A guide to prospective meta-analysis

The ‘Intervention’ of ‘Prospective Meta-analysis (PMA)’ in the ‘Evidence-based Medicine (EBM) Movement Improvement’ is a further pointer to the extant ‘Technical Difficulties’ with EBM [1]. It is pertinent to recall that, at the outset of the ‘Evidence-based Medicine (EBM) Movement’, only ‘Research Evidence’ mattered and all other previously relevant ‘Considerations’ were completely disregarded in the ‘Patient Care Decision-making Process’ [2]. Further progress was made with the development of the ‘Pyramid of Evidence’ which disposed the ‘Hierarchy and Quality of Research Evidence’ with ‘Randomized Controlled Trials (RCTs)’ occupying the Apex of the Pyramid [3]. The previously vacated ‘Clinical Expertise/ Expert Opinion’ was appropriately subsequently regarded as a ‘Form of Evidence’ but rated at the Bottom of the ‘Pyramid of Evidence’ as gleaned from various ‘EBM Models’ including the ‘GRADE Model’ [4-6]! Also, ‘Patient Perspectives’ previously disregarded were increasingly considered through the development of ‘Circles of Influence’: ‘Research Evidence Circle’, ‘Clinical Expertise Circle’ and ‘Patient Perspectives Circle’ [5, 7]. Over the years, the ‘EBM Movement Improvement Models’ have experienced remarkable reworking and lately, the ‘Circles of Influence’ were regarded as ‘Parameters’ and, therefore, the ‘EBM Movement Model’ as ‘Work In Progress’ for ‘Optimal Patient Care’ was disposed as ‘Multiparameter-based Medicine (MBM)’ [8].

The various ‘EBM Improvement Models’ have disposed the ‘Research Evidence Parameter’ as the ‘Critical Consideration’ that should undergird ‘Patient Care Decision-making Process’ and ‘Focus and Resources’ have, therefore, been largely deployed to improving the ‘Research Evidence’, the ‘Best Available Research Evidence (BARE)’, including introduction of ‘Systematic Reviews and Meta-analyses’ [9, 10]. There are, however, several ‘Technical Difficulties’ with ‘Research Evidence’ particularly the highly ‘Weighted Research Evidence’ accruing from ‘Systematic Reviews and Meta-analyses’ [11, 12]. Other relevant ‘Parameters’ (‘Circles of Influence’) are less ‘Investigated’ and ‘Evaluated’ for ‘Improvement Interventions’ in their ‘Quality Contribution’ to the ‘Patient Care Decision-making Process’. This is the ‘EBM Interventional Inequity’! Some of the ‘Technical Difficulties’ with the ‘Heavily Weighted Research Evidence’ from ‘Systematic Reviews and Meta-analyses’ include, among others, ‘Misleading and Conflicted Results’ [12], ‘Publication Bias’ [13,14], ‘Selection Criteria Bias’ [15], ‘Heterogeneity and Combinability Issues’ [16,17] and ‘Other Inconsistencies’ [1,18,19]! Other ‘Technical Difficulties’ include the appropriateness of using ‘Individual Data or Aggregate Data’ [20,21] and, indeed, the ‘Very Weak Power’ of several ‘Statistical Tools’ used in ‘Testing for Significance’ of any detected ‘Publication Bias’ and ‘Heterogeneity’ [9,10,22]! A previous ‘Communication’ has, in fact, criticized the ‘Heavily Weighted Research Evidence’ as the ‘Sine Qua Non’ for ‘Patient Care Decision-making Process’ and called for other ‘Parameters’ to receive appropriate and adequate deployment of ‘Interventions and Resources’ in the ‘EBM Movement Improvement’ [23]!

In furtherance of the ‘EBM Movement Improvement’ as manifest ‘Work In Progress’, there have been efforts to undertake ‘Prospective Meta-analyses (PMAs)’ as the ‘Next Generation of Research Evidence Improvement Interventions’ in contradistinction to the ‘Traditional/ ‘Retrospective’ Systematic Reviews and Meta-analyses’ [24-27]. The PMAs are presented as the ‘New Top-of-the Pyramid’ in the ‘Pyramid of Research Evidence’ [1]. The PMAs involve ‘Planned or On-going Studies’ which are ‘Identified’, ‘Determined’ and ‘Evaluated’ as ‘Eligible for Inclusion’ in the ‘Investigation’ of the ‘Common Research Question’ with the ‘Results’ of the ‘Included Studies’ unknown! This should eclipse the potentiality of ‘Analysis Bias’, foster ‘Research Collaboration’ or ‘Consortium Formation’ and guarantee ‘Access to Clinical Trial Registries’, ‘Research Grant/ Funding Bodies’ [28]! Sadly enough, the PMAs are already remarkably riddled with a plethora of ‘Technical Difficulties’ as were the ‘Traditional/ ‘Retrospective’ Systematic Reviews and Meta-analyses’! Some of the ‘Technical Difficulties’ include International Committee of Medical Journal Editors (ICMJE) ‘Requirements for Registration of the Planned and On-going Studies’ [29], lack of ‘Standardized Guidelines’ [30], ‘Heterogeneity Issues’ [17], the conduct of PMAs on ‘Individual Patient Data (IPD)’ or ‘Aggregate Data’ and the need for PRISMA-IPD (Preferred Reporting Items for Systematic Reviews and Meta-analysis-Individual Patient Data) [31]! Some Researchers have explored the possibility and value of ‘Living Prospective Meta-Analyses (Living PMAs)’ as part of the ‘EBM Movement Improvement’ [32]! Clearly, several ‘Interventions and Resources’ have been ploughed into the ‘Research Evidence Parameter’ to the neglect of other relevant ‘Parameters’ and yet ‘Increasing Technical Difficulties’ persist necessitating the need to address this ‘Interventional Inequity’ as an inevitable imperative!

Just as has been consistently and persistently undertaken for the ‘Pyramid of Evidence’ pertaining to ‘Research Evidence’, it is now clearly an urgent imperative to ‘Investigate’ and ‘Evaluate’ other ‘Parameters’(‘Circles of Influence’) for the possible development of ‘Parameter-related Pyramids of Evidence’. The ‘Other Parameters’ include ‘Clinical Expertise Parameter’/ ‘Expert Opinion Parameter’, ‘Patient Perspectives Parameter’, ‘Traditional/ Cultural Parameter’, ‘Family Parameter’, ‘Resource Availability Parameter’ just to dispose but a few! As a ‘Case-in-Point’, there has been an attempt to develop an ‘Individual Patient-related Pyramid of Evidence’ as a ‘Patient Perspectives Parameter-related Pyramid of Evidence’ [33]. At the base of this ‘Patient-related Pyramid of Evidence’ is ‘Self Tracking’ of ‘Patient Information/ Data’ and at the ‘Top’/ ‘Apex’ is the ‘System ID’. The ‘System Identification (System ID)’ is modelled after ‘Control Systems Engineering’, a Discipline in Engineering concerned with ‘Automatic Control Theory’ for ‘Design System’ in ‘Control Environments’ [34]. We have argued for the more critically determinant role and influence of ‘Clinical Expertise Parameter’ compared to ‘Research Evidence Parameter’ in ‘Patient Care Decision-making Process’. The imperative now is to develop a ‘Clinical Expertise Parameter-related Pyramid of Evidence’ that will be integrally useful for the practice of MBM [8]! Similarly, ‘Parameter-related Pyramids of Evidence’ should be ‘Investigated’, ‘Developed’ and ‘Evaluated’ for other identified and documented ‘Parameters’ in the MBM!!

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Professor Charles Osayande Eregie,
MBBS, FWACP, FMCPaed, FRCPCH (UK), Cert. ORT (Oxford), MSc (Religious Education),
Professor of Child Health and Neonatology, University of Benin, Benin City, Nigeria,
Consultant Paediatrician and Neonatologist, University of Benin Teaching Hospital, Benin City, Nigeria,
UNICEF-Trained BFHI Master Trainer,
ICDC-Trained in Code Implementation,
*Technical Expert/ Consultant on the FMOH-UNICEF-NAFDAC Code Implementation Project in Nigeria,
*No Competing Interests.