Australian Pharmaceutical Benefits Advisory Committee Research Articles

HTA10 Bring out Your Dead: A Review of the Cost Minimization Approach in Health Technology Assessment Submissions to the Australian Pharmaceutical Benefits Advisory Committee

Published literature has levied a barrage of criticism against the cost-minimization approach to economic evaluation for new medicines. The prevailing papers on the topic has declared its ‘death’. However, the approach is the primary means by which new medicines are listed for public subsidy in Australia. The Pharmaceutical Benefits Advisory Committee (PBAC), which assesses new medicines for public subsidy, maintain Methodology Guidelines that indicate when the approach would be acceptable. While these Methods Guidelines establish requirements for cost-minimization that is theoretically robust and avoid the issues identified in the literature, adherence to these Methods Guidelines has not been assessed. This research aims to explore the factors that influence the PBAC recommendation for subsidy of new medicines that use a cost-minimization approach to economic evaluation, including adherence to the Methodology Guidelines.

Overview of Health Technology Assessment Processes for Time-Limited Recommendations


 Several regulatory agencies have implemented processes to facilitate timely access to innovative therapies for patients with rare or life-threatening diseases with high unmet medical needs, typically with additional data-generation requirements to address important uncertainties in the existing evidence base at the time of regulatory approval. Many health technology assessment (HTA) agencies have adapted their processes to include time-limited recommendations (TLRs) for such therapies, which allows patients access to these medications while additional data are collected to verify the clinical efficacy, real-world effectiveness, or economic value of the new therapeutic. The objective of this Environmental Scan is to identify what HTA agencies have processes in place for TLRs and to describe these processes, if applicable.
 HTA agencies in North America, Europe, Australia, and New Zealand were considered for this report based on commonalities to the Canadian context in terms of geography and relevant regulatory or HTA and reimbursement processes. Seven HTA agencies (the National Institute for Health and Care Excellence, the Scottish Medicines Consortium, France’s Haute Autorité de Santé, the Dutch National Health Care Institute, the Italian Medicines Agency, the Belgium National Institute for Health and Disability Insurance, and the Australian Pharmaceutical Benefits Advisory Committee) that have implemented formal TLR processes, through managed entry agreements, special access funds, or other related programs were identified. Most TLR programs are referred to as managed access or entry agreements, but other types include interim acceptance, conditional inclusion, assessment contingent on additional evidence development, and additional specialized programs or pathways.
 TLRs are primarily used for promising (and sometimes high-cost) medicines intended to treat a condition with an important unmet medical need; some specify that the disease must be serious and life threatening (regardless of prevalence), others indicate that the process is used for orphan drugs intended to treat rare conditions, and others consider multiple criteria or do not have prerequisite criteria for eligible indications.
 Evidence generation requirements for TLRs vary across HTA agencies and are often dependent on the nature of the clinical and economic uncertainties identified in the initial assessment; sources include later follow-up from ongoing clinical trials, new clinical trials, real-world data, or a combination of both clinical and real-world studies. Additionally, most TLR processes have explicit maximum durations for the time-limited period, which range from 2 to 7 years across the included HTA agencies (although some allow for time adjustments or renewals); however, the French and Scottish HTA agencies determine the duration of the time-limited period on a case-by-case basis.
 Overall, this report provides an overview of HTA processes for TLRs across HTA agencies in Europe and Australia, many of which may be useful to inform the implementation of future TLR processes in Canada, as well as to refine existing ones.

Health technology assessments and real-world evidence: tell us what you want, what you really, really want.

Health technology assessments and real-world evidence: tell us what you want, what you really, really want.

POSA301 A Review of Pharmaceutical Benefits Advisory Committee (PBAC) Public Summary Documents to Investigate the Use of Child-Specific Utility Measures in Decision Making in Australia

Methods for valuing health-related quality-of-life (HRQoL) are accepted for use in the general population but use of these methods is more challenging in children (aged under eighteen). In this study, we investigated the use of HRQoL measures for medicines used by children by reviewing Public Summary Documents released by the Australian Pharmaceutical Benefits Advisory Committee (PBAC), where a cost-utility analysis was performed.

Surrogate Endpoints in Health Technology Assessment: An International Review of Methodological Guidelines.

In the drive towards faster patient access to treatments, health technology assessment (HTA) agencies are increasingly faced with reliance on evidence from surrogate endpoints, leading to increased decision uncertainty. This study undertook an updated survey of methodological guidance for using surrogate endpoints across international HTA agencies. We reviewed HTA and economic evaluation methods guidance from European, Australian and Canadian HTA agencies. We considered how guidelines addressed the methods for handling surrogate endpoints, including (1) level of evidence, (2) methods of validation, and (3) thresholds of acceptability. Across the 73 HTA agencies surveyed, 29 (40%) had methodological guidelines that made specific reference to consideration of surrogate outcomes. Of the 45 methods documents analysed, the majority [27 (60%)] were non-technology specific, 15 (33%) focused on pharmaceuticals and three (7%) on medical devices. The principles of the European network for Health Technology Assessment (EUnetHTA) guidelines published in 2015 on the handling of surrogate endpoints appear to have been adopted by many European HTA agencies, i.e. preference for final patient-relevant outcomes and reliance on surrogate endpoints with biological plausibility and epidemiological evidence of the association between the surrogate and final endpoint. Only a small number of HTA agencies (UK National Institute for Care and Excellence; the German Institute for Medical Documentation and Information and Institute for Quality and Efficiency in Health Care; the Australian Pharmaceutical Benefits Advisory Committee; and the Canadian Agency for Drugs and Technologies in Health) have developed more detailed prescriptive criteria for the acceptance of surrogate endpoints, e.g. meta-analyses of randomised controlled trials showing strong association between the treatment effect on the surrogate and final outcomes. As the decision uncertainty associated with reliance on surrogate endpoints carries a risk to patients and society, there is a need for HTA agencies to develop more detailed methodological guidance for consistent selection and evaluation of health technologies that lack definitive final patient-relevant outcome evidence at the time of the assessment.

Cost-effectiveness and financial risks associated with immune checkpoint inhibitor therapy.

The reimbursement of immune checkpoint inhibitors is challenging. Funding these technologies involves the careful balance between awarding innovation and ensuring affordability as increases in drug spending compete directly with other health care and social expenditure. This narrative review examines the recommendations of 2 health technology assessment agencies-the Australian Pharmaceutical Benefits Advisory Committee and the British National Institute of Clinical Excellence-to determine the factors that contribute to the approval and rejection of immune checkpoint inhibitors as well as the use of manage entry schemes and risk management strategies to control expenditure. Reimbursement decisions from 6 immune checkpoint inhibitor drugs (ipilimumab, pembrolizumab, nivolumab, durvalumab, atezolizumab, avelumab) covering 10 different cancers were examined. The extrapolation of survival beyond the clinical trial and lack of head-to-head evidence are some of the main issues relating to cost effectiveness. Payers managed financial risks using different mechanisms such as risk share agreements and financial caps. This review of the reimbursement decisions and subsequent financial impact in Australia and the UK suggests budgets for immune checkpoint inhibitor therapy have been well managed so far. Through risk agreements and managed entry programmes, the example of immune checkpoint inhibitor therapies illustrates that industry and payers can effectively collaborate to ensure that innovative, but expensive, drugs can be made readily available to patients.

Comparing the ICERs in Medicine Reimbursement Submissions to NICE and PBAC—Does the Presence of an Explicit Threshold Affect the ICER Proposed?

ObjectivesThe English National Institute for Health and Care Excellence (NICE) and the Australian Pharmaceutical Benefits Advisory Committee (PBAC) require evidence that a new medicine represents value for money before being publicly funded. NICE has an explicit threshold for cost effectiveness, whereas PBAC does not. We compared the initial incremental cost-effectiveness ratios (ICERs) presented by manufacturers in matched submissions to each decision-making body, with the aim of exploring the impact of an explicit threshold on these ICERs. MethodsData were extracted from matched submissions from 2005 to 2015. The ICERs in these submissions were compared within each pair and with respect to a cost-effectiveness threshold. ResultsFifty-eight pairs of matched submissions were identified. The median difference between the ICERs ($2635/quality-adjusted life year [QALY]) was significantly greater than zero (Wilcoxon signed-rank test, P = 0.0299), indicating that the proposed ICERs in the submissions to NICE were higher than those in the matched submissions to PBAC. On 93% of occasions, NICE ICERs were within –$17,772 to +$48,422 of the corresponding PBAC ones (Bland-Altman analysis), demonstrating poor agreement. When an implicit threshold of AUD$50,000/QALY was assumed for PBAC decision making, only eight pairs of submissions had discordant ICERs falling above or below the respective threshold. ConclusionsThe significantly higher ICERs in the submissions to NICE than those to PBAC may be a consequence of NICE’s explicit willingness-to-pay threshold, and/or other health system factors. Industry may be assuming an implicit threshold for PBAC when constructing their ICERs despite the lack of acknowledgement of such a threshold.

OP30 Health Technology Assessment And The Decision-Making Process Of New Drug Listing In Hong Kong

INTRODUCTION:In Hong Kong, the Drug Advisory Committee (DAC) has had the role of evaluating and advising new drugs to be included in the listing of the Hospital Authority Drug Formulary since July 2005. The drug review process was subject to challenge due to a lack of transparency to members of the public and documentation of the scientific basis for decision making. The purpose of this review was to describe the process, evaluation criteria and possible outcomes of decision making for new drugs listed in the Hong Kong Hospital Authority Drug Formulary in comparison to Health Technology Assessment (HTA) policies in overseas countries.METHODS:Details of the decision-making processes including new drug listing submissions, the DAC meeting, procedures before and after the meeting, were extracted from the official Hong Kong Hospital Authority drug formulary management website and manual. Publicly available information related to new drug decision making processes for four HTA agencies (National Institute for Health and Clinical Excellence (NICE), Scottish Medicines Consortium (SMC), Australian Pharmaceutical Benefits Advisory Committee (PBAC), and Canadian Agency for Drugs and Technologies in Health (CADTH)) were reviewed and retrieved from official documents on their public domains.RESULTS:The DAC is in charge of the systematical and critical appraisal of new drugs for listing on the formulary, reviewing submitted applications, and making decisions of drug listing based on scientific evidence in which safety, efficacy and cost-effectiveness are primary considerations. When compared to other HTA agencies, transparency of decision-making processes of the DAC, relevance of clinical and health economic evidence, and lack of health economic and methodological input to submissions were major challenges of the new drug listing policy in Hong Kong.CONCLUSIONS:Despite the challenges identifed, this review provided suggestions for establishing a more transparent, credible, evidence-based decision-making process for the Hong Kong Hospital Authority Drug Formulary. Proposals for improvement in the listing of new drugs in the formulary should be a priority in healthcare reform.

PDB44 - Prescription Data in Australia: How Useful is this ‘Big' Data?

Detailed prescription data is difficult to get access to Australia. Health care is heavily subsidised in Australia and information on government paid medical services paid including pharmaceutical scripts is collected by the Commonwealth. This abstract seeks to uncover the process with which the data can be obtained and assess its usage in terms of reimbursement submissions to the Australian Pharmaceutical Benefits Advisory Committee (PBAC). A review of previous applications to get access to prescription data was performed. Prescription data was analysed according to the current PBAC guidelines and ISPOR good practice guidelines to assess applicability for reimbursement submissions in Australia. The review of previous applications revealed that multiple steps are involved with getting access to Australian prescription data. Pharmaceutical companies can obtain data directly from the Australian Government’s Department of Human Services (DHS) but this can be a long and complicated process. Usually companies contract a third party vendor (TPV) licensed by the DHS to hold a 10% patient sample of prescription data. All requests for data or analyses must be approved by the DHS External Request Evaluation Committee. This information is used to inform current usage of reimbursed drugs as well as budget impact of new drugs. There are examples of successful attempts of getting access to 100% of prescription data for special populations. Moreover Medicare services data such as blood test and scans is also collected but not linked up with prescription data. Obtaining prescription data in Australia is not uncommon, however a rigorous process needs to be navigated and therefore people often use a TPV. Furthermore the possibility of linking Medicare services data with prescription data is exciting as it will provide possibilities for reducing uncertainty in health technology assessments with respect to health economic modelling and broader impact on health care budgets.

Health benefit assessment of pharmaceuticals: An international comparison of decisions from Germany, England, Scotland and Australia

BackgroundLittle is known on the performance of the newly introduced health benefit assessment process, AMNOG, in Germany compared to other health technology assessment agencies. ObjectiveWe analysed whether decisions of the German Federal Joint Committee (FJC) deviate from decisions of the UK National Institute for Health and Care Excellence (NICE), the Scottish Medicines Consortium (SMC) and the Australian Pharmaceutical Benefits Advisory Committee (PBAC). MethodsWe analysed decisions made for comparable patient subgroups by the four agencies between 2011 and 2014. First, decisions were compared (a) by their final outcome, i.e. whether a health benefit was identified, and (b) by the agencies’ judgement on comparative effectiveness. Subsequently, we partially explored reasons for differences between HTA agencies. ResultsFrom the 192 FJC decisions, we identified 55 that overlapped with NICE, 166 with SMC and 119 with PBAC. FJC agreed with NICE in 40% in final outcome (Cohen’s Kappa=−0.13). Similar results were obtained for FJC and SMC (47.6%, kappa=0.03) and FJC and PBAC (48.7%, kappa=0.07). Agreement increased when comparing judgements based on comparative effectiveness only. However, the FJC’s final decision was positive only in 43.6%, 39.2% and 44.5% of the patient subgroups, as opposed to 74.5% (NICE), 68.7% (SMC), and 68.9% (PBAC), respectively. ConclusionWe show that the FJC – an agency relatively new in structurally assessing the health benefit of pharmaceuticals – deviates considerably in decisions compared to other HTA agencies. Our study also reveals that the FJC tends to appraise stricter than NICE.

Pharmacoeconomics is everyone's business

To the Editor, In July 2015, I completed a week-long pharmacoeconomics summer school at Utrecht University in Holland. This course introduced me to some economic theories that allow us to relate patient and societal values to the amount of money a community should spend on drug treatments. Previously unaware of these concepts myself, they affect my work as a pharmacist every day, through access to medicines provided by the Pharmaceutical Benefits Scheme. To determine whether a drug treatment is worth spending money on, we can use pharmacoeconomic evaluations. One important consideration in health economics is opportunity cost. When a decision is made to spend money on a particular drug treatment for a patient, as a result of funding that treatment, consideration has to be given to which drug treatments cannot be funded. This concept will become increasingly pertinent, with the advent of personalised medicine and the availability of more expensive and targeted drug treatments. Pharmacoeconomic evaluations help to determine whether the money we spend on a treatment is effective, improves the quality of life for our patients and is valued by our society. Ideally, a new treatment would cost less than its comparator, and provide improved patient outcomes. Usually, a new treatment will cost more than its comparator with the trade-off of providing improved patient outcome. If a new treatment were to cost more and result in worse outcomes than its comparator, it would be an easy decision to avoid spending money on that treatment. Similarly, if a treatment was cheaper but resulted in worse outcomes, it would not be accepted by society. Pharmacoeconomic evaluations can be conducted from different perspectives; the healthcare perspective, which considers direct and indirect costs associated with treatment from within the healthcare system only. An alternative is the societal perspective, which considers direct and indirect costs both internal and external to the healthcare system, including time lost at work due to illness or the cost of attending appointments. Societal and cultural values play an important part in determining which drug treatments should be made available for the community. As an example, one aspect of health in one culture, such as independent mobility, may not be as important as another aspect of health care in another culture, such as living without pain. For this reason, care must be taken when assessing pharmacoeconomic evaluations conducted overseas for generalisability. The Australian Pharmaceutical Benefits Advisory Committee is renowned in Europe as an example of how to use pharmacoeconomic evaluations to determine which treatments should be funded by the government for access by the Australian population. These same concepts have potential to be applied locally in a smaller scale through the work of drug and therapeutics committees. Such committees work to provide governance and quality use of medicines in patients by providing access to safe and effective treatments. Drug and therapeutics committees also consider the implications of funding expensive treatments for one patient cohort, which will result in an inability of funding other treatments. I would like to acknowledge and thank the Society of Hospital Pharmacists of Australia Research and Development Grants Program for affording me the opportunity to participate in this summer school through the support of the Novartis Pharmacoeconomics Grant 2015.

Should the Lambda (λ) Remain Silent?

When making decisions regarding the funding of new health technologies (e.g. pharmaceuticals), a key consideration should be the opportunity cost associated with a positive funding decision in terms of other patients’ health. Lambda (k) is a term that has been used to refer to a maximum acceptable value (cost-effectiveness threshold) for the incremental cost-effectiveness ratio (ICER) of a new technology, which should reflect the opportunity cost of funding decisions. In 2006, Gafni and Birch [1] discussed the ‘silence of the k’ with respect to the justification of its numerical value within the decision-making process. They noted that the use of threshold values, which do not represent the true opportunity cost of new and generally more expensive technologies, can lead to increased health expenditures with little evidence of increases in population health. In this commentary, we interpret the ‘silence of the k0 with respect to the lack of explicit recognition of the use of a cost-effectiveness threshold by national funding bodies that use the threshold in the decision-making process. We also discuss the potential impact of this silence on health systems. As an example, the Australian Pharmaceutical Benefits Advisory Committee (PBAC) makes recommendations regarding the public funding of pharmaceuticals, on the basis of clinical effectiveness, safety and cost effectiveness (value for money). No official statement has ever been made about the use of a cost-effectiveness threshold to determine whether a pharmaceutical provides value for money. Although our focus is on the Australian PBAC decisionmaking process, the discussion can be applied more widely—first, to many other national funding bodies that use economic evaluation to inform funding decisions but do not explicitly acknowledge the use of a threshold, e.g. the Medical Services Advisory Committee in Australia (MSAC) or the Canadian Agency for Drugs and Technologies in Health, and second, to any collectively funded health system that fails to consider the opportunity costs of its decisions.

Assessment of the Quality of the Clinical Evidence in Submissions to the Australian Pharmaceutical Benefits Advisory Committee: Fit for Purpose?

BackgroundAssessments of the comparative clinical (and cost) effectiveness of new medicines are increasingly being used to inform decisions on their reimbursement. Assessments of added clinical benefit are invariably based on evidence generated to support registration. ObjectiveOur objective was to identify and characterize significant problems relating to the quality of the clinical evidence in submissions to the Australian Pharmaceutical Benefits Advisory Committee (PBAC) seeking subsidy on the Pharmaceutical Benefits Scheme and thus determine whether the evidence presented to the committee was “fit for purpose.” MethodsWe conducted a retrospective analysis of submissions considered by the PBAC between 2005 and 2012 using a published evaluation framework. We developed an additional framework to categorize significant problems in more detail. Significant problems related to the choice of comparator, the unavailability of randomized clinical trial evidence, poor-quality data, a claim of clinical superiority, and a claim of clinical noninferiority. ResultsWe identified 261 significant problems in 479 major submissions. There was a significant problem with the sponsor’s choice of comparator in 11% of the submissions. The most common significant problem (29%) was the determination of a medicine’s comparative performance in the target patient population. ConclusionsThe supporting clinical evidence is the foundation of a PBAC submission. We found a poor fit for purpose; on average, one in every two major submissions had a significant problem with the supporting evidence. The findings from our study, if confirmed in other jurisdictions, raise important questions regarding what clinical evidence should be generated to support the reimbursement of new medicines.

Exploring Structural Uncertainty in Model-Based Economic Evaluations

Given the inherent uncertainty in estimates produced by decision analytic models, the assessment of uncertainty in model-based evaluations is an essential part of the decision-making process. Although the impact of uncertainty around the choice of model structure and making incorrect structural assumptions on model predictions is noted, relatively little attention has been paid to characterising this type of uncertainty in guidelines developed by national funding bodies such as the Australian Pharmaceutical Benefits Advisory Committee (PBAC). The absence of a detailed description and evaluation of structural uncertainty can add further uncertainty to the decision-making process, with potential impact on the quality of funding decisions. This paper provides a summary of key elements of structural uncertainty describing why it matters and how it could be characterised. Five alternative approaches to characterising structural uncertainty are discussed, including scenario analysis, model selection, model averaging, parameterization and discrepancy. We argue that the potential effect of structural uncertainty on model predictions should be considered in submissions to national funding bodies; however, the characterisation of structural uncertainty is not well defined within the guidelines of these bodies. There has been little consideration of the forms of structural sensitivity analysis that might best inform applied decision-making processes, and empirical research in this area is required.

HS2 - Medication Adherence as a Value Message: A Rarity In Evaluation Assessments Submitted to Major Hta Bodies

Poor or non-adherence causes medical and psychosocial complications for patients and represents a considerable financial burden for health care systems worldwide. Medication adherence problems have not been routinely highly valued by health technology assessment (HTA) bodies in their evaluation assessments. In this study we assess the extent to which leading HTA bodies consider the value of medication adherence in their reimbursement decision making. Evaluation of published assessments made from 2010 to 2013 in five leading HTA bodies (Canadian Agency for Drugs and Technologies in Health (CADTH), the French National Authority for Health (HAS), England’s National Institute of Health and Care Excellence (NICE), the Australian Pharmaceutical Benefits Advisory Committee (PBAC) and the Scottish Medicines Consortium (SMC)) were reviewed for asthma, hypertension, diabetes, multiple sclerosis, psychological disorders and alcohol dependence. The primary outcome measure was to identify the number of assessments in which HTA bodies have considered adherence as a value message. A total of 405 evaluation assessments were submitted to HTA bodies for the above stated indications and timeframe. Out of these assessments, adherence was discussed in 65 (16.1%) of the assessments. However, adherence was not considered valuable for reimbursement decision making by HTA bodies in 19 of these 65 assessments. In the remaining 46 assessments, adherence was considered as a value message while making reimbursement decisions by the HTA bodies but it did not impact the final reimbursement decision in 79% of the instances. Leading HTA bodies have not considered medication adherence as a key metric in their reimbursement decision making.

Relationship between financial impact and coverage of drugs in Australia.

The aim of this study was to estimate the relationship between the financial impact of a new drug and the recommendation for reimbursement by the Australian Pharmaceutical Benefits Advisory Committee (PBAC). Data in the PBAC summary database were abstracted for decisions made between July 2005 and November 2009. Financial impact-the upper bound of the values presented in the PBAC summary database-was categorized as ≤A$0, >A$0 up to A$10 million, A$10 million up to A$30 million, and >A$30 million per year. Descriptive, logistic, survival, and recursive partitioning decision analyses were used to estimate the relationship between the financial impact of a new drug indication and the recommendation for reimbursement. Multivariable analyses controlled for other clinical and economic variables, including cost per quality-adjusted life-year gained. Financial impact was a significant predictor of the recommendation for reimbursement. In the logistic analysis, the odds ratios of reimbursement for drug submissions with financial impacts ≥A$10 million to ≥A$30 million or >A$0 to <A$10 million compared with ≤A$0 were 0.12 (95 percent confidence interval [CI]: 0.03-0.51) and 0.16 (95 percent CI: 0.04-0.60), respectively. In the recursive partition decision analysis, the first split of the data was for submissions with a positive financial impact compared with those with a zero or negative financial impact. In Australia, financial impact on the drug budget is an important determinant of whether a new drug is recommended for reimbursement when cost-effectiveness estimates and other clinical and economic variables are controlled.

Iron chelation therapy in myelodysplastic syndromes: we need more evidence, not more guidelines

Iron chelation therapy in myelodysplastic syndromes: we need more evidence, not more guidelines

Insights from Triangulation of Two Purchase Choice Elicitation Methods to Predict Social Decision Making in Healthcare

Discrete choice experiments (DCEs) and the Juster scale are accepted methods for the prediction of individual purchase probabilities. Nevertheless, these methods have seldom been applied to a social decision-making context. To gain an overview of social decisions for a decision-making population through data triangulation, these two methods were used to understand purchase probability in a social decision-making context. We report an exploratory social decision-making study of pharmaceutical subsidy in Australia. A DCE and selected Juster scale profiles were presented to current and past members of the Australian Pharmaceutical Benefits Advisory Committee and its Economic Subcommittee. Across 66 observations derived from 11 respondents for 6 different pharmaceutical profiles, there was a small overall median difference of 0.024 in the predicted probability of public subsidy (p = 0.003), with the Juster scale predicting the higher likelihood. While consistency was observed at the extremes of the probability scale, the funding probability differed over the mid-range of profiles. There was larger variability in the DCE than Juster predictions within each individual respondent, suggesting the DCE is better able to discriminate between profiles. However, large variation was observed between individuals in the Juster scale but not DCE predictions. It is important to use multiple methods to obtain a complete picture of the probability of purchase or public subsidy in a social decision-making context until further research can elaborate on our findings. This exploratory analysis supports the suggestion that the mixed logit model, which was used for the DCE analysis, may fail to adequately account for preference heterogeneity in some contexts.

PHP116 Clincal and Economic Evidence Bases for Health Technology Assessment: A Comparison of Three Jurisdictions

To understand how different evidence bases may contribute to health technology assessment (HTA) across jurisdictions, we reviewed the evidence considered by three HTA agencies supporting reimbursement recommendations for nine drugs. We selected nine drugs for which the Canadian Common Drug Review (CDR), the Australian Pharmaceutical Benefits Advisory Committee (PBAC), and the National Institute for Health and Clinical Excellence (NICE) had each provided recent reimbursement recommendations. We reviewed the clinical and economic evidence considered for each decision and evaluated whether different evidence bases could have contributed to different HTA decisions. The three HTA agencies agreed (recommended to reimburse) for four drugs and reached different recommendations for five drugs. In both categories, somewhat different evidence bases were used by each agency. For a given drug, different comparators were sometimes considered by different agencies. Even when comparators were common across agencies, there was variability regarding which clinical trials were considered. All agencies considered data from direct, randomized trials, but PBAC and NICE accepted indirect comparisons, whereas CDR did not. Regarding economic outcomes, all NICE decisions made use of cost-effectiveness (mostly cost-utility) analyses, but cost-minimization approaches were considered by CDR and PBAC for several drugs. Overall, NICE provided the most transparent reporting on decision making, and CDR was generally the least transparent of the three. HTA drug decisions across the three countries lack good agreement, and considerable variability exists in the clinical and economic bases considered by CDR, PBAC, and NICE. The reluctance of CDR to accept indirect clinical comparisons, and the propensity of NICE to heed expert advice when analyses were inconclusive may contribute to dissimilar decisions being reached for some drugs. Greater transparency and harmonization of HTA methods have the potential to improve efficiency in health care decision-making, and further research analyzing additional HTA drug decisions is warranted.

The Role of Value for Money in Public Insurance Coverage Decisions for Drugs in Australia: A Retrospective Analysis 1994-2004

To analyze the relative influence of factors in decisions for public insurance coverage of new drugs in Australia. Evidence presented at meetings of the Australian Pharmaceutical Benefits Advisory Committee (PBAC) that makes recommendations on coverage of drugs under Pharmaceutical Benefits Scheme. All major submissions to the PBAC between February 1994 and December 2004 (n = 858) if one of the outcomes measured was life year gained (n=138) or quality-adjusted life years (QALYs) gained (n=116). Clinical significance, cost-effectiveness, cost to government, and severity of disease were significant influences on decisions. Compared to the average submission, clinical significance increased the probability of recommending coverage by 0.21 (95% confidence interval [CI] 0.02 to 0.40), whereas a drug in a life-threatening condition had an increased probability of being recommended for coverage of 0.38 (0.06 to 0.69). An increase in $A10,000 from a mean incremental cost per QALY of $A46,400 reduced the probability of listing by 0.06 (95% CI 0.04 to 0.1). The PBAC provides an example of the long-term stability and coherence of evidence-based coverage and pricing decisions for drugs that weighs up the evidence on clinical effectiveness, clinical need, and value for money. There is no evidence of a fixed public threshold value of life years or QALYs, but willingness to pay is clearly related to the characteristics of the clinical condition, perceived confidence in the evidence of effectiveness and its relevance, as well as total cost to government.