Now showing 1 - 10 of 23
  • Publication
    Challenges in Cost-Effectiveness Analysis Modelling of HPV Vaccines in Low- and Middle-Income Countries: A Systematic Review and Practice Recommendations
    Background: Low- and middle-income countries (LMICs) face a number of challenges in implementing cervical cancer prevention programmes that do not apply in high-income countries. Objective: This review assessed how context-specific challenges of implementing cervical cancer prevention strategies in LMICs were accounted for in existing cost-effectiveness analysis (CEA) models of human papillomavirus (HPV) vaccination. Methods: The databases of MEDLINE, EMBASE, NHS Economic Evaluation Database, EconLit, Web of Science, and the Center for the Evaluation of Value and Risk in Health (CEA) Registry were searched for studies published from 2006 to 2015. A descriptive, narrative, and interpretative synthesis of data was undertaken. Results: Of the 33 studies included in the review, the majority acknowledged cost per vaccinated girl (CVG) (26 studies) and vaccine coverage rate (21 studies) as particular challenges for LMICs, while nine studies identified screening coverage rate as a challenge. Most of the studies estimated CVG as a composite of different cost items. However, the basis for the items within this composite cost was unclear. The majority used an assumption rather than an observed rate to represent screening and vaccination coverage rates. CVG, vaccine coverage and screening coverage were shown by some studies through sensitivity analyses to reverse the conclusions regarding cost-effectiveness, thereby significantly affecting policy recommendations. Conclusions: While many studies recognized aspects of the particular challenges of HPV vaccination in LMICs, greater efforts need to be made in adapting models to account for these challenges. These include adapting costings of HPV vaccine delivery from other countries, learning from the outcomes of cervical cancer screening programmes in the same geographical region, and taking into account the country’s previous experience with other vaccination programmes.
    Scopus© Citations 20  13
  • Publication
    Cost-effectiveness evidence on approved cancer drugs in Ireland: the limits of data availability and implications for public accountability
    Background: We surveyed evidence published by Ireland’s National Centre for Pharmacoeconomics (NCPE) on the cost-effectiveness of cancer drugs approved for funding within the Irish public healthcare system. The purpose is threefold: to assess the completeness and clarity of publicly available cost-effectiveness data of such therapies; to provide summary estimates of that data; to consider the implications of constraints on data availability for accountability regarding healthcare resource allocation. Methods: The National Cancer Control Programme lists 91 drug-indication pairs approved between June 2012 and July 2020. Records were retrieved from the NCPE website for each drug-indication pair, including, where available, health technology assessment (HTA) summary reports. We assessed what cost-effectiveness data regarding approved interventions is available, aggregated it and considered the consequences of reporting constraints. Results: Among the 91 drug-indication pairs 61 were reimbursed following full HTA, 22 after a rapid review process and 8 have no corresponding NCPE record. Of the 61 where an HTA report was available, 41 presented costs and quality-adjusted life-year (QALY) estimates of the interventions compared. Cost estimates and corresponding incremental cost-effectiveness ratios (ICERs) are based on prices on application for reimbursement. Reimbursed prices are not published. Aggregating over the drug-indication pairs for which data is available, we find a mean incremental health gain of 0.85 QALY and an aggregate ICER of €100,295/QALY, which exceeds Ireland’s cost-effectiveness threshold of €45,000/QALY. Conclusion: Reimbursement applications by pharmaceutical manufacturers for cancer drugs typically exceed Ireland’s cost-effectiveness threshold, often by a considerable margin. On aggregate, the additional total net cost of new drugs relative to current treatments needs to be more than halved for the prices sought on application to be justified for reimbursement. Commercial confidentiality regarding prices and cost-effectiveness upon reimbursement compromises accountability regarding the fair and efficient allocation of scarce healthcare resources.
    Scopus© Citations 1  7
  • Publication
    Risk Stratification in Cost-Effectiveness Analyses of Cancer Screening: Intervention Eligibility, Strategy Choice, and Optimality
    (SAGE Publications, 2021-10-11)
    Introduction: There is increasing interest in risk-stratified approaches to cancer screening in cost-effectiveness analysis (CEA). Current CEA practice regarding risk stratification is heterogeneous and guidance on the best approach is lacking. This article suggests how stratification in CEA can be improved. Methods: I use a simple example of a hypothetical screening intervention with 3 potential recipient risk strata. The screening intervention has 6 alternative intensities, each with different costs and effects, all of which vary between strata. I consider a series of alternative stratification approaches, demonstrating the consequences for estimated costs, effects, and the choice of optimal strategy. I supplement this analysis with applied examples from the literature. Results: Adopting the same screening policy for all strata yields the least efficient strategies, where efficiency is understood as the volume of net health benefit generated across a range of cost-effectiveness threshold values. Basic stratification that withholds screening from lower-risk strata while adopting a common strategy for those screened increases efficiency. Greatest efficiency is achieved when different strata receive separate strategies. While complete optimization can be achieved within a single analysis by considering all possible policy combinations, the resulting number of strategy combinations may be inconveniently large. Optimization with separate strata-specific analyses is simpler and more transparent. Despite this, there can be good reasons to simulate all strata together in a single analysis. Conclusions: If the benefits of risk stratification are to be fully realized, policy makers need to consider the extent to which stratification is feasible, and modelers need to simulate those choices adequately. It is hoped this analysis will clarify those policy and modeling choices and therefore lead to improved population health outcomes.
    Scopus© Citations 3  6
  • Publication
    Magnetic Tweezers-Based Force Clamp Reveals Mechanically Distinct apCAM Domain Interactions
    Cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) play a crucial role in cell-cell interactions during nervous system development and function. The Aplysia CAM (apCAM), an invertebrate IgCAM, shares structural and functional similarities with vertebrate NCAM and therefore has been considered as the Aplysia homolog of NCAM. Despite these similarities, the binding properties of apCAM have not been investigated thus far. Using magnetic tweezers, we applied physiologically relevant, constant forces to apCAM-coated magnetic particles interacting with apCAM-coated model surfaces and characterized the kinetics of bond rupture. The average bond lifetime decreased with increasing external force, as predicted by theoretical considerations. Mathematical simulations suggest that the apCAM homophilic interaction is mediated by two distinct bonds, one involving all five immunoglobulin (Ig)-like domains in an antiparallel alignment and the other involving only two Ig domains. In summary, this study provides biophysical evidence that apCAM undergoes homophilic interactions, and that magnetic tweezers-based, force-clamp measurements provide a rapid and reliable method for characterizing relatively weak CAM interactions.
      464Scopus© Citations 17
  • Publication
    Dealing with Time in Health Economic Evaluation: Methodological Issues and Recommendations for Practice
    Time is an important aspect of health economic evaluation, as the timing and duration of clinical events, healthcare interventions and their consequences all affect estimated costs and effects. These issues should be reflected in the design of health economic models. This article considers three important aspects of time in modelling: (1) which cohorts to simulate and how far into the future to extend the analysis; (2) the simulation of time, including the difference between discrete-time and continuous-time models, cycle lengths, and converting rates and probabilities; and (3) discounting future costs and effects to their present values. We provide a methodological overview of these issues and make recommendations to help inform both the conduct of cost-effectiveness analyses and the interpretation of their results. For choosing which cohorts to simulate and how many, we suggest analysts carefully assess potential reasons for variation in cost effectiveness between cohorts and the feasibility of subgroup-specific recommendations. For the simulation of time, we recommend using short cycles or continuous-time models to avoid biases and the need for half-cycle corrections, and provide advice on the correct conversion of transition probabilities in state transition models. Finally, for discounting, analysts should not only follow current guidance and report how discounting was conducted, especially in the case of differential discounting, but also seek to develop an understanding of its rationale. Our overall recommendations are that analysts explicitly state and justify their modelling choices regarding time and consider how alternative choices may impact on results.
      10Scopus© Citations 56
  • Publication
    Expanding health technology assessment towards broader value: Ireland as a case study
    Healthcare innovations often represent important improvements in population welfare, but at what cost, and to whom? Health technology assessment (HTA) is a multidisciplinary process to inform resource allocation. HTA is conventionally anchored on health maximization as the only relevant output of health services. If we accept the proposition that health technologies can generate value outside the healthcare system, resource allocation decisions could be suboptimal from a societal perspective. Incorporating broader value in HTA as derived from social values and patient experience could provide a richer evaluative space for informing resource allocation decisions. This article considers how HTA is practiced and what its current context implies for adopting broader value to evaluating health technologies. Methodological challenges are highlighted, as is a future research agenda. Ireland serves as an example of a healthcare system that both has an explicit role for HTA and is evolving under a current program of reform to offer universal, single-tier access to public services. There are various ways in which HTA processes could move beyond health, including considering the processes of care delivery and/or expanding the evaluative space to some broader concept of well-being. Methods to facilitate the latter exist, but their adaptation to HTA is still emerging. We recommend a multi-stakeholder working group to develop and advance an international agenda for HTA that captures welfare/benefit beyond health.
  • Publication
    A Systematic Review of Cost-Effectiveness Analyses of Colorectal Cancer Screening in Europe: Have Studies Included Optimal Screening Intensities?
    Objective: To assess the range of strategies analysed in European cost-effectiveness analyses (CEAs) of colorectal cancer (CRC) screening with respect to the screening intervals, age ranges and test cut-offs used to define positivity, to examine how this might influence what strategies are found to be optimal, and compare them with the current screening policies with a focus on the screening interval. Methods: We searched PubMed, Web of Science and Scopus for peer-reviewed, model-based CEAs of CRC screening. We included studies on average-risk European populations using the guaiac faecal occult blood test (gFOBT) or faecal immunochemical test (FIT). We adapted Drummond’s ten-point checklist to appraise study quality. Results: We included 39 studies that met the inclusion criteria. Biennial screening was the most frequently used interval which was analysed in 37 studies. Annual screening was assessed in 13 studies, all of which found it optimally cost-effective. Despite this, 25 of 26 European stool-based programmes use biennial screening. Many CEAs did not vary the age range, but the 14 that did generally found broader ranges optimal. Only 11 studies considered alternative FIT cut-offs, 9 of which found lower cut-offs superior. Conflicts between current policy and CEA evidence are less clear regarding age ranges and cut-offs. Conclusions: The existing CEA evidence indicates that the widely adopted biennial frequency of stool-based testing in Europe is suboptimal. It is likely that many more lives could be saved throughout Europe if programmes could be offered with more intensive annual screening.
  • Publication
    Adherence to Discounting Guidelines: Evidence from Over 2000 Published Cost-Effectiveness Analyses
    Previous studies have shown that not all cost-effectiveness analyses (CEAs) adhere to recommended guidelines on intertemporal discounting. This analysis investigates adherence in a sample of over 2000 CEAs from seven countries. Guideline discount rates were retrieved for Australia, Belgium, Canada, Ireland, The Netherlands, New Zealand and the UK. Data on the rates applied in published CEAs were retrieved from the Tufts CEA Registry from the sample countries within the periods covered by the discounting guidelines. The relationship between adherence and candidate explanatory factors were assessed using logistic regression. The analysis appraised 2270 CEAs. The overall rate of adherence to discounting recommendations was 79%. Country-specific adherence ranged from 28% in New Zealand to 87% in Belgium and the UK. Adherence in Australia and Canada was 73% and 66%, respectively. Adherence is statistically significantly higher in more recent studies, countries currently applying differential discounting and manufacturer-sponsored studies. Relative to the reference case of Australia, adherence is statistically significantly higher in the UK and lower in Canada and New Zealand. There is notable variation in the rates of adherence to discounting recommendations between countries and over time. Incomplete adherence raises concerns regarding the comparability of evidence between studies. In turn, this raises concerns regarding equity of access to scarce healthcare resources. Journal editors should ensure that adherence to discounting recommendations is assessed as part of the peer review process.
    Scopus© Citations 3  13
  • Publication
    Appropriateness of strategy comparisons in cost-effectiveness analyses of infant pneumococcal vaccination: a systematic review
    (Cambridge University Press, 2023-07-12) ; ;
    Objectives: Cost-effectiveness analysis (CEA) is the standard framework for informing the efficient allocation of scarce healthcare resources. The importance of considering all relevant intervention strategies and appropriate incremental comparisons have both long been recognized in CEA. Failure to apply methods correctly can lead to suboptimal policies. Our objective is to assess if CEAs of infant pneumococcal vaccination apply appropriate methods with respect to the completeness of strategies assessed and incremental comparisons between them. Methods: We conducted a systematic search of the PubMed, Scopus, Embase, and Web of Science databases and performed a comparative analysis of the retrieved pneumococcal vaccination CEAs. We checked the appropriateness of the incremental analyses by attempting to replicate the published incremental cost-effectiveness (CE) ratios from the reported costs and health effects. Results: Our search returned twenty-nine eligible articles. Most studies failed to recognize one or more intervention strategies (n = 21). Incremental comparisons were questionable in four CEAs and insufficient reporting of cost and health effect estimates was identified in three studies. Overall, we only found four studies that made appropriate comparisons between all strategies. Lastly, study findings appear to be strongly associated with manufacturer sponsorship. Conclusions: We found considerable scope for improvement regarding strategy comparison in the infant pneumococcal vaccination literature. To prevent overestimation of the CE of new vaccines, we urge greater adherence to existing guidelines recommending that all available strategies are evaluated to capture relevant comparators for CE evaluation. Closer adherence to existing guidelines will generate better evidence, leading to more effective vaccination policies.
  • Publication
    Colorectal Cancer Screening within Colonoscopy Capacity Constraints: Can FIT-Based Programs Save More Lives by Trading off More Sensitive Test Cutoffs against Longer Screening Intervals?
    Introduction. Colorectal cancer (CRC) prevention programs using fecal immunochemical testing (FIT) in screening rely on colonoscopy for secondary and surveillance testing. Colonoscopy capacity is an important constraint. Some European programs lack sufficient capacity to provide optimal screening intensity regarding age ranges, intervals, and FIT cutoffs. It is currently unclear how to optimize programs within colonoscopy capacity constraints. Design. Microsimulation modeling, using the MISCAN-Colon model, was used to determine if more effective CRC screening programs can be identified within constrained colonoscopy capacity. A total of 525 strategies were modeled and compared, varying 3 key screening parameters: screening intervals, age ranges, and FIT cutoffs, including previously unevaluated 4- and 5-year screening intervals (using a lifetime horizon and 100% adherence). Results were compared with the policy decisions taken in Ireland to provide CRC screening within available colonoscopy capacity. Outcomes estimated net costs, quality-adjusted life-years (QALYs), and required colonoscopies. The optimal strategies within finite colonoscopy capacity constraints were identified. Results. Combining a reduced FIT cutoff of 10 µg Hb/g, an extended screening interval of 4 y and an age range of 60–72 y requires 6% fewer colonoscopies, reduces net costs by 23% while preventing 15% more CRC deaths and saving 16% more QALYs relative to a strategy (FIT 40 µg Hb/g, 2-yearly, 60–70 year) approximating current policy. Conclusion. Previously overlooked longer screening intervals may optimize cancer prevention with finite colonoscopy capacity constraints. Changes could save lives, reduce costs, and relieve colonoscopy capacity pressures. These findings are relevant to CRC screening programs across Europe that employ FIT-based testing, which face colonoscopy capacity constraints.
    Scopus© Citations 4  7