Questions/Answers

The objective of this initiative is to provide universal access to an innovation of severe cutaneous adverse drug reactions (SCARs) prevention. Since SCARs, such as Steven-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), are preventable health problems in an excellent quality health care system (Lozano, 2018), prevention of SCARs is the best strategy to improve the quality of the health care system. One of the innovative tools to prevent SCARs is a risk assessment by examining the patients’ genetic information before prescribing the medicine. These genetic tests related to the prescription of medicine are called “Pharmacogenetics”. The HLA-B*15:02 gene is a strong risk factor for the carbamazepine (anti-epileptic drug)-induced SCARs. The test for this gene is usually expensive and requires sophisticated equipment. The cost occurring from the test cannot be reimbursed in Thailand health system. These factors limit the implementation of pharmacogenetics to prevent SCARs in the public health settings. Department of Medical Sciences (DMSc) and collaborative partners handled the development of low-cost genetic tests, health economic evaluation, and policy introduction to establish the country-wide pharmacogenetics tests under the universal coverage scheme, covering 48 million Thai people. The incidence of SCARs reduced dramatically after the successful establishment of these innovative interventions.

criteria Category 1 1 This initiative introduces the low-cost genetic tests, and universal health coverage to prevent adverse drug reactions, according to SDG 3.8. 2 The genetic tests are cost effective and available nationwide. 3 The universal health coverage enables the access for all people including the vulnerable. 4 The universities and Epilepsy Society of Thailand actively participate and contribute to accelerate this initiative. 5 Facebook page was set up for distributing the information about this initiative. 6 The services are provided according to the international clinical service standard, ISO15189. DMSc also has the complaint system for improving the service.

The initiative complies with SDG3 by enabling everyone, including the vulnerable at all ages, to benefit from this drug with a close to zero risk of suffering from SJS/TEN. In addition, this laboratory-developed method was petty patented and further developed into a test kit assisting coverage across Thailand and South East Asia region. The implementation of this potential method was announced by National Health Security Office. Thailand is the third country which the government announces a policy of genetic risk testing for Thai-people. Furthermore, the technology transfer led to sustainable development for healthy life and well-being for all.

After an introduction of pharmacogenetics for prevention of SCARs, the total number of SCARs reported in Thailand was reduced from 975 cases in 2013 to 729 cases in 2016 (25.2% reduction). Incidences of Carbamazepine-induced SCARs are 100-150 cases per year. With universal health coverage, the Carbamazepine-induced SCARs reduced from 131 cases to 42 cases (78% reduction) in 2016. This incidence is expected to reduce to less than 10 cases (90% reduction) after the introduction of the genetic test into the benefit package of universal health coverage scheme. The perception of adverse drug reactions in health care providers has been changing from the unpredictable and unavoidable to the preventable issue. This perception generates a paradigm shift among health care providers in Thailand.

The initiative is unprecedented and has never been developed before in Thailand. The novelty of this innovation is supported by granting of petty patent no. 8735 titled with “HLA-B*15:02 allele genetic testing process” issued by Department of Intellectual Development, Ministry of Commerce. Additionally, the test is convenient and intuitive because it is compatible with basic laboratory infrastructures in public medical laboratory and do not require complicated expensive equipment and software. The test also has higher sensitivity and specificity compared to commercial kits. The test kit based on this laboratory-developed method received “social innovation award” by National Innovation Agency in 2015.

Thailand is the first upper-middle income country that adopted this genetic test in the universal coverage scheme. The processes of implementation include the health economics study (Rattanavipapong, 2013) and the development of clinical practice guidelines for epilepsy (The epilepsy society of Thailand, 2016). Based on these attempts, the National Health Security Office, announced in 28th June, 2018 that this test is covered by the universal coverage scheme.

The concept of this initiative has been distributed in the research network within the Southeast Asia region (www.seapharm.org). The genetic test was evaluated in Indonesia (Yuliwulundari, et al., 2017) and Philippines (Capule, et al., 2018), and the health economics evaluation in Malaysia was performed (Chong et al., 2017). This evidence proves transferability of this concept other countries in Southeast Asia. The initiative was likewise mentioned as the best practices in the international community implementing the genetic test for public health.

A resource for implementation the HLA-B*15:02 genetic risk testing is cost effective based on the health economic evaluation published report (Rattanavipapong et al., 2013). The cost of the genetic testing is offset by the reduced cost from the treatment providing to the patients developed adverse drug reactions and the higher proportion of patients that can access to the drug with lower rates of adverse drug reactions.

For social aspects, continuous knowledge transfer raised awareness for stakeholders. More hospitals are requesting for HLA-B*15:02 genetic risk testing each year. The test also included in universal health coverage by National Health Security Office. For economic aspects, prevention of SJS/TEN continuously reduce cost for acute and long-term treatment and development of the testing was petty patented to ensure sustainability for Thailand economy. In addition, the laboratory-developed test is 20-time cheaper than a commercial kit. For environment aspects, the test requires less consumables and more environment friendly when compared to other methods to the simplicity and affordability of the design.

Yes

The HLA-B*15:02 genetic risk testing was evaluated through external evaluation by Health Intervention and Technology Assessment Program (HITAP) in 2014. The establishment of laboratory network by DMSc and guideline from Epilepsy Society of Thailand led to inclusion of the test in to national healthcare system in 2018. The test was also awarded from many organizations such as National Innovation Agency (NIA), Office of The Public Sector Development Commission (OPDC).

The indicator for evaluation of HLA-B*15:02 genetic risk testing is 88% reduction of Carbamazepine-induced SJS/TEN after implementation of the HLA-B*15:02 genetic risk testing service prior to Carbamazepine administration. The Health Technology Assessment result has been referred to National Health Security Office.

The outcome of evaluation was shown by announcement of inclusion of the testing as privilege in National Health Insurance System ensuring that all patients at all ages including the vulnerable can benefit from Carbamazepine without SJS/TEN.

There are three groups of stakeholders; the government agencies in the Ministry of Public Health, the medical schools and the professional societies, engaged in establishment of the universal access to this genetic test in Thailand. The clinical researches were done to confirm that HLA-B*15:02 is genetic risk for Carbamazepine-induced SJS/TEN. All researchers, including experts from Food and Drug Administration and clinical experts from The Queen Sirikrit National Center for Child Health in Department of Medical Services were invited into the brainstorming session. DMSc established the low-cost genetic test development and preparation of the national laboratory network. Under collaborating with Bangkok branch of NHSO along with three Faculty of Medicine (Chulalongkorn University, Ramathibodi Hospital, and Siriraj Hospital), DMSc conducted the pilot genetic test service program in Bangkok. DMSc also worked with HITAP for the health economics evaluation, and with the Epilepsy Society for updating the guideline to include the HLA-B*15:02 recommendation. The test is also suitable for business industry since the process of HLA-B*15:02 genetic risk testing has been petty-patented and is ready for technology and knowledge transfer. All in all stakeholders including children, women and the vulnerable would benefit from Carbamazepine with minimum risk of SJS/TEN.

Establishing universal access for the genetic test is a very long term process. Without the collaboration among the local and national health authorities in Thailand, Thai people would not be able to benefit from this innovation. The success of inclusion of the testing to the universal health coverage required 9 years process, from the idea conception to the announcement. This process is the most important lesson learned from this initiative and Thailand is establishing the workflow across government agencies for fastening this process for the next innovation, for the benefit of Thai people.