Health technology assessment and innovation: here to help or hinder?

Innovative health technologies offer much to patients, clinicians, and health systems. Policy makers can, however, be slow to embrace innovation for many reasons, including a less robust body of evidence, perceived high costs, and a fear that once technologies enter the health system, they will be difficult to remove. Health technology funding decisions are usually made after a rigorous health technology assessment (HTA) process, including a cost analysis. However, by focusing on therapeutic value and cost-savings, the traditional HTA framework often fails to capture innovation in the assessment process. How HTA defines, evaluates, and values innovation is currently inconsistent, and it is generally agreed that by explicitly defining innovation would recognize and reward and, in turn, stimulate, encourage, and incentivize future innovation in the system. To foster innovation in health technology, policy needs to be innovative and utilize other HTA tools to inform decision making including horizon scanning, multicriteria decision analysis, and funding mechanisms such as managed agreements and coverage with evidence development. When properly supported and incentivized, and by shifting the focus from cost to investment, innovation in health technology such as genomics, point-of-care testing, and digital health may deliver better patient outcomes. Industry and agency members of the Health Technology Assessment International Asia Policy Forum (APF) met in Taiwan in November 2023 to discuss the potential of HTA to foster innovation, especially in the Asia region. Discussions and presentations during the 2023 APF were informed by a background paper, which forms the basis of this paper.

HTA capacity building in Asia: towards one goal.

OBJECTIVES: The aim of the 2022 Health Technology Assessment International (HTAi) Asia Policy Forum (APF) was to discuss experiences and challenges around health technology assessment (HTA) capacity building for both HTA agencies and companies in the Asia region and to identify possible solutions as part of a capacity building roadmap. METHODS: Discussions during the 2022 APF, informed by a pre-meeting survey of HTA agencies and industry attendees from the region, form the basis of this paper. RESULTS: HTA is an essential element of priority-setting in healthcare; however, the scarcity of skilled technical HTA practitioners is a rate-limiting step in the conduct of HTA. The lack of investment in HTA and the political will to mandate the use of HTA in decision-making may be due to a lack of understanding of the value of the HTA process, and how HTA is interpreted and used in the healthcare decision-making process. CONCLUSIONS: Increased demand for HTA is created when the value of HTA is recognized. HTA capacity-building challenges may be mitigated by educating stakeholders, particularly policymakers, on the value of, and the need to invest in, HTA as a transparent process to ensure equitable access to health care for all. Investigating a means of funding and implementing an HTA intern program between agencies, in partnership with industry, to facilitate a supportive environment to foster HTA skills and knowledge, build capacity or strengthen existing capacity should be a priority.

"What's Keeping Me Up at Night?" Reflections on the COVID-19 Pandemic in Asia.

OBJECTIVES: The 2021 Health Technology Assessment International (HTAi) Asia Policy Forum (APF) aimed to explore the challenges and opportunities presented by the global COVID-19 pandemic for health systems and industry in the Asia region, to discuss how HTA changed during the pandemic, and what its role may be moving forward into a postpandemic era. METHODS: Discussions during the virtual 2021 APF, informed by a premeeting survey of HTA agencies and industry attendees from the region describing their experience during the pandemic, form the basis of this paper. RESULTS: During the pandemic, regulatory approval for COVID-related technologies was fast-tracked with fewer evidentiary requirements, and little or no HTA being conducted before these technologies were implemented in health systems in the region. "Living HTA" incorporating real-world evidence (RWE) as it was generated became part of the HTA landscape. In comparison, non-COVID technologies experienced regulatory approval and HTA delays. A major concern of APF members was future pandemic preparedness, and to ensure that lessons are learned from COVID-19. Governments need to continue to invest in innovation and allow early regulatory approvals with the increased use of RWE. Capacity building was identified as a key investment, including capacity in HTA, modeling, as well as local production of necessary supplies and equipment. Finally, collaboration at all levels of the health system was viewed as vital. CONCLUSIONS: Post-COVID, different forms of HTA must be embraced as part of the new HTA landscape in addition to increased intra- and intercountry collaboration across all sectors of the health system, including regulatory bodies.

Sustainability of healthcare systems in Asia: exploring the roles of horizon scanning and reassessment in the health technology assessment landscape.

OBJECTIVES: The 2019 Health Technology Assessment International (HTAi) Asia Policy Forum (HAPF) discussed the role of horizon scanning (HS) and health technology reassessment (HTR) in supporting sustainable healthcare in Asia. METHODS: Discussions and presentations at the 2019 HAPF, informed by a literature review, results of a premeeting survey, and case studies of HTA agencies from the region form the basis of this paper. RESULTS: Five of the fourteen HTA agencies surveyed have established or are developing HS systems (HSSs), and six reported some experience with HTR. Although there were many differences in the respective HSSs, all were proactive and identified technologies within a 1-3-year time horizon. Commonalities included the criteria used to prioritize the technologies including burden and rarity of the disease, and cost to the health system and patients. Experience in HTR was not as extensive with most HTR activity being conducted on an ad hoc basis. Challenges for both HS and HTR include a lack of HTA capacity and good quality data, as well as a need for transparency and collaboration with industry. CONCLUSIONS: With developing universal health care and HTA capacity in many countries in Asia, HS and HTR are in their infancy. Whilst several countries in the region are experienced in all facets of HTA, other countries are developing their HTA skill base. As such, there was a clear appetite for setting up a collaborative network in the Asia region to facilitate information sharing around HTA activities, and more specifically, HS and HTR methodologies, experiences, and assessments.

Improving Access to High-Cost Technologies in the Asia Region.

OBJECTIVES: Discussions at the Health Technology Assessment International (HTAi) Asia Policy Forum (HAPF) aimed to understand the meaning of "high-cost technologies," and to explore mechanisms to increase access to these technologies in publicly funded health systems in the Asia region. METHODS: Discussions and presentations at the 2018 HAPF, informed by a literature review and a premeeting survey of HTA agencies and industry, form the basis of this paper. RESULTS: Challenges payers in the public health system face when investing in high-cost technologies include a lack of data, especially real-world data, affordability, and the budgetary impact of high-cost technologies. Managed entry schemes (MES) are one means to enable earlier access to high-cost technologies, or at reduced cost to the system. Most countries surveyed had used an MES to introduce a new health technology and most industry representatives had experience with financial-based MES, such as discounts or rebates, with most put in place to increase access to pharmaceuticals. Little experience of outcome-based or evidence-generation MES was reported. CONCLUSIONS: Although it is early days in the implementation of MES in Asia, they have the potential to play an important role enabling access to new, mainly pharmaceutical, health technologies. The development of a "road map" of MES in the region should outline the intent and need for a MES, articulating the "rules of engagement" for all stakeholders-patients, providers, payers, and industry-which will assist countries to clearly identify the problem trying to be solved, and how an MES can be part of the solution.

OVERCOMING THE BARRIERS TO ACHIEVING UNIVERSAL HEALTH CARE IN THE ASIAN REGION.

OBJECTIVES: The Health Technology Assessment International (HTAi) Asia Policy Forum (HAPF) met to discuss the challenges of achieving universal health care (UHC) in Asia. METHODS: Group discussions and presentations at the 2017 HAPF, informed by a background paper, including a literature review and the results of pre-meeting surveys of health technology assessment (HTA) agencies and industry, formed the basis of this article. RESULTS: Affordability was identified as the greatest barrier to establishing UHC; however, other impediments include the lack of political will to implement UHC, and the cultural issue of deference to expert opinion instead of evidence-based assessments. Although HTA was identified as an important prioritization tool when adding new technologies to benefit packages, it is used inconsistently in the region, resulting in a less transparent decision-making process for stakeholders. Although regional challenges exist around real-world data (RWD), including a lack of capacity to enable information and data sharing, most policy or funding decision makers in the region have access to data. However, there appears to be a disconnect with the experience of industry, whose representatives identify the lack of RWD as their primary issue. To overcome these issues, both HTA agencies and industry agree that collaboration and transparency should be fostered to support the development of robust evidence generation in the region. CONCLUSIONS: There is a willingness for HTA agencies and industry to collaborate to develop HTA methodology for the prioritization of technologies in the Asia region that support healthcare systems to achieve the ultimate outcome of UHC.

Phase 3 adaptive trial design options in treatment of complicated urinary tract infection.

New antimicrobial drugs for treatment of complicated urinary tract infection (cUTI) are generally assessed in randomized, double-blind, noninferiority clinical trials. Robust historical data for the active comparator inform on treatment effect estimation, yet typically do not substitute for the active comparator data in the proposed trial. We report design options for a phase 3 trial of cUTI using a Bayesian hierarchical model and historical data from 2 well-executed phase 3 registrational trials of doripenem. The methodology is directly applicable to other phase 3 noninferiority settings. In addition to the research design application, we provide a novel methodology for assessing the robustness of type I error control. The model borrows heavily from the prior data when the current active comparator parameter estimate approximated the historical estimate. In contrast, the model had restricted borrowing when the 2 estimates were very different. The alternative trial design, with or without the inclusion of futility stopping criteria, provides a framework for future cUTI phase 3 trials.

Community-Acquired Pneumonia Case Validation in an Anonymized Electronic Medical Record-Linked Expert System.

An electronic anonymized patient portal analysis using radiographic reports and admission and discharge diagnoses had sensitivity, specificity, positive predictive value, and negative predictive value of 84.7%, 78.2%, 75%, and 87%, respectively, for community-acquired pneumonia validated against a blinded expert medical review. This approach can help to track antimicrobial use and resistance.

Platelet-rich plasma: a case study for the identification of disinvestment opportunities using horizon scanning.

Objective This paper discusses the potential for horizon scanning to identify low-value, inappropriate clinical practices that deliver minimal benefit to patients and represent a considerable financial burden on the health system. Methods Platelet-rich plasma (PRP) was identified by routine horizon scanning as a potentially innovative treatment alternative for osteoarthritis of the knee. A rapid, non-systematic assessment of the evidence pertaining to the safety and effectiveness of PRP compared with nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of osteoarthritis of the knee was conducted. Results The evidence base supporting the use of PRP for the treatment of osteoarthritis was poor. No comparative studies were identified that compared the use of PRP to NSAIDs, the current treatment option for osteoarthritis of the knee in Australia. Despite the lack of effectiveness evidence, the use of PRP injections was rapidly increasing in the private sector using an inappropriate Medicare Benefits Schedule item number. Conclusions This assessment highlights the potential of using established horizon scanning methodologies to identify targets for full or partial disinvestment of ineffective, inefficient or harmful clinical practices. What is known about the topic? PRP is rapidly diffusing in the private health system in Australia, however the use of a Medicare Benefits Schedule item number meant that this practice was being subsidised by the public reimbursement of treatment fees. What does this paper add? Traditional horizon scanning tends to identify technologies for health systems to invest in. The evidence on the effectiveness of PRP was examined with the purpose of exploring investment in an innovative treatment that may have reduced the number of invasive procedures being performed in the public hospital system. The current evidence base does not support the use of PRP injections for the treatment of osteoarthritis. It does, however, support the use of horizon scanning as an inexpensive methodology to identify possible disinvestment targets associated with potential patient harm and high health service expenditure. What are the implications for practitioners? Practitioners should be aware that public funding for the injection of PRP should not be used for the treatment of osteoarthritis.

Systematic Review and Meta-Analysis To Estimate Antibacterial Treatment Effect in Acute Bacterial Skin and Skin Structure Infection.

A systematic literature review and meta-analysis were conducted to estimate the antibacterial treatment effect for linezolid and ceftaroline to inform on the design of acute bacterial skin and skin structure infection (ABSSSI) noninferiority trials. The primary endpoints included an early clinical treatment response (ECTR) defined as cessation of lesion spread at 48 to 72 h postrandomization and the test-of-cure (TOC) response defined as total resolution of the infection at 7 to 14 days posttreatment. The systematic review identified no placebo-controlled trials in ABSSSI, 4 placebo-controlled trials in uncomplicated skin and soft tissue infection as a proxy for placebo in ABSSSI, 12 linezolid trials in ABSSSI, 3 ceftaroline trials in ABSSSI, and 2 trials for nonantibacterial treatment. The ECTR rates at 48 to 72 h and corresponding 95% confidence intervals (CI) were 78.7% (95% CI, 61.1 to 96.3%) for linezolid, 74.0% (95% CI, 69.7 to 78.3%) for ceftaroline, and 59.0% (95% CI, 52.8 to 65.3%) for nonantibacterial treatment. The early clinical treatment effect could not be estimated, given no available placebo or proxy for placebo data for this endpoint. Clinical, methodological, and statistical heterogeneity influenced the selection of trials for the meta-analysis of the TOC treatment effect estimation. The pooled estimates of the TOC treatment response were 31.0% (95% CI, 6.2 to 55.9%) for the proxy for placebo, 88.1% (95% CI, 81.0 to 95.1%) for linezolid, and 86.1% (95% CI, 83.7 to 88.6%) for ceftaroline. The TOC clinical treatment effect estimation was 25.1% for linezolid and 27.8% for ceftaroline. The antibacterial treatment effect estimation at TOC will inform on the design and analysis of future noninferiority ABSSSI clinical trials.

Tuberculin skin test and QuantiFERON-TB Gold In-tube Test for latent tuberculosis in Thai HIV-infected adults.

BACKGROUND AND OBJECTIVE: Limited data exist for the performance of QuantiFERON-TB Gold In-tube Test (QFT-IT) in comparison to tuberculin skin test (TST) for detecting latent tuberculosis (LTB) in patients with human immunodeficiency virus (HIV) infection from tuberculosis (TB)-endemic Asia-Pacific countries. METHODS: A cohort study of Thai HIV-infected patients without history of TB or LTB treatment was conducted from March 2012 through March 2013. Each patient underwent simultaneous TST and QFT-IT. RESULTS: Among the 150 enrolled subjects, the median age was 40 years (range 17-65), 53% were male, and the median CD4 count was 367 cells/µL (range 8-1290). Reactive TST and positive QFT-IT were 16% and 13%, respectively, with low concordance between tests (kappa = 0.26); correlation between TST reaction size and level of interferon-γ was moderate (r = 0.34). Independent factors associated with discordant results were long-term smoking (adjusted odds ratio (aOR) 5.74; P = 0.002) for TST-reactive, QFT-IT-negative subjects, and age greater than 52 years (aOR 5.56; P = 0.02) and female gender (aOR 4.40; P = 0.04) for TST non-reactive, QFT-IT-positive subjects. The level of agreement between both tests improved when using a TST cut-off of ≥ 10 mm (kappa = 0.39). CONCLUSIONS: In our setting where QFT-IT is available but has limited use due to cost, TST with a cut-off of 10 mm for reactivity should be the initial LTB test. HIV-infected women and persons older than 52 years with non-reactive TST and long-term smokers with reactive TST may benefit from subsequent QFT-IT.

Content analysis of Australian direct-to-consumer websites for emerging breast cancer imaging devices.

OBJECTIVE: To describe the nature and frequency of information presented on direct-to-consumer websites for emerging breast cancer imaging devices. DESIGN: Content analysis of Australian website advertisements from 2 March 2011 to 30 March 2012, for three emerging breast cancer imaging devices: digital infrared thermal imaging, electrical impedance scanning and electronic palpation imaging. MAIN OUTCOME MEASURES: Type of imaging offered, device safety, device performance, application of device, target population, supporting evidence and comparator tests. RESULTS: Thirty-nine unique Australian websites promoting a direct-to-consumer breast imaging device were identified. Despite a lack of supporting evidence, 22 websites advertised devices for diagnosis, 20 advertised devices for screening, 13 advertised devices for prevention and 13 advertised devices for identifying breast cancer risk factors. Similarly, advertised ranges of diagnostic sensitivity (78%-99%) and specificity (44%-91%) were relatively high compared with published literature. Direct comparisons with conventional screening tools that favoured the new device were highly prominent (31 websites), and one-third of websites (12) explicitly promoted their device as a suitable alternative. CONCLUSIONS: Australian websites for emerging breast imaging devices, which are also available internationally, promote the use of such devices as safe and effective solutions for breast cancer screening and diagnosis in a range of target populations. Many of these claims are not supported by peer-reviewed evidence, raising questions about the manner in which these devices and their advertising material are regulated, particularly when they are promoted as direct alternatives to established screening interventions.

Systematic review and meta-analysis of antimicrobial treatment effect estimation in complicated urinary tract infection.

Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations.

A systematic review of elastography, electrical impedance scanning, and digital infrared thermography for breast cancer screening and diagnosis.

The objective of this study aimed to systematically identify and evaluate all the available evidence of safety, effectiveness and diagnostic accuracy for three emerging classes of technology promoted for breast cancer screening and diagnosis: Digital infrared thermal imaging (DITI), electrical impedance scanning (EIS) and elastography. A systematic search of seven biomedical databases (EMBASE, PubMed, Web of Science, CRD, CINAHL, Cochrane Library, Current Contents Connect) was conducted through March 2011, along with a manual search of reference lists from relevant studies. The principal outcome measures were safety, effectiveness, and diagnostic accuracy. Data were extracted using a standardised form, and validated for accuracy by the secondary authors. Study quality was appraised using the quality assessment of diagnostic accuracy studies tool, while heterogeneity was assessed using forest plots, Cooks' distance and standardised residual scatter plots, and I (2) statistics. From 6,808 search results, 267 full-text articles were assessed, of which 60 satisfied the inclusion criteria. No effectiveness studies were identified. Only one EIS screening accuracy study was identified, while all other studies involved symptomatic populations. Significant heterogeneity was present among all device classes, limiting the potential for meta-analyses. Sensitivity and specificity varied greatly for DITI (Sens 0.25-0.97, Spec 0.12-0.85), EIS (Sens 0.26-0.98, Spec 0.08-0.81) and ultrasound elastography (Sens 0.35-1.00, Spec 0.21-0.99). It is concluded that there is currently insufficient evidence to recommend the use of these technologies for breast cancer screening. Moreover, the high level of heterogeneity among studies of symptomatic women limits inferences that may be drawn regarding their use as diagnostic tools. Future research employing standardised imaging, research and reporting methods is required.

Access to antiretroviral therapy during excess black-water flooding in central Thailand.

Excess black-water flooding in central Thailand resulted in closure of several healthcare facilities in the Fall of 2011. Persons living with human immunodeficiency virus (HIV) infection were presumably at risk for interruption of antiretroviral therapy (ART), with consequent treatment failure. We conducted a retrospective cohort study of ART use among patients in care at a Thai HIV clinic that closed due to excess flood water. Among 217 patients on ART who had clinic appointments within the one-month interval before the floods through the one-month interval after the clinic re-opened, seven (3%) reported non-sustained ART access. Non-sustained ART access was independently associated with prior low self-reported ART adherence (P<0.001) and less than six-months duration on the ART regimen (P=0.03). Advanced ART receipt or procurement at other flood-free healthcare facilities were strategies associated with ART access. During a flood disaster, identification and close monitoring of at-risk patients, patient-staff communication, flood preparedness plans, "HIV care access for all" policies, and collaboration among patients, healthcare providers and the government are relevant issues within preparedness plans to optimize ART access.

Postflood pseudofungemia due to Penicillium species.

We report an outbreak investigation of fungemia due to Penicillium species after prolonged flooding of a Thai hospital. Contaminated rubber diaphragms of blood culture bottles were identified, and the pseudo-outbreak was resolved after environmental cleaning, use of high-efficiency particulate air filtration, and strict compliance with basic infection control practices for blood culture procurement.

The high comorbidity burden of the hepatitis C virus infected population in the United States.

BACKGROUND: Chronic hepatitis C (HCV) disease can be complicated with comorbid conditions that may impact treatment eligibility and outcomes. The aim of the study was to systematically review comorbidities and symptoms in an HCV infected population, specifically assessing comorbidities associated with HCV anti-viral treatment and disease, as well as comparing comorbidities between an HCV infected and uninfected control population. METHODS: This was a retrospective cohort study within a United States medical claims database among patients with chronic HCV designed to estimate the two-year period prevalence of comorbidities. Patients with two HCV diagnosis codes, 24 months of continuous health insurance coverage, and full medical and pharmacy benefits were included. RESULTS: Among a chronic HCV cohort of 7411 patients, at least one comorbid condition was seen in almost all patients (> 99%) during the study period. HCV-infected patients reported almost double the number of comorbidities compared to uninfected controls. Of the 25 most common comorbidities, the majority of the comorbidities (n = 22) were known to be associated with either HCV antiviral treatment or disease. The five most frequent comorbidities were liver disease [other] (37.5%), connective tissue disease (37.5%), abdominal pain (36.1%), upper respiratory infections (35.6%), and lower respiratory disease (33.7%). Three notable comorbidities not known to be associated with antiviral treatment or disease were benign neoplasms (24.3%), genitourinary symptoms & ill-defined conditions (14.8%), and viral infections (13.8%). CONCLUSIONS: This US medically insured HCV population is highly comorbid. Effective strategies to manage these comorbidities are necessary to allow wider access to HCV treatment and reduce the future burden of HCV disease and its manifestations.

Over 150 potentially low-value health care practices: an Australian study.

OBJECTIVE: To develop and apply a novel method for scanning a range of sources to identify existing health care services (excluding pharmaceuticals) that have questionable benefit, and produce a list of services that warrant further investigation. DESIGN AND SETTING: A multiplatform approach to identifying services listed on the Australian Medicare Benefits Schedule (MBS; fee-for-service) that comprised: (i) a broad search of peer-reviewed literature on the PubMed search platform; (ii) a targeted analysis of databases such as the Cochrane Library and National Institute for Health and Clinical Excellence (NICE) "do not do" recommendations; and (iii) opportunistic sampling, drawing on our previous and ongoing work in this area, and including nominations from clinical and non-clinical stakeholder groups. MAIN OUTCOME MEASURES: Non-pharmaceutical, MBS-listed health care services that were flagged as potentially unsafe, ineffective or otherwise inappropriately applied. RESULTS: A total of 5209 articles were screened for eligibility, resulting in 156 potentially ineffective and/or unsafe services being identified for consideration. The list includes examples where practice optimisation (ie, assessing relative value of a service against comparators) might be required. CONCLUSION: The list of health care services produced provides a launchpad for expert clinical detailing. Exploring the dimensions of how, and under what circumstances, the appropriateness of certain services has fallen into question, will allow prioritisation within health technology reassessment initiatives.