Christopher McCabe | University of Alberta (original) (raw)

Papers by Christopher McCabe

PharmacoEconomics, 2012

Previous application of value-of-information methods to optimal clinical trial design have predom... more Previous application of value-of-information methods to optimal clinical trial design have predominantly taken a societal decision-making perspective, implicitly assuming that healthcare costs are covered through public expenditure and trial research is funded by government or donation-based philanthropic agencies. In this paper, we consider the interaction between interrelated perspectives of a societal decision maker (e.g. the National Institute for Health and Clinical Excellence [NICE] in the UK) charged with the responsibility for approving new health interventions for reimbursement and the company that holds the patent for a new intervention. We establish optimal decision making from societal and company perspectives, allowing for trade-offs between the value and cost of research and the price of the new intervention. Given the current level of evidence, there exists a maximum (threshold) price acceptable to the decision maker. Submission for approval with prices above this threshold will be refused. Given the current level of evidence and the decision maker's threshold price, there exists a minimum (threshold) price acceptable to the company. If the decision maker's threshold price exceeds the company's, then current evidence is sufficient since any price between the thresholds is acceptable to both. On the other hand, if the decision maker's threshold price is lower than the company's, then no price is acceptable to both and the company's optimal strategy is to commission additional research. The methods are illustrated using a recent example from the literature.

PharmacoEconomics

Although there have been substantial developments in the analysis of uncertainty in economic eval... more Although there have been substantial developments in the analysis of uncertainty in economic evaluations of health care programmes, the development of methods for one-way sensitivity analysis has been notably slower. Conditional incremental net benefit was recently proposed as an approach for implementing probabilistic one-way sensitivity analysis for economic evaluations comparing two strategies. In this paper, we generalise this approach to economic evaluations that compare three or more strategies. We find that 'conditional net benefit' may be used to conduct probabilistic one-way sensitivity analysis for economic evaluations comparing any number of strategies. We also propose the 'conditional net benefit frontier', which may be used to identify the most cost-effective of any number of strategies conditional upon the specific value of a parameter of interest.

Journal of Clinical Oncology

TPS665 Background: “Multi-parameter” prognostic tests such as Oncotype DX are increasingly used t... more TPS665 Background: “Multi-parameter” prognostic tests such as Oncotype DX are increasingly used to identify women with ER +ve HER2 -ve breast cancer treated with endocrine therapy who are unlikely to benefit meaningfully from adjuvant chemotherapy. The supporting evidence for predictive testing is retrospective and is strongest for women with negative nodes. Randomised trials to validate testing are in progress but more evidence is needed, especially for node positive disease. There is early evidence that other multi-parameter tests which are in development have a predictive utility. Methods: OPTIMA will assess the value of multi-parameter tests in a UK population. OPTIMA prelim, the feasibility phase, will recruit 300 patients from May 2012 (with a 200 patient bridging extension to the main study). Eligible patients will have ER +ve HER2 -ve tumours with involved nodes (pN1-2). Patients will be randomised to the standard arm of both chemotherapy and endocrine therapy, or to the “te...

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Sep 1, 2018

Next-generation sequencing (NGS) is considered to be a prominent example of "big data" ... more Next-generation sequencing (NGS) is considered to be a prominent example of "big data" because of the quantity and complexity of data it produces and because it presents an opportunity to use powerful information sources that could reduce clinical and health economic uncertainty at a patient level. One obstacle to translating NGS into routine health care has been a lack of clinical trials evaluating NGS technologies, which could be used to populate cost-effectiveness analyses (CEAs). A key question is whether big data can be used to partially support CEAs of NGS. This question has been brought into sharp focus with the creation of large national sequencing initiatives. In this article we summarize the main methodological and practical challenges of using big data as an input into CEAs of NGS. Our focus is on the challenges of using large observational datasets and cohort studies and linking these data to the genomic information obtained from NGS, as is being pursued in the...

Health technology assessment (Winchester, England), 2018

Rheumatoid arthritis (RA), the most common autoimmune disease in the UK, is a chronic systemic in... more Rheumatoid arthritis (RA), the most common autoimmune disease in the UK, is a chronic systemic inflammatory arthritis that affects 0.8% of the UK population. To determine whether or not an alternative class of biologic disease-modifying antirheumatic drugs (bDMARDs) are comparable to rituximab in terms of efficacy and safety outcomes in patients with RA in whom initial tumour necrosis factor inhibitor (TNFi) bDMARD and methotrexate (MTX) therapy failed because of inefficacy. Multicentre, Phase III, open-label, parallel-group, three-arm, non-inferiority randomised controlled trial comparing the clinical and cost-effectiveness of alternative TNFi and abatacept with that of rituximab (and background MTX therapy). Eligible consenting patients were randomised in a 1 : 1 : 1 ratio using minimisation incorporating a random element. Minimisation factors were centre, disease duration, non-response category and seropositive/seronegative status. UK outpatient rheumatology departments. Patients...

Nature reviews. Clinical oncology, 2018

Pharmaceutical statistics, Jan 20, 2018

It is well documented that the modelling of health-related quality of life data is difficult as t... more It is well documented that the modelling of health-related quality of life data is difficult as the distribution of such data is often strongly right/left skewed and it includes a significant percentage of observations at one. The objective of this study is to develop a series of two-part models (TPMs) that deal with these issues. Data from the UK Medical Research Council Myeloma IX trial were used to examine the relationship between the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/QLQ-MY20 scores and the European QoL-5 Dimensions (EQ-5D) utility score. Four different TPMs were developed. The models fitted included TPM with normal regression, TPM with normal regression with variance a function of participant characteristics, TPM with log-transformed data, and TPM with gamma regression and a log link. The cohort of 1839 patients was divided into 75% derivation sample, to fit the different models, and 25% validation sample to assess the predictive ability...

Canadian Urological Association journal = Journal de l'Association des urologues du Canada, Jan 22, 2017

BMC endocrine disorders, Jan 30, 2018

Although current beta cell replacement therapy is effective in stabilizing glycemic control in hi... more Although current beta cell replacement therapy is effective in stabilizing glycemic control in highly selected patients with refractory type 1 diabetes, many hurdles are inherent to this and other donor-based transplantation methods. One solution could be moving to stem cell-derived transplant tissue. This study investigates a novel stem cell-derived graft and implant technology and explores the circumstances of its cost-effectiveness compared to intensive insulin therapy. We used a manufacturing optimization model based on work by Simaria et al. to model cost of the stem cell-based transplant doses and integrated its results into a cost-effectiveness model of diabetes treatments. The disease model simulated marginal differences in clinical effects and costs between the new technology and our comparator intensive insulin therapy. The form of beta cell replacement therapy was as a series of retrievable subcutaneous implant devices which protect the enclosed pancreatic progenitors cel...

Health technology assessment (Winchester, England), Nov 1, 2017

Treat to target (TTT) is a broad concept for treating patients with rheumatoid arthritis (RA). It... more Treat to target (TTT) is a broad concept for treating patients with rheumatoid arthritis (RA). It involves setting a treatment target, usually remission or low disease activity (LDA). This is often combined with frequent patient assessment and intensive and rapidly adjusted drug treatment, sometimes based on a formal protocol. To investigate the clinical effectiveness and cost-effectiveness of TTT compared with routine care. Databases including EMBASE and MEDLINE were searched from 2008 to August 2016. A systematic review of clinical effectiveness was conducted. Studies were grouped according to comparisons made: (1) TTT compared with usual care, (2) different targets and (3) different treatment protocols. Trials were subgrouped by early or established disease populations. Study heterogeneity precluded meta-analyses. Narrative synthesis was undertaken for the first two comparisons, but was not feasible for the third. A systematic review of cost-effectiveness was also undertaken. No ...

Journal of Obstetrics and Gynaecology Canada

Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. ... more Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. Different screening strategies select approximately 4% of women for invasive fetal chromosome testing. Non-invasive prenatal testing (NIPT) using maternal blood cell-free DNA could reduce those invasive procedures but is expensive. This study evaluated the cost-effectiveness of NIPT strategies compared with conventional strategies. This study used a decision analytic model to estimate the cost-effectiveness of 13 prenatal screening strategies for fetal aneuploidies: six frequently used strategies, universal NIPT, and six strategies incorporating NIPT as a second-tier test. The study considered a virtual cohort of pregnant women of similar size and age as women in Quebec. Model data were obtained from published sources and government databases. The study predicted the number of chromosomal anomalies detected (trisomies 21, 13, and 18), invasive procedures and euploid fetal losses, direct costs, and incremental cost-effectiveness ratios. Of the 13 strategies compared, eight identified fewer cases at a higher cost than at least one of the remaining five strategies. Integrated serum screening with conditional NIPT had the lowest cost, and the cost per case detected was 63139,witha9063 139, with a 90% reduction of invasive procedures. The number of cases identified was improved with four other screening strategies, but with increasing of incremental costs per case (from 63139,witha9061 623 to $1 553 615). Results remained robust, except when NIPT costs and risk cut-offs varied. NIPT as a second-tier test for high-risk women is likely to be cost-effective as compared with screening algorithms not involving NIPT.

Frontiers in psychiatry, 2017

Here, we report on findings from a 15-month follow-up of a school-based program called Empowering... more Here, we report on findings from a 15-month follow-up of a school-based program called Empowering a Multimodal Pathway Toward Healthy Youth (EMPATHY). This was primarily intended to reduce suicidal thinking in pre-teens, adolescents, and youth students aged 11-18 in middle schools (Grades 6-8) and high SCHOOLS (Grades 9-12). It also aimed to reduce depression and anxiety. The EMPATHY multimodal program consisted of repeated data collection, identification of a high-risk group, a rapid intervention for this high-risk group including offering supervised online cognitive behavioral therapy (CBT) program, a universal CBT intervention for those in Grades 6-8, a variety of interactions with trained staff ("Resiliency Coaches"), and referral to external medical and psychiatric services where appropriate. There were four time-points at which assessments were made: baseline, 3, 7, and 15 months. Here, we report cross-sectional findings over 15 months in a total of 6,227 students wh...

PharmacoEconomics, Jan 9, 2017

The volume and technical complexity of both academic and commercial research using decision analy... more The volume and technical complexity of both academic and commercial research using decision analytic modelling has increased rapidly over the last two decades. The range of software programs used for their implementation has also increased, but it remains true that a small number of programs account for the vast majority of cost-effectiveness modelling work. We report a comparison of four software programs: TreeAge Pro, Microsoft Excel, R and MATLAB. Our focus is on software commonly used for building Markov models and decision trees to conduct cohort simulations, given their predominance in the published literature around cost-effectiveness modelling. Our comparison uses three qualitative criteria as proposed by Eddy et al.: "transparency and validation", "learning curve" and "capability". In addition, we introduce the quantitative criterion of processing speed. We also consider the cost of each program to academic users and commercial users. We rank t...

Nature, 2017

The field of quantum computing will soon achieve a historic milestone -quantum supremacy. It is s... more The field of quantum computing will soon achieve a historic milestone -quantum supremacy. It is still unknown whether application-related algorithms will be able to deliver big increases in speed using the sorts of processors that will soon be available. But when quantum hardware becomes sufficiently powerful, it will become possible to test this and develop new types of algorithms.

PharmacoEconomics, 2016

Twenty years ago, the "Panel on Cost-effectivene... more Twenty years ago, the "Panel on Cost-effectiveness in Health and Medicine" published a landmark text setting out appropriate methods for conducting cost-effectiveness analyses of health technologies. In the two decades since, the methods used for economic evaluations have advanced substantially. Recently, a "second panel" (hereafter "the panel") was convened to update the text and its recommendations were published in November 2016. The purpose of this paper is to critique the panel's updated guidance regarding the discounting of costs and health effects. The advances in discounting methodology since the first panel include greater theoretical clarity regarding the specification of discount rates, how these rates vary with the analytical perspective chosen, and whether the healthcare budget is constrained. More specifically, there has been an important resolution of the debate regarding the conditions under which differential discounting of costs and health effects is appropriate. We show that the panel's recommendations are inconsistent with this recent literature. Importantly, the panel's departures from previously published findings do not arise from an alternative interpretation of theory; rather, we demonstrate that this is due to fundamental errors in methodology and logic. The panel also failed to conduct a formal review of relevant empirical evidence. We provide a number of suggestions for how the panel's recommendations could be improved in future.

Medical decision making : an international journal of the Society for Medical Decision Making, Jan 23, 2016

The cost-effectiveness threshold in health care systems with a constrained budget should be deter... more The cost-effectiveness threshold in health care systems with a constrained budget should be determined by the cost-effectiveness of displacing health care services to fund new interventions. Using comparative statics, we review some potential determinants of the threshold, including the budget for health care, the demand for existing health care interventions, the technical efficiency of existing interventions, and the development of new health technologies. We consider the anticipated direction of impact that would affect the threshold following a change in each of these determinants. Where the health care system is technically efficient, an increase in the health care budget unambiguously raises the threshold, whereas an increase in the demand for existing, non-marginal health interventions unambiguously lowers the threshold. Improvements in the technical efficiency of existing interventions may raise or lower the threshold, depending on the cause of the improvement in efficiency,...

Cell stem cell, Jan 7, 2016

PharmacoEconomics, 2012

Previous application of value-of-information methods to optimal clinical trial design have predom... more Previous application of value-of-information methods to optimal clinical trial design have predominantly taken a societal decision-making perspective, implicitly assuming that healthcare costs are covered through public expenditure and trial research is funded by government or donation-based philanthropic agencies. In this paper, we consider the interaction between interrelated perspectives of a societal decision maker (e.g. the National Institute for Health and Clinical Excellence [NICE] in the UK) charged with the responsibility for approving new health interventions for reimbursement and the company that holds the patent for a new intervention. We establish optimal decision making from societal and company perspectives, allowing for trade-offs between the value and cost of research and the price of the new intervention. Given the current level of evidence, there exists a maximum (threshold) price acceptable to the decision maker. Submission for approval with prices above this threshold will be refused. Given the current level of evidence and the decision maker's threshold price, there exists a minimum (threshold) price acceptable to the company. If the decision maker's threshold price exceeds the company's, then current evidence is sufficient since any price between the thresholds is acceptable to both. On the other hand, if the decision maker's threshold price is lower than the company's, then no price is acceptable to both and the company's optimal strategy is to commission additional research. The methods are illustrated using a recent example from the literature.

PharmacoEconomics

Although there have been substantial developments in the analysis of uncertainty in economic eval... more Although there have been substantial developments in the analysis of uncertainty in economic evaluations of health care programmes, the development of methods for one-way sensitivity analysis has been notably slower. Conditional incremental net benefit was recently proposed as an approach for implementing probabilistic one-way sensitivity analysis for economic evaluations comparing two strategies. In this paper, we generalise this approach to economic evaluations that compare three or more strategies. We find that 'conditional net benefit' may be used to conduct probabilistic one-way sensitivity analysis for economic evaluations comparing any number of strategies. We also propose the 'conditional net benefit frontier', which may be used to identify the most cost-effective of any number of strategies conditional upon the specific value of a parameter of interest.

Journal of Clinical Oncology

TPS665 Background: “Multi-parameter” prognostic tests such as Oncotype DX are increasingly used t... more TPS665 Background: “Multi-parameter” prognostic tests such as Oncotype DX are increasingly used to identify women with ER +ve HER2 -ve breast cancer treated with endocrine therapy who are unlikely to benefit meaningfully from adjuvant chemotherapy. The supporting evidence for predictive testing is retrospective and is strongest for women with negative nodes. Randomised trials to validate testing are in progress but more evidence is needed, especially for node positive disease. There is early evidence that other multi-parameter tests which are in development have a predictive utility. Methods: OPTIMA will assess the value of multi-parameter tests in a UK population. OPTIMA prelim, the feasibility phase, will recruit 300 patients from May 2012 (with a 200 patient bridging extension to the main study). Eligible patients will have ER +ve HER2 -ve tumours with involved nodes (pN1-2). Patients will be randomised to the standard arm of both chemotherapy and endocrine therapy, or to the “te...

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Sep 1, 2018

Next-generation sequencing (NGS) is considered to be a prominent example of "big data" ... more Next-generation sequencing (NGS) is considered to be a prominent example of "big data" because of the quantity and complexity of data it produces and because it presents an opportunity to use powerful information sources that could reduce clinical and health economic uncertainty at a patient level. One obstacle to translating NGS into routine health care has been a lack of clinical trials evaluating NGS technologies, which could be used to populate cost-effectiveness analyses (CEAs). A key question is whether big data can be used to partially support CEAs of NGS. This question has been brought into sharp focus with the creation of large national sequencing initiatives. In this article we summarize the main methodological and practical challenges of using big data as an input into CEAs of NGS. Our focus is on the challenges of using large observational datasets and cohort studies and linking these data to the genomic information obtained from NGS, as is being pursued in the...

Health technology assessment (Winchester, England), 2018

Rheumatoid arthritis (RA), the most common autoimmune disease in the UK, is a chronic systemic in... more Rheumatoid arthritis (RA), the most common autoimmune disease in the UK, is a chronic systemic inflammatory arthritis that affects 0.8% of the UK population. To determine whether or not an alternative class of biologic disease-modifying antirheumatic drugs (bDMARDs) are comparable to rituximab in terms of efficacy and safety outcomes in patients with RA in whom initial tumour necrosis factor inhibitor (TNFi) bDMARD and methotrexate (MTX) therapy failed because of inefficacy. Multicentre, Phase III, open-label, parallel-group, three-arm, non-inferiority randomised controlled trial comparing the clinical and cost-effectiveness of alternative TNFi and abatacept with that of rituximab (and background MTX therapy). Eligible consenting patients were randomised in a 1 : 1 : 1 ratio using minimisation incorporating a random element. Minimisation factors were centre, disease duration, non-response category and seropositive/seronegative status. UK outpatient rheumatology departments. Patients...

Nature reviews. Clinical oncology, 2018

Pharmaceutical statistics, Jan 20, 2018

It is well documented that the modelling of health-related quality of life data is difficult as t... more It is well documented that the modelling of health-related quality of life data is difficult as the distribution of such data is often strongly right/left skewed and it includes a significant percentage of observations at one. The objective of this study is to develop a series of two-part models (TPMs) that deal with these issues. Data from the UK Medical Research Council Myeloma IX trial were used to examine the relationship between the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/QLQ-MY20 scores and the European QoL-5 Dimensions (EQ-5D) utility score. Four different TPMs were developed. The models fitted included TPM with normal regression, TPM with normal regression with variance a function of participant characteristics, TPM with log-transformed data, and TPM with gamma regression and a log link. The cohort of 1839 patients was divided into 75% derivation sample, to fit the different models, and 25% validation sample to assess the predictive ability...

Canadian Urological Association journal = Journal de l'Association des urologues du Canada, Jan 22, 2017

BMC endocrine disorders, Jan 30, 2018

Although current beta cell replacement therapy is effective in stabilizing glycemic control in hi... more Although current beta cell replacement therapy is effective in stabilizing glycemic control in highly selected patients with refractory type 1 diabetes, many hurdles are inherent to this and other donor-based transplantation methods. One solution could be moving to stem cell-derived transplant tissue. This study investigates a novel stem cell-derived graft and implant technology and explores the circumstances of its cost-effectiveness compared to intensive insulin therapy. We used a manufacturing optimization model based on work by Simaria et al. to model cost of the stem cell-based transplant doses and integrated its results into a cost-effectiveness model of diabetes treatments. The disease model simulated marginal differences in clinical effects and costs between the new technology and our comparator intensive insulin therapy. The form of beta cell replacement therapy was as a series of retrievable subcutaneous implant devices which protect the enclosed pancreatic progenitors cel...

Health technology assessment (Winchester, England), Nov 1, 2017

Treat to target (TTT) is a broad concept for treating patients with rheumatoid arthritis (RA). It... more Treat to target (TTT) is a broad concept for treating patients with rheumatoid arthritis (RA). It involves setting a treatment target, usually remission or low disease activity (LDA). This is often combined with frequent patient assessment and intensive and rapidly adjusted drug treatment, sometimes based on a formal protocol. To investigate the clinical effectiveness and cost-effectiveness of TTT compared with routine care. Databases including EMBASE and MEDLINE were searched from 2008 to August 2016. A systematic review of clinical effectiveness was conducted. Studies were grouped according to comparisons made: (1) TTT compared with usual care, (2) different targets and (3) different treatment protocols. Trials were subgrouped by early or established disease populations. Study heterogeneity precluded meta-analyses. Narrative synthesis was undertaken for the first two comparisons, but was not feasible for the third. A systematic review of cost-effectiveness was also undertaken. No ...

Journal of Obstetrics and Gynaecology Canada

Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. ... more Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. Different screening strategies select approximately 4% of women for invasive fetal chromosome testing. Non-invasive prenatal testing (NIPT) using maternal blood cell-free DNA could reduce those invasive procedures but is expensive. This study evaluated the cost-effectiveness of NIPT strategies compared with conventional strategies. This study used a decision analytic model to estimate the cost-effectiveness of 13 prenatal screening strategies for fetal aneuploidies: six frequently used strategies, universal NIPT, and six strategies incorporating NIPT as a second-tier test. The study considered a virtual cohort of pregnant women of similar size and age as women in Quebec. Model data were obtained from published sources and government databases. The study predicted the number of chromosomal anomalies detected (trisomies 21, 13, and 18), invasive procedures and euploid fetal losses, direct costs, and incremental cost-effectiveness ratios. Of the 13 strategies compared, eight identified fewer cases at a higher cost than at least one of the remaining five strategies. Integrated serum screening with conditional NIPT had the lowest cost, and the cost per case detected was 63139,witha9063 139, with a 90% reduction of invasive procedures. The number of cases identified was improved with four other screening strategies, but with increasing of incremental costs per case (from 63139,witha9061 623 to $1 553 615). Results remained robust, except when NIPT costs and risk cut-offs varied. NIPT as a second-tier test for high-risk women is likely to be cost-effective as compared with screening algorithms not involving NIPT.

Frontiers in psychiatry, 2017

Here, we report on findings from a 15-month follow-up of a school-based program called Empowering... more Here, we report on findings from a 15-month follow-up of a school-based program called Empowering a Multimodal Pathway Toward Healthy Youth (EMPATHY). This was primarily intended to reduce suicidal thinking in pre-teens, adolescents, and youth students aged 11-18 in middle schools (Grades 6-8) and high SCHOOLS (Grades 9-12). It also aimed to reduce depression and anxiety. The EMPATHY multimodal program consisted of repeated data collection, identification of a high-risk group, a rapid intervention for this high-risk group including offering supervised online cognitive behavioral therapy (CBT) program, a universal CBT intervention for those in Grades 6-8, a variety of interactions with trained staff ("Resiliency Coaches"), and referral to external medical and psychiatric services where appropriate. There were four time-points at which assessments were made: baseline, 3, 7, and 15 months. Here, we report cross-sectional findings over 15 months in a total of 6,227 students wh...

PharmacoEconomics, Jan 9, 2017

The volume and technical complexity of both academic and commercial research using decision analy... more The volume and technical complexity of both academic and commercial research using decision analytic modelling has increased rapidly over the last two decades. The range of software programs used for their implementation has also increased, but it remains true that a small number of programs account for the vast majority of cost-effectiveness modelling work. We report a comparison of four software programs: TreeAge Pro, Microsoft Excel, R and MATLAB. Our focus is on software commonly used for building Markov models and decision trees to conduct cohort simulations, given their predominance in the published literature around cost-effectiveness modelling. Our comparison uses three qualitative criteria as proposed by Eddy et al.: "transparency and validation", "learning curve" and "capability". In addition, we introduce the quantitative criterion of processing speed. We also consider the cost of each program to academic users and commercial users. We rank t...

Nature, 2017

The field of quantum computing will soon achieve a historic milestone -quantum supremacy. It is s... more The field of quantum computing will soon achieve a historic milestone -quantum supremacy. It is still unknown whether application-related algorithms will be able to deliver big increases in speed using the sorts of processors that will soon be available. But when quantum hardware becomes sufficiently powerful, it will become possible to test this and develop new types of algorithms.

PharmacoEconomics, 2016

Twenty years ago, the "Panel on Cost-effectivene... more Twenty years ago, the "Panel on Cost-effectiveness in Health and Medicine" published a landmark text setting out appropriate methods for conducting cost-effectiveness analyses of health technologies. In the two decades since, the methods used for economic evaluations have advanced substantially. Recently, a "second panel" (hereafter "the panel") was convened to update the text and its recommendations were published in November 2016. The purpose of this paper is to critique the panel's updated guidance regarding the discounting of costs and health effects. The advances in discounting methodology since the first panel include greater theoretical clarity regarding the specification of discount rates, how these rates vary with the analytical perspective chosen, and whether the healthcare budget is constrained. More specifically, there has been an important resolution of the debate regarding the conditions under which differential discounting of costs and health effects is appropriate. We show that the panel's recommendations are inconsistent with this recent literature. Importantly, the panel's departures from previously published findings do not arise from an alternative interpretation of theory; rather, we demonstrate that this is due to fundamental errors in methodology and logic. The panel also failed to conduct a formal review of relevant empirical evidence. We provide a number of suggestions for how the panel's recommendations could be improved in future.

Medical decision making : an international journal of the Society for Medical Decision Making, Jan 23, 2016

The cost-effectiveness threshold in health care systems with a constrained budget should be deter... more The cost-effectiveness threshold in health care systems with a constrained budget should be determined by the cost-effectiveness of displacing health care services to fund new interventions. Using comparative statics, we review some potential determinants of the threshold, including the budget for health care, the demand for existing health care interventions, the technical efficiency of existing interventions, and the development of new health technologies. We consider the anticipated direction of impact that would affect the threshold following a change in each of these determinants. Where the health care system is technically efficient, an increase in the health care budget unambiguously raises the threshold, whereas an increase in the demand for existing, non-marginal health interventions unambiguously lowers the threshold. Improvements in the technical efficiency of existing interventions may raise or lower the threshold, depending on the cause of the improvement in efficiency,...

Cell stem cell, Jan 7, 2016

Background: Islet cell transplantation is a method to stabilize type 1 diabetes patients with hyp... more Background: Islet cell transplantation is a method to stabilize type 1 diabetes patients with hypoglycemia unawareness and unstable blood glucose levels by reducing insulin dependency and protecting against severe hypoglycemia through restoring endogenous insulin secretion. This study analyses the current cost-effectiveness of this technology and estimates the value of further research to reduce uncertainty around cost-effectiveness. Methods: We performed a cost-utility analysis using a Markov cohort model with a mean patient age of 49 to simulate costs and health outcomes over a lifetime horizon. Our analysis used intensive insulin therapy (IIT) as comparator and took the provincial healthcare provider perspective. Cost and effectiveness data for up to four transplantations per patient came from the University of Alberta hospital. Costs are expressed in 2012 Canadian dollars and effectiveness in quality-adjusted life-years (QALYs) and life years. To characterize the uncertainty around expected outcomes, we carried out a probabilistic sensitivity analysis within the Bayesian decision-analytic framework. We performed a value-of-information analysis to identify priority areas for future research under various scenarios. We applied a structural sensitivity analysis to assess the dependence of outcomes on model characteristics. Results: Compared to IIT, islet cell transplantation using non-generic (generic) immunosuppression had additional costs of 150,006(150,006 (150,006(112,023) per additional QALY, an average gain of 3.3 life years, and a probability of being cost-effective of 0.5 % (28.3 %) at a willingness-to-pay threshold of 100,000perQALY.Atthisthresholdthenon−generictechnologyhasanexpectedvalueofperfectinformation(EVPI)of100,000 per QALY. At this threshold the non-generic technology has an expected value of perfect information (EVPI) of 100,000perQALY.Atthisthresholdthenon−generictechnologyhasanexpectedvalueofperfectinformation(EVPI)of260,744 for Alberta. This increases substantially in cost-reduction scenarios. The research areas with the highest partial EVPI are costs, followed by natural history, and effectiveness and safety. Conclusions: Current transplantation technology provides substantial improvements in health outcomes over conventional therapy for highly selected patients with 'unstable' type 1 diabetes. However, it is much more costly and so is not cost-effective. The value of further research into the cost-effectiveness is dependent upon treatment costs. Further, we suggest the value of information should not only be derived from current data alone when knowing that this data will most likely change in the future.