Expected Value of Sample Information to Guide the Design of Group Sequential Clinical Trials

Introduction Adaptive designs allow changes to an ongoing trial based on prespecified early examinations of accrued data. Opportunities are potentially being missed to incorporate health economic considerations into the design of these studies. Methods We describe how to estimate the expected value of sample information for group sequential design adaptive trials. We operationalize this approach in a hypothetical case study using data from a pilot trial. We report the expected value of sample information and expected net benefit of sampling results for 5 design options for the future full-scale trial including the fixed-sample-size design and the group sequential design using either the Pocock stopping rule or the O’Brien-Fleming stopping rule with 2 or 5 analyses. We considered 2 scenarios relating to 1) using the cost-effectiveness model with a traditional approach to the health economic analysis and 2) adjusting the cost-effectiveness analysis to incorporate the bias-adjusted maximum likelihood estimates of trial outcomes to account for the bias that can be generated in adaptive trials. Results The case study demonstrated that the methods developed could be successfully applied in practice. The results showed that the O’Brien-Fleming stopping rule with 2 analyses was the most efficient design with the highest expected net benefit of sampling in the case study. Conclusions Cost-effectiveness considerations are unavoidable in budget-constrained, publicly funded health care systems, and adaptive designs can provide an alternative to costly fixed-sample-size designs. We recommend that when planning a clinical trial, expected value of sample information methods be used to compare possible adaptive and nonadaptive trial designs, with appropriate adjustment, to help justify the choice of design characteristics and ensure the cost-effective use of research funding. Highlights Opportunities are potentially being missed to incorporate health economic considerations into the design of adaptive clinical trials. Existing expected value of sample information analysis methods can be extended to compare possible group sequential and nonadaptive trial designs when planning a clinical trial. We recommend that adjusted analyses be presented to control for the potential impact of the adaptive designs and to maintain the accuracy of the calculations. This approach can help to justify the choice of design characteristics and ensure the cost-effective use of limited research funding.

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Estimating the Expected Value of Sample Information across Different Sample Sizes Using Moment Matching and Nonlinear Regression

Medical Decision Making ◽

10.1177/0272989x19837983 ◽

2019 ◽

Vol 39 (4) ◽

pp. 347-359 ◽

Cited By ~ 2

Author(s):

Anna Heath ◽

Ioanna Manolopoulou ◽

Gianluca Baio

Keyword(s):

Health Economic ◽

Nonlinear Regression ◽

Economic Model ◽

Trial Design ◽

Expected Value ◽

Moment Matching ◽

Sample Sizes ◽

Sample Information ◽

Health Economic Model ◽

The Cost

Background. The expected value of sample information (EVSI) determines the economic value of any future study with a specific design aimed at reducing uncertainty about the parameters underlying a health economic model. This has potential as a tool for trial design; the cost and value of different designs could be compared to find the trial with the greatest net benefit. However, despite recent developments, EVSI analysis can be slow, especially when optimizing over a large number of different designs. Methods. This article develops a method to reduce the computation time required to calculate the EVSI across different sample sizes. Our method extends the moment-matching approach to EVSI estimation to optimize over different sample sizes for the underlying trial while retaining a similar computational cost to a single EVSI estimate. This extension calculates the posterior variance of the net monetary benefit across alternative sample sizes and then uses Bayesian nonlinear regression to estimate the EVSI across these sample sizes. Results. A health economic model developed to assess the cost-effectiveness of interventions for chronic pain demonstrates that this EVSI calculation method is fast and accurate for realistic models. This example also highlights how different trial designs can be compared using the EVSI. Conclusion. The proposed estimation method is fast and accurate when calculating the EVSI across different sample sizes. This will allow researchers to realize the potential of using the EVSI to determine an economically optimal trial design for reducing uncertainty in health economic models. Limitations. Our method involves rerunning the health economic model, which can be more computationally expensive than some recent alternatives, especially in complex models.

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Cost-effectiveness of zoledronic acid compared with sequential denosumab/alendronate for older osteoporotic women in Japan

Archives of Osteoporosis ◽

10.1007/s11657-021-00956-z ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Takahiro Mori ◽

Carolyn J. Crandall ◽

Tomoko Fujii ◽

David A. Ganz

Keyword(s):

Health Economic ◽

Cost Effectiveness ◽

Zoledronic Acid ◽

Cost Saving ◽

Fragility Fracture ◽

Community Dwelling ◽

Sensitivity Analyses ◽

Term Care ◽

Lifetime Horizon ◽

The Cost

Abstract Summary Among hypothetical cohorts of older osteoporotic women without prior fragility fracture in Japan, we evaluated the cost-effectiveness of two treatment strategies using a simulation model. Annual intravenous zoledronic acid for 3 years was cost-saving compared with biannual subcutaneous denosumab for 3 years followed by weekly oral alendronate for 3 years. Purpose Osteoporosis constitutes a major medical and health economic burden to society worldwide. Injectable treatments for osteoporosis require less frequent administration than oral treatments and therefore have higher persistence and adherence with treatment, which could explain better efficacy for fracture prevention. Although annual intravenous zoledronic acid and biannual subcutaneous denosumab are available, it remains unclear which treatment strategy represents a better value from a health economic perspective. Accordingly, we examined the cost-effectiveness of zoledronic acid for 3 years compared with sequential denosumab/alendronate (i.e., denosumab for 3 years followed by oral weekly alendronate for 3 years, making the total treatment duration 6 years) among hypothetical cohorts of community-dwelling osteoporotic women without prior fragility fracture in Japan at ages 65, 70, 75, or 80 years. Methods Using a previously validated and updated Markov microsimulation model, we obtained incremental cost-effectiveness ratios (Japanese yen [¥] (or US dollars [$]) per quality-adjusted life-year [QALY]) from the public healthcare and long-term care payer’s perspective over a lifetime horizon with a willingness-to-pay of ¥5 million (or $47,500) per QALY. Results In the base case, zoledronic acid was cost-saving (i.e., more effective and less expensive) compared with sequential denosumab/alendronate. In deterministic sensitivity analyses, results were sensitive to changes in the efficacy of zoledronic acid or the cumulative persistence rate with zoledronic acid or denosumab. In probabilistic sensitivity analyses, the probabilities of zoledronic acid being cost-effective were 98–100%. Conclusions Among older osteoporotic women without prior fragility fracture in Japan, zoledronic acid was cost-saving compared with sequential denosumab/alendronate.

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P2-284: Introducing a methodology to use activities of daily living outcomes in the assessment of the cost-effectiveness of Alzheimer's disease treatments: A case study using rivastigmine patch

Alzheimer s & Dementia ◽

10.1016/j.jalz.2008.05.1360 ◽

2008 ◽

Vol 4 ◽

pp. T455-T455

Author(s):

Balázs Nagy ◽

Alan Brennan ◽

Agnes Brandtmuller ◽

Simu Thomas ◽

Meghan Gallagher ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cost Effectiveness ◽

Activities Of Daily Living ◽

Daily Living ◽

Rivastigmine Patch ◽

The Cost

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Comparison of Alternative Methods to Assess the Cost-Effectiveness of Tumor-Agnostic Therapies: A Triangulation Approach Using Larotrectinib as a Case Study

Value in Health ◽

10.1016/j.jval.2021.11.1354 ◽

2021 ◽

Author(s):

Andrew Briggs ◽

Beth Wehler ◽

Jennifer G. Gaultney ◽

Alex Upton ◽

Antoine Italiano ◽

...

Keyword(s):

Cost Effectiveness ◽

Alternative Methods ◽

The Cost

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Cost-effectiveness of two long-lasting insecticidal nets delivery models in mass campaign in rural Mozambique

BMC Research Notes ◽

10.1186/s13104-019-4620-6 ◽

2019 ◽

Vol 12 (1) ◽

Author(s):

Jorge A. H. Arroz ◽

Baltazar Candrinho ◽

Chandana Mendis ◽

Melanie Lopez ◽

Maria do Rosário O. Martins

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Universal Coverage ◽

Cost Effectiveness Ratio ◽

Net Benefit ◽

Incremental Net Benefit ◽

The Cost ◽

And Control ◽

Delivery Models ◽

Long Lasting Insecticidal Nets

Abstract Objective The aim is to compare the cost-effectiveness of two long-lasting insecticidal nets (LLINs) delivery models (standard vs. new) in universal coverage (UC) campaigns in rural Mozambique. Results The total financial cost of delivering LLINs was US$ 231,237.30 and US$ 174,790.14 in the intervention (302,648 LLINs were delivered) and control districts (219,613 LLINs were delivered), respectively. The average cost-effectiveness ratio (ACER) per LLIN delivered and ACER per household (HH) achieving UC was lower in the intervention districts. The incremental cost-effectiveness ratio (ICER) per LLIN and ICER per HH reaching UC were US$ 0.68 and US$ 2.24, respectively. Both incremental net benefit (for delivered LLIN and for HHs reaching UC) were positive (intervention deemed cost-effective). Overall, the newer delivery model was the more cost-effective intervention. However, the long-term sustainability of either delivery models is far from guaranteed in Mozambique’s current economic context.

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The effect of precipitation on the Cost-Effectiveness of Sloping land conversion Program: A case study of Shaanxi Province, China

Ecological Indicators ◽

10.1016/j.ecolind.2021.108251 ◽

2021 ◽

Vol 132 ◽

pp. 108251

Author(s):

Shuohua Liu ◽

Shunbo Yao

Keyword(s):

Cost Effectiveness ◽

Shaanxi Province ◽

Land Conversion ◽

Sloping Land Conversion Program ◽

Sloping Land ◽

The Cost

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The Cost-Effectiveness of an Advanced Hybrid Closed-Loop System in People with Type 1 Diabetes: a Health Economic Analysis in Sweden

Diabetes Therapy ◽

10.1007/s13300-021-01157-0 ◽

2021 ◽

Author(s):

Johan Jendle ◽

M. I. Buompensiere ◽

A. L. Holm ◽

S. de Portu ◽

S. J. P. Malkin ◽

...

Keyword(s):

Health Economic ◽

Type 1 Diabetes ◽

Cost Effectiveness ◽

Economic Analysis ◽

Closed Loop ◽

Loop System ◽

Closed Loop System ◽

Health Economic Analysis ◽

The Cost

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The Cost-Effectiveness of an RCT to Establish Whether 5 or 10 Years of Bisphosphonate Treatment Is the Better Duration for Women With a Prior Fracture

Medical Decision Making ◽

10.1177/0272989x09336077 ◽

2009 ◽

Vol 29 (6) ◽

pp. 678-689 ◽

Cited By ~ 12

Author(s):

Matt D. Stevenson ◽

Jeremy E. Oakley ◽

Myfawny Lloyd Jones ◽

Alan Brennan ◽

Juliet E. Compston ◽

...

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Fracture Prevention ◽

Published Data ◽

Bisphosphonate Treatment ◽

Net Benefit ◽

England And Wales ◽

Term Efficacy ◽

The Cost

Purpose. Five years of bisphosphonate treatment have proven efficacy in reducing fractures. Concerns exist that long-term bisphosphonate treatment may actually result in an increased number of fractures. This study evaluates, in the context of England and Wales, whether it is cost-effective to conduct a randomized controlled trial (RCT) and what sample size may be optimal to estimate the efficacy of bisphosphonates in fracture prevention beyond 5 years. Method. An osteoporosis model was constructed to evaluate the cost-effectiveness of extending bisphosphonate treatment from 5 years to 10 years. Two scenarios were run. The 1st uses long-term efficacy data from published literature, and the 2nd uses distributions elicited from clinical experts. Results of a proposed RCT were simulated. The expected value of sample information technique was applied to calculate the expected net benefit of sampling from conducting such an RCT at varying levels of participants per arm and to compare this with proposed trial costs. Results. Without further information, the better duration of bisphosphonate treatment was estimated to be 5 years using the published data but 10 years using the elicited expert opinions, although in both cases uncertainty was substantial. The net benefit of sampling was consistently high when between 2000 and 5000 participants per arm were recruited. Conclusions. An RCT to evaluate the long-term efficacy of bisphosphonates in fracture prevention appears to be cost-effective for informing decision making in England and Wales.

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