A Scoping Review Protocol of the Efficacy and Safety of High-Dose Intravenous Vitamin C in the Treatment of Advanced Solid Tumors in African populations

Rationale for scoping review

Existing studies are largely concentrated in North America, Europe, and parts of Asia, with limited relevance to the sociocultural, genetic, and healthcare infrastructure realities of African patients. Africa’s public health sector will benefit from adjunctive treatments like HDIVC, which offer potential benefits in mitigating treatment-related side effects, enhancing quality of life, and providing consistent, comprehensive oncology care. Synthesizing the current global and emerging local evidence will identify gaps in knowledge, underscore the need for context-specific evidence to inform tailored therapeutic interventions, and support the development of African-centered clinical guidelines.

Study design

This scoping review will adopt the Joanna Briggs Institute (JBI) methodological framework for scoping reviews and adhere to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist for reporting (Hadie, 2024). These frameworks provide transparency, rigor, and reproducibility in scoping reviews by clearly articulating the processes for identifying, selecting, and synthesizing literature. This review also aligns with the enhanced methodology proposed by Arksey and O’Malley (Arksey & O’Malley, 2005) and later refined by Levac et al (Levac et al., 2010; Ouzzani et al., 2016), ensuring systematic rigor through six key steps ( Figure 1):

Figure 1. Six stages of conducting a scoping review.

Stage 1: Identifying the research question

The research question was developed using the technique suggested by Arksey and O’Malley (Arksey & O’Malley, 2005) and further refined by Levac et al. (Levac et al., 2010), which builds on Arksey and O’Malley’s framework, with guidance from subsequent enhancements. The proposed scoping review methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR, Figure 2) guidelines and checklist to allow us to make use of literature across study designs and in both peer-reviewed and grey literature. The process will involve five key stages and an optional sixth stage that we have included in our process.

Figure 2. PRISMA for Scoping Reviews (PRISMA-ScR) flowchart for study selection – A Scoping Review Protocol of the Efficacy and Safety of High-Dose Intravenous Vitamin C in the Treatment of Advanced Solid Tumors in African populations.

Source: Tricco et al. (2018).

The process will include: (1) Identifying the research question –clearly defining the purpose, concepts, and target population to maintain a balance between breadth and focus; (2) Identifying relevant studies – developing an iterative, comprehensive search strategy in collaboration with an information specialist, covering both peer-reviewed and grey literature; using predefined keywords and Boolean operators (3) Study selection – applying well-defined inclusion and exclusion criteria with independent screening of titles and abstracts and full articles by two reviewers, including pilot testing to ensure consistency; (4) Charting the data – using a standardized and iteratively refined extraction form to capture key study characteristics and contextual information; (5) Collating, summarizing, and reporting results – analyzing and presenting findings through descriptive numerical summaries, thematic synthesis, and interpretation of implications for research, policy, and practice; and (6) Consultation with stakeholders – engaging relevant experts and knowledge users to validate findings, identify gaps, and guide dissemination and inform implications for research and practice.

Research Sub-questions:

This study will use the Population, Intervention, Comparison, Outcomes, and Timeline (PICOT) format to align the study selection with the research question. This study’s applied PICOT framework is shown in Table 1. The timeline for this study will span 12 weeks from 01 October 2025 to 31 December 2025, and eligible studies will be from 2000 to 2025. The use of high-dose intravenous vitamin C as a potential adjunct in oncology started to receive renewed scientific attention in the early 2000s following the pioneering pharmacokinetic studies conducted by NIH researchers that showed intravenous but not oral vitamin C could achieve pharmacologic plasma concentrations with potential cytotoxic effects on tumor cells. Prior to 2000, most studies were anecdotal or lacked a thorough clinical approach. Over the past 20 years, there has been an increasing push to improve the infrastructure for clinical research in low- and middle-income countries (LMICs) and Africa (Böttger et al., 2021).

Stage 2: Identifying relevant studies

We will comprehensively search electronic databases (PubMed, ScienceDirect, Scopus, and Google Scholar) and grey literature sources for studies published between 2000 and 2025. An initial exploratory search strategy based on the PICOT framework will be developed on PubMed to determine some relevant terms to the research question. However, there is no comparator for this study hence PIOT framework will be used. A second search strategy will be developed using the most relevant Medical Subject Headings (MeSH) terms, while some keywords will be searched in the title, abstract, and subject headings of the other electronic databases. Additional grey literature will be searched through cancer research institutes’ organizational reports, and manual searching of reference lists from included studies, including consulting websites such as the World Health Organization (WHO) and the United Nations (UN). The initial search strategy in the electronic databases is stated in Table 2.

Stage 3: Study selection of eligible studies

To ensure a rigorous selection process, we will employ the PIOT framework (Population Intervention Outcome Time) as a guide for title and abstract screening, with the two reviewers working independently. It is anticipated that the selection of studies for the review will be completed within 12 weeks, and this process will adhere to the guidelines provided by the PRISMA-ScR checklist. Once all identified records have been extracted from all databases, duplicates will be eliminated using the EndNote X9 (Clarivate) software. Rayyan, a reviewing platform, will be used to execute the entire selection process to facilitate collaboration between the reviewers to maintain transparency and streamline the reviewing process. Any discrepancies between the two reviewers during the screening and selection stages will be resolved through discussion with an expert in cancer care to reach an agreement.

Eligibility criteria

Titles and abstracts will be screened for eligibility by two independent reviewers based on the inclusion criteria:

Inclusion criteria:

Exclusion criteria:

Stage 4: Data charting process

A standardized data extraction form will be developed and piloted to ensure clarity and consistency. The form will capture key details shown in Table 3.

Stage 5: Data collation, summarization, and reporting

The key findings across studies will be synthesized. The NVivo software will be used for qualitative synthesis of data. Qualitative data will be summarized narratively in themes. Descriptive statistics will be used for quantitative outcomes, where applicable, and presented in tables and figures. A PRISMA-ScR flow diagram would be used to illustrate the selection process.

Quality assessment of included studies

Quality assessment is not a primary focus in the scoping review. The study designs of included studies, such as qualitative, quantitative, and mixed methods, will be described to improve the quality of scoping reviews by enhancing transparency and uniformity in reporting. This assessment will help contextualize the strength of the evidence and identify methodological gaps. There will be no risk of bias assessment for this scoping review.

Stage 6: Consultation

Stakeholders, including researchers, policymakers, and alternative medicine practitioners, will be consulted to validate and interpret the findings of this scoping review. Though these stakeholders have not directly contributed to the design of this review, they will be consulted and involved in interpreting our findings for practical and evidence-based decision-making.

Strengths and limitations

The review will follow a well-established scoping review methodology using the Arksey and O’Malley framework, refined by the Levac et al framework. The selection of articles will cover studies published in the last two decades (2000 –2025), synthesizing old and current evidence from the literature. The inclusion of grey literature strengthens our review by reducing publication bias and enhancing the comprehensiveness of our findings.

However, studies un-indexed in languages other than English, in the consulted databases, and in grey literature will be omitted from the review.