The WHO health systems Building Blocks framework has become ubiquitous in health systems research. However, it was not developed as a research instrument, but rather to facilitate investments of resources in health systems. In this paper, we reflect on the advantages and limitations of using the framework in applied research, as experienced in three empirical vaccine studies we have undertaken.

Objectives To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia. Design Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study). Setting Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda. Participants 522 480 children and adults with acute febrile illness. Interventions Rapid diagnostic tests for malaria. Main outcome measures Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings. Results Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole. Conclusions Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials—a beneficial public health outcome—could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription.This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined.

To synthesise lessons learnt and determinants of success from human papillomavirus (HPV) vaccine demonstration projects and national programmes in low- and middle-income countries (LAMICs). Interviews were conducted with 56 key informants. A systematic literature review identified 2936 abstracts from five databases; after screening 61 full texts were included. Unpublished literature, including evaluation reports, was solicited from country representatives; 188 documents were received. A data extraction tool and interview topic guide outlining key areas of inquiry were informed by World Health Organization guidelines for new vaccine introduction. Results were synthesised thematically. Data were analysed from 12 national programmes and 66 demonstration projects in 46 countries. Among demonstration projects, 30 were supported by the GARDASIL^® Access Program, 20 by Gavi, four by PATH and 12 by other means. School-based vaccine delivery supplemented with health facility-based delivery for out-of-school girls attained high coverage. There were limited data on facility-only strategies and little evaluation of strategies to reach out-of-school girls. Early engagement of teachers as partners in social mobilisation, consent, vaccination day coordination, follow-up of non-completers and adverse events was considered invaluable. Micro-planning using school/ facility registers most effectively enumerated target populations; other estimates proved inaccurate, leading to vaccine under- or over-estimation. Refresher training on adverse events and safe injection procedures was usually necessary. Considerable experience in HPV vaccine delivery in LAMICs is available. Lessons are generally consistent across countries and dissemination of these could improve HPV vaccine introduction.

Objective: To review published frameworks that included criteria for the assessment of external validity, applicability and transferability in their assessment of health research. Methods: Five databases were searched for articles relating to the assessment of external validity or applicability and transferability in health research. A coding framework was developed inductively and used to assess which types of criteria were included in the frameworks. Results: Thirty-eight articles describing 25 frameworks were identified. Eleven focused solely on the assessment of applicability and transferability; 14 presented more general decision-making or evidence appraisal frameworks. The criteria were synthesized into four main categories: setting, intervention, outcomes and evidence. None of the frameworks covered all the criteria identified. A major limitation was the lack of empirical data used to develop many frameworks and the apparent lack of assessment of their perceived utility. Conclusion: A validated framework of applicability and transferability would help those aiming to encourage research use, as well as those conducting research. Greater understanding of applicability and transferability could help to encourage the appropriate use of research and the development of research that is more useful.

Since 2007, HPV vaccine has been available to low and middle income countries (LAMIC) for small-scale 'demonstration projects', or national programmes. We analysed coverage achieved in HPV vaccine demonstration projects and national programmes that had completed at least 6 months of implementation between January 2007-2016. A mapping exercise identified 45 LAMICs with HPV vaccine delivery experience. Estimates of coverage and factors influencing coverage were obtained from 56 key informant interviews, a systematic published literature search of 5 databases that identified 61 relevant full texts and 188 solicited unpublished documents, including coverage surveys. Coverage achievements were analysed descriptively against country or project/programme characteristics. Heterogeneity in data, funder requirements, and project/programme design precluded multivariate analysis. Estimates of uptake, schedule completion rates and/or final dose coverage were available from 41 of 45 LAMICs included in the study. Only 17 estimates from 13 countries were from coverage surveys, most were administrative data. Final dose coverage estimates were all over 50% with most between 70% and 90%, and showed no trend over time. The majority of delivery strategies included schools as a vaccination venue. In countries with school enrolment rates below 90%, inclusion of strategies to reach out-of-school girls contributed to obtaining high coverage compared to school-only strategies. There was no correlation between final dose coverage and estimated recurrent financial costs of delivery from cost analyses. Coverage achieved during joint delivery of HPV vaccine combined with another intervention was variable with little/no evaluation of the correlates of success. This is the most comprehensive descriptive analysis of HPV vaccine coverage in LAMICs to date. It is possible to deliver HPV vaccine with excellent coverage in LAMICs. Further good quality data are needed from health facility based delivery strategies and national programmes to aid policymakers to effectively and sustainably scale-up HPV vaccination.

Social mobilisation during new vaccine introductions encourages acceptance, uptake and adherence to multi-dose schedules. Effective communication is considered especially important for human papillomavirus (HPV) vaccine, which targets girls of an often-novel age group. This study synthesised experiences and lessons learnt around social mobilisation, consent, and acceptability during 55 HPV vaccine demonstration projects and 8 national programmes in 37 low and middle-income countries (LMICs) between January 2007 and January 2015. A qualitative study design included: (i) a systematic review, in which 1,301 abstracts from five databases were screened and 41 publications included; (ii) soliciting 124 unpublished documents from governments and partner institutions; and (iii) conducting 27 key informant interviews. Data were extracted and analysed thematically. Additionally, first-dose coverage rates were categorised as above 90 %, 90–70 %, and below 70 %, and cross-tabulated with mobilisation timing, message content, materials and methods of delivery, and consent procedures. All but one delivery experience achieved over 70 % first-dose coverage; 60 % achieved over 90 %. Key informants emphasized the benefits of starting social mobilisation early and actively addressing rumours as they emerged. Interactive communication with parents appeared to achieve higher first-dose coverage than non-interactive messaging. Written parental consent (i.e., opt-in), though frequently used, resulted in lower reported coverage than implied consent (i.e., opt-out). Protection against cervical cancer was the primary reason for vaccine acceptability, whereas fear of adverse effects, exposure to rumours, lack of project/programme awareness, and schoolgirl absenteeism were major reasons for non-vaccination. Despite some challenges in obtaining parental consent and addressing rumours, experiences indicated effective social mobilisation and high HPV vaccine acceptability in LMICs. Social mobilisation, consent, and acceptability lessons were consistent across world regions and HPV vaccination projects/programmes. These can be used to guide HPV vaccination communication strategies without additional formative research.