Design of the PharmTrain fellowship programmeParticipants

Participants in this study were assessors from the three NRAs, Ghana (FDA Ghana), Tanzania (Tanzania Medicines and Medical Devices Authority), and Zimbabwe (Medicines Control Authority of Zimbabwe) enrolled in a specialized training fellowship.

Implementation of the fellowship programme

Owing to pandemic-related constraints, the fellowship programme was conducted in two distinct phases (Supp. Fig. 1). Phase I, held in 2019, comprised an on-site workshop, completed by two participants from the NRAs of Ghana and Zimbabwe. Owing to COVID-19-related travel restrictions, the subsequent phase II in 2021 was conducted as an online course. Nine fellows from Ghana, Zimbabwe, and Tanzania were selected following the same standardized approach. Both phases involved trainings by BfArM experts in key regulatory competencies with a strong focus on clinical assessment in marketing authorization procedures, comprising approx. 200 h of lectures, discussions, and hands-on trainings in total (study time and homework not counted). The comparison of the pre- and the post-evaluation allowed conclusions to be drawn about the impact of the training on individual capacity.

Fellowship curriculum

The GHPP PharmTrain Fellowship Programme curriculum was developed with support of the WHO GCF. The framework guided the identification of essential competencies required for clinical assessors. The curriculum was tailored through a needs assessment to address specific training gaps in African NRAs with a strong focus on clinical assessment of marketing authorization applications, integrating hands-on assessments of dossiers to apply the newly gained knowledge practically. The modules of the curriculum were targeted to the specific needs as identified in the WHO framework and thus aligning with participant selection criteria. Ideal candidates were expected to possess a solid foundational knowledge while at the same time demonstrating potential for further development. Continuous feedback was incorporated to ensure the training remains relevant. Widely recognized international standards serve as a foundation for the training.

Duration

Ten weeks on-site or 13 weeks remote.

Terminal objective

By the end of the GHPP PharmTrain Fellowship Programme, clinical assessors from African NRAs will demonstrate advanced proficiency in assessing clinical data for marketing authorization procedures for new chemical entities (small molecules) in line with applicable international guidelines, effectively applying the principles of benefit/risk assessment, good clinical practice, bioequivalence, biometrics, pharmacokinetics, and regulatory science. Successful fellows should exhibit proficiency in part/all of the competencies as per the competency profile of clinical reviewers based on the GCF. They will possess the capability to mentor and train peers of their respective NRAs in alignment with global regulatory standards.

Learning objectives

Through hands-on assessments of clinical dossiers and expert lectures on the below listed topics, participants will achieve the overarching goal of demonstrating advanced proficiency in assessing clinical data and a thorough understanding of regulatory processes, thereby contributing to the effective regulation of new chemical entities within their respective NRAs.

Modules and topics covered

Regulatory Processes

– Overview of regulatory frameworks

– Structural information on regulatory processes

– Decision-making processes

– Transparency of regulatory processes

– Global health challenges and solutions

– Regulatory Preparedness in Public Health Emergencies

European Marketing Authorization Procedures

– Marketing Authorization procedures in the European Network

– The centralized procedure

– Post-marketing procedures

– Harmonization of regulatory processes

Nonclinical assessment

– Relevant basics in nonclinical assessment

Clinical assessment

– Approach to clinical assessment

– Assessment of efficacy

– Assessment of safety

– Benefit/risk assessment

– Good clincial practice/Ethics

– Types and designs of clinical studies

– Study endpoints

– The clinical dossier

– Assessment of the product information

– Fixed dose combinations

– Crosslinking with post marketing

Pharmacokinetics and bioequivalence

– Principals of pharmacokinetics

– Drug interactions

– Population pharmacokinetic analyses

– Bioanalytical methods

– Bioequivalence studies

Biometrics and statistics

– Statistical methods in clinical trials

– Data interpretation

Didactics and teaching methods

– Effective teaching strategies and didactics

– Online teaching methods

– Train-the-trainer principles

Learning activities

Learning activities included live sessions (in person or virtual) with BfArM or external experts, hands-on dossier assessments, specific tasks, and practical exercises between sessions, follow-up webinars for discussion, and written feedback on practical exercises. Fellows also attended EMA committee meetings and had study visits to project partners such as the WHO Headquarters.

GHPP PharmTrain fellowship and the role of the GCF

The GCF served as an essential tool for the design of the GHPP PharmTrain fellowship for African clinical assessors. It provided the foundation for creating a candidate profile, selecting participants, developing the curriculum, and evaluating the success of the programme (Fig. 1). The GCF delineates the knowledge, skills, and behaviour expected of regulatory authority staff. It aims to establish a global standard to systematically enhance regulatory employees' competencies and, consequently, regulatory systems. The GCF has evolved since 2018 through updates and pilot testing. Our analysis employed GCF version 1.2 in PharmTrain phase 1, organizing competencies into mandatory, core, and role-specific categories, and version 1.5.2 in PharmTrain phase 2 (Supp. Fig. 1A), which introduced meta-competencies and specific practice activities (Supp. Fig. 1B). The 2023 GCF final edition further refined these categories, but our study precedes its formal release, limiting our analysis to draft versions (WHO 2023). The GCF consistently categorizes competencies into three skill levels, aligning with the Dreyfus skill acquisition model for proficiency assessment (Dreyfus 2016). The GCF facilitated an iterative process of application and refinement for training programmes. Competencies defined by the GCF were evaluated, optimized for the programmes objectives, and used to design the training program, candidate selection, and evaluation of the programme.

Fig. 1

Overview of the iterative cycle for the application and refinement of application of the WHO GCF for training programmes for regulators. The competencies of the GCF are first evaluated, narrowed down, and optimized with regard to the objectives and curriculum of the training programme. On the basis of these selections, a GCF-based survey (filled by both candidates and trainees) is conducted to identify appropriate candidates that fit the target of the programme. The candidates complete the training programme and return to their NRA. The impact of the training is monitored over a defined period of time by means of GCF surveys. Evaluation thus allows conclusions to be drawn about the success of the training itself, thereby reflecting on the general suitability of the GCF for training programmes and recommending adjustments of the GCF for training programmes

Identification of key competencies and development of a candidate profile

The target profile of programme candidates was created using the listed competencies in the GCF (for schematic process see Supp. Fig. 2). To refine the extensive framework to focus on the objectives of capacity development within PharmTrain and therefore determine the proficiencies that together form a suitable candidate profile, key competencies required for regulatory assessors were identified and discussed collaboratively by both junior regulatory reviewers and experienced (senior) clinical reviewers (Supp. Tables 1–6). To identify the most relevant competencies from each category, the competencies listed in the GCF were first prioritized as low, medium, or high according to their importance as prerequisites for qualified trainees. The obligatory skill level was then defined as basic, competent, or proficient/expert for the prioritized competencies (high). The resulting competencies at defined skill levels were regarded as crucial for ensuring the candidates have the required foundations to assimilate the course contents most effectively and subsequently communicate them to others in their role as a trainer according to the train-the-trainer principle.

Selection process of candidates

It is a pivotal principle for the delivery of an impactful programme to build on the existing local expertise and regional strength (Kerpel-Fronius et al. 2015; Owusu Sekyere et al. 2022). In line with the African Medicines Regulatory Harmonisation Initiative’s guiding principles, NRAs with RCORE (Regional Centres of Regulatory Excellence) status were selected as partners in the PharmTrain fellowship to facilitate the train-the-trainer concept because, by definition, RCOREs are expected to provide training and/or delivery of regulatory services to other African NRAs (AUDA-NEPAD 2016).

Moreover, the selection of authorities was a strategic decision to promote the further transfer of knowledge gained from the North–South cooperation of the fellowship through South–South collaboration since they are widely distributed across the continent. To maximize the impact of the capacity development programme, it was essential to select qualified participants within each RCORE who would be able to act as multipliers (train–the-trainer) of the knowledge and experience they have acquired at the national, regional, and supra-regional level. This required the assessors to be sufficiently qualified to absorb and disseminate the new knowledge and skills. On the basis of the developed target candidate profile, a survey (GS) was generated for the applicants, covering the prerequisite competencies at the required skill level. Each question was directed to the applicant and his or her supervisor. For a quantitative evaluation, a rating of the competencies in a range from 1 (not applicable) to 10 (very applicable) was introduced. In this manner, subjectivity was mitigated. It is important to underscore that the objective did not entail universal attainment of a high score, but rather, it sought to establish a requisite foundational proficiency that provided a springboard for subsequent advancement. These candidates could be expected to share their acquired competencies with colleagues according to the train-the-trainer principle. For the assessment process, each NRA was invited to select a minimum of four applicants in line with the stated aims of the fellowship and the responsibilities of the candidate in the authority. To guide the training institution’s decision, the applicants submitted further documents such as curricula vitae and motivation letters explaining their dedication to supporting sustainable capacity development in their authority/region. These documents allowed for the assessment of the applicants’ educational background as well as work experience and current roles in the authority. For phase I (on-site), two candidates from two NRAs were selected, and for phase II (online), nine candidates from three NRAs participated in the fellowship.

Evaluation of the fellowship programme

Participants were required to complete a series of surveys and assessments both prior to the commencement of the training and upon its conclusion. The collected data were subsequently analysed to evaluate the impact of the training on GCF competencies.

InstrumentsSurveys

Two sets of surveys, GSPRE and GSPOST, were utilized to evaluate the fellowship programme. The GSPRE survey was administered before the commencement of the training, while the GSPOST survey was administered six months after the fellowship. Both the fellows and their supervisors completed the GS surveys. Detailed records of response rates and handling of incomplete data were maintained to ensure data integrity.

The surveys assessed various competency categories using the GCF. GCF Version 1.2 included categories such as Mandatory Workplace Competencies (MWC), Core Competencies (CC) and Role-Specific Competencies (RSC). In contrast, GCF Version 1.5.2b restructured these categories into Practice Activities for Reviewers (PA), Meta-Competencies (MC), Functional Competencies (FC), and Role-Specific Competencies (RSC).

Self-evaluation scores were divided by the supervisor evaluation scores to determine the Level of Agreement (LoA) between fellows and supervisors. A value of 1 indicated perfect agreement. The pre-fellowship (GSPRE) and post-fellowship (GSPOST) responses were compared to evaluate the practical impact of the training on the fellows’ roles as assessors.

Knowledge tests

A pre-training test (TPRE), consisting of 32 questions on general pharmacology, statistics, clinical assessment, and didactics, reflecting the content of the forthcoming training, was conducted to establish the baseline knowledge of participants. The maximum achievable score on this test was 100 points. A follow-up test (TPOST) was conducted after the fellowship to assess changes in theoretical knowledge. The results were analysed to additionally assess the effectiveness of the training programme.

Data analysis

Descriptive statistics were calculated for the survey scores and knowledge test scores. Paired t-tests were conducted to compare pre- and post-fellowship survey results (GSPRE vs. GSPOST) and knowledge test scores (TPRE vs. TPOST). The Level of agreement (LoA) was analysed to evaluate the consistency between fellows’ self-assessments and supervisors’ evaluations.

All results were reported as mean + SD. Significance was tested using a two-way-ANOVA + Bonferroni multiple comparison test. All data analyses and statistical operations were performed using Graphpad Prism (Graphpad Software Inc., San Diego, USA).