Implementation of Single-Pill Combination Medication for Hypertension Treatment by Nonphysician Health Care Workers at Primary Healthcare Facilities in Nigeria: An Explanatory Mixed Methods Study

Study design

This explanatory sequential mixed methods study drew on quantitative data from a cluster RCT embedded within the HTN Program (27). Details of the HTN Program have been previously published (20, 21). Briefly, 60 PHCs from six area councils (local governments) in the Federal Capital Territory of Nigeria were selected for the HTN Program, which conducted an embedded cluster RCT (1:1, n = 60 clusters) from January 2021 to June 2021 to evaluate the effectiveness and implementation of a two-drug SPC at Steps 2 and 3 provided to patients, compared with providing separate pills, on the odds of hypertension control at six months (19). SPC antihypertensive therapy was implemented in 30 of the 60 participating PHCs. Nonphysician HCWs, including CHEWs and nurses, received structured training on a simplified, protocol-based hypertension treatment algorithm covering screening, diagnosis, patient education, and SPC use at Steps 2 and 3. Interactive sessions included demonstrations and role-playing. During the trial, SPC medications were provided at no cost; a Drug Revolving Fund (DRF) scheme subsidized costs afterward. Eligible patients identified through facility-based screening were enrolled, initiated on SPC therapy, and followed up monthly for BP monitoring, medication refills, and documentation. To maintain fidelity to the treatment protocol, nonphysician HCWs received ongoing on-site mentorship and quarterly supportive supervision from the research team (19).

Quantitative data on RE-AIM outcomes were used to inform the subsequent qualitative data collection, which was conducted between September and December 2021 using focus group discussions (FGDs) and key informant interviews (KIIs). The Consolidated criteria for Reporting Qualitative research (COREQ) checklist guided the reporting of qualitative methods and findings (Supplement 1) (29). The results of the embedded cluster RCT have been published (19) while relevant program reports were reported as proportions.

Quantitative study

Qualitative study

Mixed method data integration

Mixed methods analysis was performed to assess factors that facilitated or hindered the implementation and effectiveness of SPC. Guided by RE-AIM QuEST, qualitative data explained quantitative findings from the embedded trial and identified contextual factors influencing reach, adoption, fidelity, and maintenance. Additionally, findings from the quantitative data informed the development of the semi-structured guides.

Quantitative results

There was wide reach, as all 30 PHCs assigned to provide SPC therapy for BP treatment implemented the intervention. Effectiveness was demonstrated by a mean BP rate of 54% (95% CI: 0.52, 0.56) among 2,381 patients at six months in the SPC arm and 48% (95% CI: 0.46, 0.50) among 2,046 in the free-equivalent arm (unadjusted risk difference = 6.0 pp; 95% CI: 2% to 10%, cluster adjusted p value = 0.29). Adoption was high, with all facilities dispensing SPC at least once during the study period. At least one nonphysician HCW in each PHC was trained to prescribe SPC in line with Steps 2 and 3 of the treatment protocol. Implementation fidelity improved progressively over the six-month trial, with the proportion of enrolled hypertensive patients who were dispensed an SPC at intervention sites increasing from 21% in Month 1 to 37% in Month 6. Maintenance at the patient level was moderate, with 49% of patients in the SPC arm remaining in care at six months. At baseline, none of the participating PHCs were dispensing SPCs; by six months, all SPC facilities were actively prescribing and dispensing the medication, a measure of facility-level maintenance, consistent with the protocol-defined indicators for maintenance of the intervention. At the facility-level, maintenance was also demonstrated by sustained treatment delivery above baseline values, with average facility-level BP control increasing from 14% at baseline to 54% at six months (19, 21).

Qualitative results

Reach

Effectiveness

Adoption

Implementation (Fidelity)

Maintenance

Reach and adoption

HCWs’ acceptability of SPCs for the treatment of hypertension was demonstrated by high levels of reach and adoption in this study. This universal adoption also reflects the feasibility of integrating the use of SPCs into PHCs in similar low-resource settings (10, 11, 31). The perceived benefits of SPCs and the role of training in facilitating HCWs’ adoption of the use of SPC are similar to the findings by Mbuthia et al. in Kenya, which highlighted the role of capacity-building for HCWs in prescribing SPC and providing medication adherence counseling for patients (32). The free provision of medications in both the SPC and comparator groups reduced financial barriers, enabling access even in rural areas where hypertension services have historically been limited (4). Increased attendance may therefore reflect the effect of the zero-cost medication rather than the SPC modality alone. Hence, the feasibility of the task-sharing strategy to improve access to treatment with SPC is complemented by the mitigation of financial barriers for patients. These findings are consistent with findings from similar settings in Africa where task-sharing/shifting initiatives improved access, but cost and geographic barriers remain critical determinants of access to care (32, 33).

Effectiveness

The embedded cluster RCT within the HTN Program found that SPCs were as effective as free-equivalent antihypertensive medications for achieving BP control when prescribed by nonphysician HCWs at Steps 2 and 3 of the treatment protocol (19). This result contrasts with findings from the VERONICA trial in Nigeria and the TRIUMPH trial in Sri Lanka, where initiating therapy with SPCs demonstrated superior effectiveness compared with free-equivalent regimens, with BP control rates of 82% versus 72% and 70% versus 55%, respectively (10, 11). This difference may reflect the timing of SPC introduction: in the HTN Program, SPCs were introduced at later treatment steps, whereas VERONICA and TRIUMPH evaluated first-line SPC initiation (10, 11). Together, these findings underscore that while SPCs may not always show superior clinical effectiveness when introduced later in the treatment protocol, they offer meaningful implementation advantages, including simplified prescribing and enhanced adherence, which warrant evaluation in real-world primary healthcare settings (6, 10, 11, 19).

Despite this, the 54% BP control rate observed among patients randomized to receive SPCs in the HTN Program represents a notable achievement in the Nigerian context, where national hypertension control rates are estimated at 12%, and global control rates average less than 30% (1, 34). In some African countries, rates are reported as low as 7%, highlighting the substantial gap in effective hypertension management across the continent (34, 35).

These findings align with evidence from other LMICs demonstrating that task-sharing models combined with simplified treatment protocols can achieve substantial improvements in hypertension control (6, 32). High-quality studies have also shown that SPC regimens enhance adherence by reducing pill burden, thereby improving clinical outcomes and facilitating hypertension management in resource-limited settings (33, 34).

Implementation (Fidelity)

The relatively high BP control rate observed in this study suggests that adherence to treatment protocols by HCWs for patients on SPCs likely contributed to their effectiveness. However, the proportions of eligible patients placed on SPCs over the six months (21–37%) highlight gaps in fidelity to consistent SPC prescribing. Despite high levels of reach and adoption, not all eligible patients received SPCs as expected. This suggests that, while SPCs contributed to BP control in over half of the treated patients, broader application could have further improved hypertension outcomes (36, 37). Several factors potentially influenced HCWs’ fidelity, including concerns about side effects, patient monitoring practices, availability of medications, and supportive supervision. Although dispensing increased over time, qualitative findings indicate that supply-chain interruptions, intermittent stockouts, and patient-level factors may have limited consistent SPC use, though HCWs did not perceive these factors as significant barriers. These findings align with previous literature on implementation barriers to antihypertensive medication uptake and fidelity (32, 38, 39, 40, 41). Higher SPC use among patients in the SPC arm of the RCT near the study end attenuates this concern, which may suggest growing HCW familiarity, improved supply, or adaptation over time.

Reservations from some policymakers and HCWs regarding the ability to identify specific drug components responsible for side effects are consistent with previous research, including from Kenya (32, 42). These concerns underscore the importance of equipping HCWs with the skills to monitor and manage adverse effects (43). The HTN Program’s structured training on SPC prescribing may have mitigated some of these knowledge gaps (32). There were also mixed opinions on the scope of nonphysician HCWs’ roles in hypertension management. While many stakeholders expressed optimism about their involvement, some advocated restricting their responsibilities to early-stage hypertension and simple two-drug SPCs. These perceptions align with findings by Adeyemo et al. on the perception of physicians on the management of hypertension by nonphysician HCWs in Nigeria (44). Challenges related to side effect management and the limited availability of diverse SPC formulations to address patient variability have also been reported in other LMIC settings (6, 32). The role of supportive supervision emerged as a key strategy to strengthen fidelity and ensure adherence to SPC protocols. Similar task-sharing/shifting initiatives in resource-limited settings have successfully leveraged regular supervision to maintain quality of care (43, 45, 46). Supportive supervision was a core element of the HTN Program’s implementation strategy and likely contributed to its success, including the effective use of SPCs (19, 47).

Maintenance

While SPCs offer clear advantages for hypertension management, sustaining their use in resource-limited PHCs staffed by nonphysician HCWs presents notable challenges. These challenges include limited availability, supply chain disruptions, high cost, and insufficient awareness among healthcare providers, as noted by Salam et al. (6). These implementation barriers are consistent with our findings where stockouts and potential high out-of-pocket costs have been reported, especially with purchases from private pharmacies. Although SPCs are often perceived as more expensive than free-equivalent regimens (48, 49), evidence suggests that large-scale procurement through governments or insurance schemes can offset costs and render SPCs cost-effective (6, 50). These findings related to the affordability of BP-lowering medications, including SPC, are consistent with prior research (51, 52, 53). The planned introduction of a DRF scheme to mitigate stockouts and sustain supply at a subsidized cost aligns with global and local recommendations and practices (54). Results on the implementation and effectiveness of the use of a DRF scheme in the HTN Program indicate that a DRF can mitigate the challenges associated with stockouts of quality BP-lowering medications and lower subsequent out-of-pocket costs for patients (62). The reported stockouts of SPCs may have been linked to the global supply chain disruption during the COVID-19 pandemic in 2020–2021 (55, 56, 57). Furthermore, the HTN Program’s efforts to sustain SPC supply could leverage community-based insurance initiatives, such as the Basic Health Care Provision Fund, which directly finances PHCs in Nigeria and provides a platform for scaling up SPC therapies (52, 58, 59).

Strengths and limitations

This study complements several studies that have demonstrated the acceptability and advantages of SPCs from the patient’s perspective (50). The study adds to this evidence by providing insights into the nonphysician HCWs’ perspectives on using SPC for the treatment of hypertension. While the sample size was small and thus the results may not be generalizable beyond the Federal Capital Territory of Nigeria, they provide contextual inferences on implementation that could guide in similar contexts, especially with similar primary healthcare structures throughout and beyond Nigeria. This study may have benefited from a comparative qualitative inquiry on the perspective of nonphysician HCW in using the free-equivalent medication; however, baseline assessment of the HTN Program suggested the nonphysician HCWs were more familiar with the use of the free-equivalent medications for treatment of hypertension (24). Although the focus of this study was on the perspective of HCWs, it may have benefited from additional insights from patients. While social desirability bias is a potential concern in qualitative research, its impact may have been mitigated by the perspectives of key informants, including policymakers and regulators. As all medications were provided free of charge during the study, Reach may have been enhanced by the availability of free drugs rather than by the SPC intervention alone. This has important implications for sustainability and scalability, which were partially addressed through the establishment of a DRF at HTN Program sites after the trial concluded, which is designed to provide hypertension medications at low cost.