Multi-actor system dynamics in access to disease-modifying treatments for multiple sclerosis in Southeast Asia: A regional survey and suggestions for improvement.

BACKGROUND: Despite the global availability of multiple sclerosis (MS) treatments, accessing and financing them in Southeast Asia (SEA) remains a challenge. This descriptive survey-based study aimed to describe the current state of MS treatment access and local access dynamics within this region. METHODS: The survey questionnaire, comprising of 15 closed-ended and five open-ended questions, was developed by three neurologists with expertise in MS and routine MS patient management, or had training in neuroimmunology. Questionnaire development was guided by the recent Atlas of MS and in alignment with the Access to Treatment framework, focusing on MS diagnosis and treatment issues in SEA. Fifteen neurologists experienced in managing MS across the region were identified as key informants for this study. RESULTS: All fifteen neurologists participated in the survey via email and videoconferencing between January 2020 and February 2023, which included the following countries: Brunei, Cambodia, Indonesia, Malaysia, Myanmar, Lao PDR, Philippines, Singapore, Thailand, Timor-Leste, and Vietnam. All had at least five years of experience in managing MS patients and six had previously completed a neuroimmunology fellowship programme. SEA countries showed disparities in healthcare financing, availability of neurologists, MS treatments, and investigative tools. Access to MS disease-modifying treatments (DMTs) is hindered by high cost, lack of MS specialists, and weak advocacy efforts. On-label DMTs are not listed as essential medicines regionally except for interferon beta1a and teriflunomide in Malaysia. On-label monoclonals are available only in Malaysia, Singapore, and Thailand. Generic on-label DMTs are unavailable due to lack of distributorship and expertise in using them. Off-label DMTs (azathioprine, methotrexate, and rituximab) predominate in most SEA countries. Other challenges include limited access to investigations, education, and knowledge about DMTs among general neurologists, and absence of registries and MS societies. Patient champions, communities, and MS organisations have limited influence on local governments and pharmaceutical companies. Despite its increasing prevalence, there is a lack of concerted priority setting due to MS being perceived as a rare, non-communicable disease. CONCLUSION: This study highlights the distinct dynamics, challenges, and research gaps within this region, and provides suggestions to improve MS diagnosis, education, and medicine access.

Availability, affordability, and quality of essential anti-seizure medication in Cambodia.

OBJECTIVE: Epilepsy is a major neurological disorder that requires long-term medical treatment. Once epilepsy is diagnosed, people with epilepsy face many difficulties in accessing treatment (treatment gap). Our objective was to assess the situation regarding the availability, price, affordability, and quality of anti-seizure medication (ASM), which are major determinants of access to treatment. METHOD: A cross-sectional study was performed in provincial/district hospitals and private pharmacies in urban and rural areas in Cambodia. Data on ASM availability and price were obtained through drug suppliers. Affordability was estimated as the number of day wages the lowest-paid government employee must work to purchase a monthly treatment. Samples of ASM were collected, and the quality of ASM was assessed through Medicine Quality Assessment Reporting Guidelines. RESULTS: Out of 138 outlets visited, only 72 outlets (52.2% [95% CI 43.5-60.7]) had at least one ASM available. Phenobarbital 100 mg was the most available (35.5%), followed by carbamazepine 200 mg (21.7%), phenobarbital 50 mg (11.6%), sodium valproate 500 mg (9.4%), and phenytoin 100 mg (9.4%). In provincial/district hospitals, ASM was provided free of charge. In private pharmacies, affordability for phenobarbital 50 mg and 100 mg was the best, with 0.6 and 0.5 days, respectively, compared to phenytoin 100 mg (1.8 days), and other ASM. No counterfeit ASM was found in this study. Phenytoin sample presented the worst quality (33.0%) compared to carbamazepine (27.8%), and other ASM. SIGNIFICANCE: A lack of access to affordable and effective ASM due to low availability and poor quality of ASM was identified. Our research highlights the need for future policy efforts to ensure the quality of ASM and improve their availability. This can be achieved by involving the calculation of their annual needs for these drugs and increasing the national production of ASM.

Community-based management of epilepsy in Southeast Asia: Two intervention strategies in Lao PDR and Cambodia.

BACKGROUND: Epilepsy affects more than 50 million people worldwide, 80% of whom live in low- and middle-income countries (LMICs). In Southeast Asia, the prevalence is moderate (6‰), and the main public health challenge is reducing the treatment gap, which reaches more than 90% in rural areas. METHODS: This 12-month comparative study (intervention vs. control areas) assessed the community effectiveness of two different strategies for the identification and home follow-up of people with epilepsy by Domestic Health Visitors for epilepsy (DHVes). In Lao PDR, DHVes were health center staff covering several villages via monthly visits; in Cambodia, DHVes were health volunteers living in the villages. FINDINGS: At baseline, the treatment gap was >95% in Lao PDR and 100% in Cambodia. After 12 months, the treatment gap in Lao PDR decreased by 5·5% (range: 4·0-12·2) in the intervention area and 0·5% (range: 0·4-0·8) in the control area (p<0·0001). In Cambodia, the treatment gap decreased by 34·9% (range: 29·0-44·1) in the intervention area and 8·1% (range: 6·7-10·2) in the control area (p<0·0001). Among the PWEs followed at home by the DHVes, the proportion adhering to drug treatment was 85·2% in Lao PDR and 78·1% in Cambodia. The cost associated with strategy implemented in Cambodia, compared with the control area, was lower than the cost associated with strategy implemented in Lao PDR." INTERPRETATION: The treatment gap was significantly reduced with both intervention strategies, but the effect was larger in Cambodia. The results of this cost analysis pave the way for scaling-up in rural areas of Lao PDR and Cambodia, and experimental adaptation in other LMICs. FUNDING: The study was funded by the Global Health Department of Sanofi and Grand Challenges Canada (grant number 0325-04).

Differences in knowledge about epilepsy and antiepileptic drugs among pharmacy-dispensing workers in Cambodia and in Lao PDR.

Epilepsy is the most common neurological disorder encountered in primary care in Southeast Asia. People with epilepsy require long-term therapy management. Nonadherence to antiepileptic drugs (AEDs) has been identified as a major factor in suboptimal control of epilepsy. Pharmacies offer patients a first-line point of contact with the healthcare system. Many pharmacies operate with limited or nonqualified human resources that can lead to insufficient knowledge, inappropriate supply of medicines, and insufficient counseling. OBJECTIVE: The aim of this study was to evaluate the qualification and knowledge concerning epilepsy and AEDs among pharmacy-dispensing workers who sell drugs to people with epilepsy. METHOD: A cross-sectional qualitative study was conducted in public and private pharmacies, in both urban and rural areas of Cambodia and Lao People's Democratic Republic (Lao PDR). The knowledge was collected through a questionnaire. RESULTS: A total of 180 respondents from 123 outlets in the two countries were included in this study. A proportion of 40.8% (31) of respondents in Cambodia and 38.5% (40) in Lao PDR were pharmacists, followed by sellers who did not received any healthcare training with a proportion of 18.4% (14) in Cambodia compared to 20.2% (21) in Lao PDR. Head trauma was cited as the main cause of epilepsy by 72.4% (55) in Cambodia and 27.2% (28) in Lao PDR (p < 0.001). Epilepsy was considered as a contagious disease by 6.6% (5) of respondents in Cambodia compared to 18.4% (19) in Lao PDR (p = 0.03). Eighty-seven percent (66) of respondents in Cambodia knew at least one long-term AED versus 67.3% (70) in Lao PDR (p = 0.003). Phenobarbital was mentioned in more than 90.0% of cases in both countries. In overall, 15.4% (21) thought that if seizures are controlled for some months, people with epilepsy could stop taking their AEDs. Only one respondent from Lao PDR was aware of drug-drug interaction between AEDs and oral contraception. CONCLUSION: An educational intervention should be implemented to improve the knowledge of epilepsy and AEDs for pharmacy-dispensing workers. This could include advice for all pharmacy-dispensing workers in order to improve AED management and follow-up of therapeutic adherence.

Epilepsy: some controversies, some knowledge and some experience from Cambodia.

Epilepsy-related health outcomes remain unacceptably low in much of the developing world. According to us, it is because of the failure since long to see, and address, epilepsy beyond its preset conventional image. The objective of this paper was to highlight the presence, and influence, of these conventional practices and also to demonstrate what happened when a bold unconventional approach to address epilepsy was taken in Cambodia. Data are taken from existing published literature on epilepsy as well as our field experience during several population-based surveys conducted in Cambodia. We complimented this with our knowledge gained over this long period. It is demonstrated that epilepsy is far more important in Asia that it is currently considered to be, and also vis-à-vis other geographic regions. Pregnancy and birth-related factors carry far higher odds for epilepsy than several "highly vocal" infections. A refocus in epilepsy is required to help move from its traditional negative image to an image where epilepsy is considered a "positive-looking" disorder that is full of "opportunities;" such as availability of safe effective inexpensive treatment, etc. Stigma is a two-side entity (i.e., it is present, and it is influential), and diligence should be therefore practiced before using the stigma label. Nevertheless, psychosocial aspects shouldn't be limited to stigma or Jacoby stigma scale alone. Quality of life is a subjective phenomenon, and patients should determine directly what affects them. It is highly desirable that if we want to find newer answers to old problems in epilepsy, we need to shed our conventional approach and preset conclusions. We should choose to move toward "opportunities" visibly present in epilepsy. Our Cambodian experience demonstrates more intimately that opportunities do get identified when preset conclusions are questioned, and an approach that goes beyond expected and by default is taken.