Impact of a Forced Dose-Equivalent Levothyroxine Brand Switch on Plasma Thyrotropin: A Cohort Study.

Background: Patients with primary hypothyroidism are treated with levothyroxine (LT4) to normalize their serum thyrotropin (TSH). Finding the optimal dosage is a long-lasting process, and a small change can have major impact. Currently, limited data are available on the impact of dose-equivalent substitution between brands. This study aimed to determine the effect of the shortage of the LT4 brand Thyrax® in the Netherlands and the resulting dose-equivalent switch to another brand on plasma TSH concentrations in a large cohort of patients. Methods: Observational cohort study. Two registries representative for the Dutch population containing prescription and laboratory test data: the Nivel Primary Care Database and the PHARMO Database Network. Patients using at least 25 µg Thyrax daily for one year or longer were included. Two cohorts were formed: a switch cohort consisting of patients who switched from Thyrax to an alternative brand, and a Thyrax cohort including patients who continued to use Thyrax. Patients in the switch cohort did switch from Thyrax to a different brand of LT4 in 2016 and had two consecutive TSH measurements on the same dose of LT4, one before and one 6 weeks after the switch. Patients in the Thyrax cohort had two consecutive TSH measurements on the same dose of Thyrax that were 6 weeks apart. Results: In the Thyrax cohort, 19% of euthyroid patients using ≤100 µg had a TSH level outside the reference range at the subsequent measurement compared with 24% in the switch cohort (p < 0.0001). For patients using >100 µg Thyrax, these figures were 24% and 63%, respectively (p < 0.0001). Furthermore, patients using >50 µg Thyrax were four to five times more likely to become hyperthyroid after a dose-equivalent switch to a different brand compared with patients who stayed on Thyrax. Conclusions: In euthyroid patients continuing the LT4 product Thyrax at the same dose, TSH was out of range in 19-24% at least 6 weeks later. A dose-equivalent switch from Thyrax to other LT4 brands induced biochemical signs of overdosing in an even larger proportion (24-63%) of patients. The results indicate that a dose-equivalent LT4 brand switch may necessitate a dose adjustment in a large number of patients.

Priority setting for health research: toward a management process for low and middle income countries (Working Paper 1)

This Working Paper documents the interactions of a ‘think tank’ consultation, initiated by COHRED, bringing together health research managers from Brazil, South Africa, The Netherlands, The Philippines, the private sector, the Pan American Health Organization (PAHO), the Global Forum for Health Research and COHRED. Its purpose was to better understand the issues countries face and their needs in moving priority setting forward as well as seeking advice from professionals on how COHRED can support them in managing a process of setting and measuring progress in health research priorities. Rather than having priorities ‘reviewed’ and ‘set’ through a workshop or national activity that produces a plan reflecting the situation at one point in time, the discussion in this think tank examined what process is needed so that national health research priorities are managed in a dynamic way, and are measured, updated and can evolve with the reality of the national, operational and political context. (...)