Controlled temperature chain for vaccination in low- and middle-income countries: a realist evidence synthesis.

Objective: To evaluate the evidence describing how the controlled temperature chain approach for vaccination could lead to improved equitable immunization coverage in low- and middle-income countries. Methods: We created a theory of change construct from the Findings: We evaluated 34 articles, describing 22 unique controlled temperature chain or closely related experiences across four World Health Organization regions. We identified a strong demand for this approach among service delivery providers; however, generating an equal level of demand among policy-makers requires greater evidence on economic benefits and on vaccination coverage gains, and use case definitions. Consistent evidence supported safety of the approach when integrated into special vaccination programmes. Feasible training and supervision supported providers in complying with protocols. Time-savings were the main evidence for efficiency gains, while cost-saving data were minimal. Improved equitable coverage was reported where vaccine storage beyond the cold chain enabled access to hard-to-reach populations. No evidence indicated an inferior vaccine effectiveness nor increased adverse event rates for vaccines delivered under the approach. Conclusion: Synthesized evidence broadly supported the initial theory of change. Addressing evidence gaps on economic benefits and coverage gains may increase future uptake.