Efficiency and quality in conducting clinical trials in sub-Saharan Africa

Background
The conduct of clinical trials is significantly regulated and requires substantial infrastructure and human resource investments and efforts. Clinical research centers in sub-Saharan Africa face particular constraints by the increasing trial related workload and administration, paired with capacity limitations. At the same time, trials are critically important for improving public health in these settings. We investigated the challenges in clinical trial conduct to optimize the efficiency of processes in sub- Saharan Africa while maintaining quality. Our working hypothesis was that the Good Clinical Practice guideline, is not adapted to these particular situations, and that its possibly overly strict interpretation was the main challenge.
Methods
We used an exploratory mixed methods design: First, we performed key informant interviews asking questions about quality, guidelines, challenges, and inefficiencies in clinical trials. We interviewed 60 clinical trial staff of different professional levels in two clinical research centers in Kenya, Ghana, Burkina Faso, and Senegal. The study covered English- and French-speaking, and Eastern and Western parts of sub-Saharan Africa. Content analysis was performed to identify themes across settings and positions, respectively. Emerging themes from data interrogation were tested in further interview analysis. We used MAXQDA software for the analysis. Second, we developed an online survey investigating trial protocol suitability based on the main interview themes. We distributed the survey by email to trial staff based in sub-Saharan Africa. We used the statistical software STATA for the analysis of categorical variables and to perform explorative factor analysis.
Results
We found various internal factors associated with constraining trial efficiency in sub-Saharan Africa. Internal factors are limited to those that exclusively relate to clinical trial teams and sponsors. These factors may be influenced independently of external conditions and may significantly increase trial efficiency if addressed by the respective teams. Identified internal factors were summarized in the two broad themes “planning” and “site organisation”. “Planning” factors related to budget feasibility, clear project ideas, realistic deadlines, understanding of trial processes, adaptation to the local context, and involvement of site staff in planning. “Site organisation” factors covered staff turnover, employment conditions, career paths, workload, delegation and management.
Protocol suitability surfaced as another prominent internal topic in interviews with trial staff. By following the topic up in an online survey we found that the main constraints of protocol suitability were a lack of clarity, implementability, and adaptation to trial participants as well as to available workforce and infrastructure. In both, qualitative and quantitative investigations local site staff involvement in protocol development was identified as the most helpful measure to increase protocol suitability.
Unexpectedly, the administrative burden resulting from the guidelines was not perceived as a difficulty; rather, researchers were grateful for having guidance by a globally accepted standard. Only in regards to informed consent did some clinical trial staff (one-third) perceive the guideline as insufficiently applicable.
Conclusions
Our data suggest that adequate and coherent planning, clear task allocation and strengthening of management capacity may help to overcome the identified internal factors and allow clinical trials to proceed more efficiently. In addition a careful assessment of the setting with a particular focus on available workforce and infrastructure as well as the needs and availability of trial participants was perceived to be beneficial.
Trial protocol suitability is rarely addressed; however, we found this to be fundamental as it has a direct impact on the execution and outcomes of the work. Our results indicate that preliminary discussions and reviewing of the protocol with trial staff are most helpful in increasing protocol suitability. We concur with the interviewees and consider the involvement of operationally experienced staff to be most useful.
To mitigate informed consent challenges we suggest making use of the flexibility that the GCP guideline offers as well as identifying and tackling challenges prospectively. We deem that clarifying guidance for informed consent issues in resource-limited settings would be helpful for trial staff.
To allow for such measures, allocating enough time for trial preparation and enabling of the uptake of feedback and information on context at an early stage are a requisite. We found that such prospective planning would increase implementability, efficiency and quality in the long run.
Due to a general lack of research on trial practices and our small sample size more research is needed in order to validate and strengthen some of these findings. Trial staff members proved to be a valuable source of information to investigate trial practices. We consider the incorporation of sponsors` perceptions and interests on top of investigations of the study site as important for future research.