQ) for HD patients.

A one-year economic model from the Hospital (Flinders Medical Centre, FMC) perspective was developed with Australian epidemiological and costing data. Clinical data were collected from real-world sources. The incident (n=50) and prevalent (n=250) cohorts were based on FMC utilization patterns. The current standard of care was surgical AVF (sAVF) and/or central venous catheters (CVC). With introduction of WavelinQ into practice, the substitution rate was set at 50 percent in new patients and ten percent amongst existing patients. Index procedure and reinterventions costs for the patient were based on the weighted average cost using National Efficient Price Determination 2020 to 21. Total costs preWavelinQ introduction were compared to post WavelinQ substitution to determine the budget impact.

Based on FMC expected patient cohort and WavelinQ substitution rates, the mean annual cost savings per incident and prevalent patient were AUD26,873 and AUD3,549, respectively, which lead to overall mean annual cost savings per patient of AUD7,437. The calculated per patient additional upfront cost of AUD7,010 with the WavelinQ index procedure versus sAVF was more than offset by the savings due to less post-procedure reinterventions. Overall, at the assumed substitution rates with WavelinQ, the model predicted a cost saving of approximately AUD2.2 million dollars for FMC.

The use of WavelinQ is expected to lead to cost savings of AUD2.2 million dollars from the FMC perspective. Hospitals should consider not just the increase in upfront costs but also potential savings from less reintervention procedures. There is a need for continued research on the budget impact of different HD modalities across multiple settings.

Most new drugs have only clinical studies focused on a single population at the time of first registration, hence their indications for use are restricted to this population. For clinical conditions when there are no other treatments available, new drugs have higher costs in Brazil. There is no review of prices when these medications broaden their therapeutic areas, and this can have a significant financial impact. This study’s objective is to assess the financial implications of pembrolizumab’s incremental indication after its initial registration.

We calculated the annual cost to treat all Brazilian patients with indications for use in the first registration and all incremental indications of pembrolizumb. Populations were estimated by epidemiological data from the pembrolizumab clinical trials called, KEYNOTE studies, and the INCA 2023 cancer estimate for the Brazilian population. Costs were calculated by CMED-ANVISA price value and considering the dosing of 200mg every 3 weeks.

In 2016, pembrolizumab was granted registration in Brazil was restricted to patients with advanced melanoma. In 2022 the indication was expanded to more than 20 new indications, with several studies in progress that potentially will lead to further inclusions. The estimate of patients eligible for indications increase of 1,796 to 99,544 patients with an increased total cost from BRL625,802,837 to BRL34,685,366,192 (USD121,185,677.4 to USD6,716,763,399.04).

The financial burden of pembrolizumab’s expanded uses after it was first approved could significantly rise, endangering the long-term viability of healthcare systems. In Brazil, where medicine costs are not regularly monitored, the annual inflation adjustment is the only factor that causes prices to change. In order to lower medicine prices in response to the addition of new indications, the expansion of therapeutic options for the same condition, or even obsolescence, regulations are required.

Clinically significant cytomegalovirus infection (CSI-CMV) is an important factor associated with mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). It is estimated that the incidence of CSI-CMV in the post-HSCT period is 30 percent to 70 percent in transplanted individuals. Therefore, CSI-CMV is considered a complication in allogeneic HSCT, which can trigger Cytomegalovirus disease (CMVD). Letermovir is an antiviral agent indicated especially for the prophylaxis of CMVD post-HSCT. The objective of this work was to evaluate the efficacy, effectiveness and safety of letermovir, comparing it with placebo or other existing prophylactic treatments.

A systematic review was carried out according to PRISMA 2020. A strategy was developed for searching electronic bibliographic databases. Retrieved publications were selected by a pair of reviewers. The same pair performed the data extraction. A qualitative assessment of the efficacy, effectiveness and safety of letermovir was performed.

Eighteen studies were included, being experimental and observational. Overall, the pivotal RCT demonstrates the efficacy of letermovir in reducing the incidence of CSI-CMV. However, there was no statistically significant difference in all-cause mortality and letermovir-related overall survival, events of graft versus host disease, neutropenia, acute kidney disease and 48-week mortality. Observational studies, in general, present results similar to those found in the pivotal RCT. The main adverse events associated with letermovir were peripheral edema (14.5%), vomiting (18.5%), headache (13.9%), cough (14.2%), abdominal pain (11.8%) and fatigue (13.4%).

The prophylactic use of letermovir in CMV-R+ patients after allogeneic HSCT demonstrates beneficial results in the prevention of CSI-CMV. However, there were no identified improvements for other outcomes. As for safety, it was observed that there is still little information about adverse events related to the drug, and studies assessing this aspect are needed for better comprehension.

The organizational impact (OI) of new technologies is becoming a major driver for our healthcare systems and for modernizing the care pathway for the benefit of users and professionals. Some technologies give rise to a reorganization of the healthcare system, particularly in the case of connected medical devices.

The Medical Device Committee at Haute Autorité de Santé (HAS) appraises medical devices (MD) in view of their reimbursement by the French health insurance scheme. The Committee’s evaluation criteria take account of the therapeutic benefit of the MD and its public health benefit. OI-related aspects are frequently claimed by health technology developers (HTD) in their MD submission dossiers. However, this aspect is rarely documented. Therefore, guidance explaining how HTD should support and structure any claim of an OI was needed.

This work was based on the HAS OI Map for Health Technology Assessment published in 2020, the analyses of specific HAS opinions, hearings with concerned stakeholders (HTD, service providers and patients), and a committee meeting focused on OI.

The HTD guide for MD submission was updated with guidance to support OI claims. For each claimed OI, the HTD should identify the criterion corresponding to the most relevant OI, the indicator to describe each selected criterion, the stakeholders concerned, and the data to be provided. The choice of method is according to the OI: if the indicator is measurable, data from validated measurement tools are expected. If not, especially in cases where the use of the MD requires a specific organization before its deployment, the absence of data must be justified and a detailed impact analysis is necessary. In this case, the development plan for the demonstration of the OI is needed.

With this updated guide for HTDs, claimed OI dimension shall be better supported in future MD dossiers submitted to HAS in view of their reimbursement in France.

According to the most recent definition health technology assessment (HTA) “is a multidisciplinary process that uses explicit methods to determine the value of a health technology at different points in its lifecycle. The purpose is to inform decision-making in order to promote an equitable, efficient, and high-quality health system”. This article aimed to evaluate implementation of HTA in decision making in the Balkan countries.

A scoping review of the existing literature took place to locate relevant scientific articles, policy papers and documents released by the respective Ministries. We searched data for 6 Western Balkan countries (Albania, Bosnia and Herzegovina, Kosovo, Montenegro, North Macedonia and Serbia) and didn’t focus on those countries that are part of the European Union (EU). For the literature search key words were used, while documents only in English were included in the analyses. Additionally, the search was conducted for the period January 2010 until October 2022.

The Western Balkan countries are in process of integration to the EU and based on this they are trying to make improvement in different sectors including health services. However, the use of HTA in most of the studied countries is in its preliminary phase. Most of the countries have established HTA bodies or specific authorities but with limited resources (both human and financial). Additionally, their reports are non-binding for policy makers and healthcare decisions are taken based on experts’ opinions and not an extensive HTA analyses.

Despite their efforts, the Western Balkan countries need to improve and considerably increase the use of HTA in decision-making. Its use can help in provision of better healthcare services as well as to decrease costs. Specific attention should be put on human and financial resources that are lacking in all settings.

Western Balkan countries need to put much more efforts for harmonization of their legal framework with that of the EU countries.

In the development and update process of clinical practice guidelines (CPG) is necessary to focus research questions as much as possible to optimize the systematic reviews. We carried out a scoping review as a precursor to a systematic review to update the recommendation of a CPG for the Management of Patients with Autism Spectrum Disorders in Primary Care. To our knowledge, there is limited information in the existing literature on graphical options for visually presenting scales or other available instruments and classification in a timeline graph.

We conducted a systematic search to identify instruments for screening of neurodevelopmental disorders and early detection and diagnosis of autism spectrum disorder (ASD). All studies were analyzed to retrieve scales and other instruments used in the assessment of neurodevelopment in the preschool children, and detection of signs and symptoms of neurodevelopment disorder or ASD. We developed a timeline graphic to compile all of the instruments retrieved.

The information about the name of instrument, type, age of application, diagnostic accuracy, and context of validation was transferred to spreadsheet of the software program Microsoft Excel in tabular format. The instruments found were finally categorized according to the role of each of them in the diagnostic of autism, and age in which they are used. We developed a timeline graph for visually presenting classified instruments according to utility in the routine developmental surveillance, detection of specific signs and symptoms of ASD and diagnostics and evaluation of autism.

The proposed graphical timeline could assist methodologists and researchers in identifying gaps of evidence and lines of research related to use and validation in different contexts the scales and other instruments actually developed. The process of review of evidence can provide information useful for future research in the context of primary research. The relationship between groups of work of health technology assessment and primary research promote the knowledge transfer and optimization of research.