Enabling Equal Access to Molecular Diagnostics: What Are the Implications for Policy and Health Technology Assessment?

Molecular diagnostics can offer important benefits to patients and are a key enabler of the integration of personalised medicine into health care systems. However, despite their promise, few molecular diagnostics are embedded into clinical practice (especially in Europe) and access to these technologies remains unequal across countries and sometimes even within individual countries. If research translation and the regulatory environments have proven to be more challenging than expected, reimbursement and value assessment remain the main barriers to providing patients with equal access to molecular diagnostics. Unclear or non-existent reimbursement pathways, together with the lack of clear evidence requirements, have led to significant delays in the assessment of molecular diagnostics technologies in certain countries. Additionally, the lack of dedicated diagnostics budgets and the siloed nature of resource allocation within certain health care systems have significantly delayed diagnostics commissioning. This article will consider the perspectives of different stakeholders (patients, health care payers, health care professionals, and manufacturers) on the provision of a research-enabled, patient-focused molecular diagnostics platform that supports optimal patient care. Through the discussion of specific case studies, and building on the experience from countries that have successfully integrated molecular diagnostics into clinical practice, this article will discuss the necessary evolutions in policy and health technology assessment to ensure that patients can have equal access to appropriate molecular diagnostics.

Establishing the Evidence Bar for Molecular Diagnostics in Personalised Cancer Care.

While personalised cancer medicine holds great promise, targeting therapies to the biological characteristics of patients is limited by the number of validated biomarkers currently available. The implementation of biomarkers has undergone many challenges with few biomarkers reaching cancer patients in the clinic. There have been many biomarkers that have been published and claimed to be therapeutically useful, but few become part of the clinical decision-making process due to technical, validation and market access issues. To reduce this attrition rate, there is a significant need for policy makers and reimbursement agencies to define specific evidence requirements for the introduction of biomarkers into clinical practice. Once these requirements are more clearly defined, in an analogous manner to pharmaceuticals, researchers and diagnostic companies can better focus their biomarker research and development on meeting these specific requirements, which should lead to the more rapid introduction of new molecular oncology tests for patient benefit.

Cost-effectiveness of the 21-gene breast cancer assay in Mexico.

INTRODUCTION: The 21-gene breast cancer assay (Oncotype DX(®); Genomic Health, Inc.) is a validated diagnostic test that predicts the likelihood of adjuvant chemotherapy benefit and 10-year risk of distant recurrence in patients with hormone-receptor-positive, human epidermal growth receptor 2-negative, early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Mexico. METHODS: A Markov model was developed to make long-term projections of distant recurrence, survival, and direct costs in scenarios using conventional diagnostic procedures or the 21-gene assay to inform adjuvant chemotherapy recommendations. Transition probabilities and risk adjustment were taken from published landmark trials. Costs [2011 Mexican Pesos (MXN)] were estimated from an Instituto Mexicano del Seguro Social perspective. Costs and clinical benefits were discounted at 5% annually. RESULTS: Following assay testing, approximately 66% of patients previously receiving chemotherapy were recommended to receive hormone therapy only after consideration of assay results. Furthermore, approximately 10% of those previously allocated hormone therapy alone had their recommendation changed to add chemotherapy. This optimized therapy allocation led to improved mean life expectancy by 0.068 years per patient and increased direct costs by MXN 1707 [2011 United States Dollars (USD) 129] per patient versus usual care. This is equated to an incremental cost-effectiveness ratio (ICER) of MXN 25,244 (USD 1914) per life-year gained. CONCLUSION: In early-stage breast cancer patients in Mexico, guiding decision making on adjuvant therapy using the 21-gene assay was projected to improve life expectancy in comparison with the current standard of care, with an ICER of MXN 25,244 (USD 1914) per life-year gained, which is within the range generally considered cost-effective.

Cost-effectiveness of biphasic insulin aspart versus insulin glargine in patients with type 2 diabetes in China.

BACKGROUND: The OnceMix and INITIATE studies have indicated that biphasic insulin aspart 30 (BIAsp 30) is more effective than insulin glargine (IGlarg), in terms of glycohemoglobin reductions, in patients with type 2 diabetes initiating insulin therapy. The cost-effectiveness of BIAsp 30 versus IGlarg in the Chinese setting is estimated here. METHODS: The validated and peer-reviewed CORE Diabetes Model was used. The nephropathy, retinopathy, and stroke submodels were modified to incorporate available Chinese clinical data. Diabetes complication costs were derived from hospital surveys in Beijing and Chengdu. Simulated cohorts and insulin treatment effects were based on the OnceMix study for once-daily BIAsp 30 versus IGlarg and on the INITIATE study for twice-daily BIAsp 30 versus IGlarg. Life expectancy and direct medical costs were calculated. Projections were made over 30-year time horizons, with costs and life years discounted at 3% annually. Extensive sensitivity analyses were performed, including adjustments to cardiovascular risk for Chinese ethnicity. RESULTS: Once-daily BIAsp 30 increased life expectancy by 0.04 years (12.37 vs. 12.33 years) and reduced direct medical costs by Chinese Yuan (CNY) 59,710 per patient (CNY 229,911 vs. CNY 289,621 per patient) compared with IGlarg in the OnceMix-based analysis. Twice-daily BIAsp 30 increased life expectancy by 0.08 years (12.99 vs. 12.91 years) and reduced direct medical costs by CNY 107,349 per patient (CNY 303,142 vs. CNY 410,491 per patient) compared with IGlarg in the INITIATE-based analysis. Improvements in life expectancy were driven by reduced incidences of most diabetes-related complications. Cost savings were attributable to lower lifetime insulin costs for BIAsp 30 compared with IGlarg in China. Lowered cardiovascular risk for Chinese ethnicity reduced the projected clinical improvements for BIAsp 30 but increased treatment-related lifetime cost savings. CONCLUSIONS: BIAsp 30, either once- or twice-daily, improved projected life expectancy and reduced projected costs compared with IGlarg in the Chinese setting.

Systematic review of the cost-effectiveness of biphasic insulin aspart 30 in type 2 diabetes.

OBJECTIVES: To review the cost-effectiveness of biphasic insulin aspart (BIAsp 30) compared to other insulin regimens in the treatment of type 2 diabetes based on published literature. METHODS: The electronic databases MEDLINE, EMBASE, the Cochrane Library and EconLit and a selection of congress/meeting databases were systematically searched using combinations of search terms designed to identify publications describing cost-effectiveness analyses of BIAsp 30 in patients with type 2 diabetes. Searches were limited to studies in humans, and published in the English language between January 1999 and July 2009. All records were screened for inclusion in the review. RESULTS: Seven published cost-effectiveness analyses and ten abstracts were identified. One was a health technology assessment from the UK, which evaluated cost-effectiveness using the UKPDS Outcomes Model and meta-analysis of published clinical trials and concluded that premixed insulin analogs were unlikely to be cost-effective versus insulin glargine or biphasic human insulin. In all other studies the cost-effectiveness of BIAsp 30 versus other insulin regimens was assessed using the validated CORE Diabetes Model and outcomes from either the INITIATE randomized controlled trial, or the PRESENT or IMPROVE observational studies. However, notable limitations include the fact that all cost-effectiveness analyses to date have been performed using a single model and that a number of these are based on data from observational studies rather than randomized controlled trials. Nevertheless, long-term clinical and economic outcomes were reported for several countries: UK, US, Sweden, Saudi Arabia, Poland, South Africa, South Korea and China. BIAsp 30 was associated with improvements in quality-adjusted life expectancy in all countries. Estimates of direct costs varied according to country and comparator, but incremental cost-effectiveness ratios for the US and UK were USD 46 533 and GBP 6951 per quality-adjusted life year gained for BIAsp 30 versus insulin glargine. CONCLUSIONS: Although cost-effectiveness data on BIAsp 30 are scarce the majority of the analyses identified in this review suggest that BIAsp 30 is likely to be cost-effective compared to insulin glargine and biphasic human insulin across a wide range of settings, and under certain circumstances would be a dominant treatment option.

The real cost of rabies post-exposure treatments.

The total costs to all payers, i.e., a societal perspective, of four rabies post-exposure regimens were evaluated in two dog bite centres and four local health centres in India. Results showed that the Thai Red Cross intra-dermal regimen (TRC-ID), which uses only one-fifth of the IM dose of purified vero cell vaccine (PVRV) was at most 20% more expensive than use of Purified Chick Embryo Cell (PCEC) vaccine at one-tenth of the IM dose: this cost difference needs to be balanced with the small margin of safety of low potency doses. In local health centres where the staffs are not specially trained in rabies vaccination, the Zagreb intra-muscular regimen is an economical option.