Pilot approach to analyzing patient and citizen involvement in health technology assessment in four diverse low- and middle-income countries.

BACKGROUND: In low- and middle-income countries (LMICs) striving to achieve universal health coverage, the involvement of different stakeholders in formal or informal ways in health technology assessment (HTA) must be culturally and socially relevant and acceptable. Challenges may be different from those seen in high-income countries. In this article, we aimed to pilot a questionnaire for uncovering the context-related aspects of patient and citizen involvement (PCI) in LMICs, collecting experiences encountered with PCI, and identifying opportunities for patients and citizens toward contributing to local decision- and policy-making processes related to health technologies. METHODS: Through a collaborative, international multi-stakeholder initiative, a questionnaire was developed for describing each LMIC's healthcare system context and the emergence of opportunities for PCI relating to HTA. The questionnaire was piloted in the first set of countries (Brazil, Indonesia, Nigeria, and South Africa). RESULTS: The questionnaire was successfully applied across four diverse LMICs, which are at different stages of using HTA to inform decision making. Only in Brazil, formal ways of PCI have been defined. In the other countries, there is informal influence that is contingent upon the engagement level of patient and citizen advocacy groups (PCAGs), usually strongest in areas such as HIV/AIDS, TB, oncology, or rare diseases. CONCLUSIONS: The questionnaire can be used to analyze the options for patients and citizens to participate in HTA or healthcare decision making. It will be rolled out to more LMICs to describe the requirements and opportunities for PCI in the context of LMICs and to identify possible routes and methodologies for devising a more systematic and formalized PCI in LMICs.

M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds.

Germline mutations in codon 918 of exon 16 of the RET gene (M918T) are classically associated with multiple endocrine neoplasia type 2B (MEN 2B) with highly aggressive medullary thyroid cancer (MTC), pheochromocytoma and a unique phenotype. The objectives of this study are to describe the rare M918V RET mutation discovered in 8 MTC kindreds from Brazil lacking the MEN 2B phenotype classically observed in M918T patients and to investigate the presence of a founder effect for this germline mutation. Eight apparently sporadic MTC cases were diagnosed with the germline M918V RET mutation. Subsequently, their relatives underwent clinical and genetic assessment (n = 113), and M918V was found in 42 of them. Until today, 20/50 M918V carriers underwent thyroidectomy and all presented MTC/C-cell hyperplasia; the remainder carriers are on clinical follow-up. None of the M918V carriers presented clinical features of MEN 2B. Their clinical presentation was heterogeneous, and the age at tumor diagnosis ranged from 24 to 59 years. Lymph node metastases were present in 12/20 patients, and presumable distant metastases in 2/20; in contrast, we observed a carrier of up to 87 years of age without evidence of MTC. Ethnographic fieldwork and haplotype analyses suggested that the founder mutation first settled in that area fifteen generations ago and originated from Portugal. Our study is the first to demonstrate the RET M918V mutation co-segregating in 8 familial MTC kindreds with validated evidence of a founder effect. We suggest that M918V MTC should be clinically considered an American Thyroid Association (ATA) moderate-risk category.