How do clinical study reports published by regulators differ from raw individual participant‑level datasets, and why does that matter for independent reanalysis?
Executive summary
Clinical study reports and regulator summaries are curated, document-level narratives and aggregated analyses of trials, while individual participant data (IPD) are the raw, participant‑level records that underlie those summaries; the two are complementary but not interchangeable, and access to IPD changes what independent reanalysis can detect about outcome definitions, missing data, subgroup effects, and selective reporting [1] [2] [3]. Understanding their differences—formatting, completeness, standardization, and accessibility—is central to whether independent teams can reproduce, challenge, or refine regulatory conclusions [4] [5].
1. What regulators’ reports typically provide versus what IPD contains
Regulatory submissions and clinical study reports synthesize trial conduct, statistical analyses, and results into structured narratives and tables intended for decision-making, whereas IPD are the participant‑by‑participant records of baseline characteristics, treatments, outcomes, and follow‑up that permit re‑derivation of results from first principles; IPD include the raw variables that make subgroup and interaction tests possible while reports usually present aggregated end points and pre-specified analyses only [1] [2] [3].
2. Why formatting and coding differences matter for independent reanalysis
IPD from different trials are often formatted, coded, and annotated inconsistently, a problem highlighted in training and guidance documents, and that heterogeneity forces reanalysts to spend substantial effort harmonizing definitions of exposures, outcomes, and covariates before any pooled analysis can be valid; without that harmonization, reanalyses risk comparing apples and oranges even if all IPD are available [4] [3] [6].
3. What independent reanalysis can gain from IPD that reports cannot provide
Access to IPD allows investigators to standardize outcome definitions, re‑run analyses under unified missing‑data assumptions, detect outliers, restore participants excluded in original reports, and explore participant‑level effect modifiers and interactions—capabilities repeatedly cited as reasons IPD meta‑analyses are considered the “gold standard” for some questions and can produce different or more nuanced clinical inferences than aggregate summaries [3] [7] [2].
4. Practical and methodological obstacles to obtaining and using IPD
Securing IPD is time‑consuming and resource‑intensive: retrieving, checking, and converting datasets may take more than a year, older or multisponsor trials may be hard to obtain, and not all IPD meta‑analyses meet reporting or methodological standards—factors that can introduce availability bias and limit the claimed advantages of IPD reanalysis [3] [8] [9].
5. Where summaries can mislead and why access to IPD is a corrective
Aggregate or report‑level data are more vulnerable to selective reporting and heterogeneous presentation (different effect measures, selective outcome choice), which can bias meta‑analyses; IPD mitigates many of these threats by enabling consistent re‑derivation of effect measures across studies, though IPD projects themselves must be conducted transparently because they are not immune to bias if data are missing or unavailable [10] [11] [9].
6. Trade‑offs: when IPD matters and when reports may suffice
Empirical comparisons show that IPD and aggregate‑data meta‑analyses sometimes yield similar conclusions, so the resource‑heavy pursuit of IPD is not always necessary; the decision to seek IPD should be driven by whether subgroup, interaction, harmonization, or missing‑data issues are central to the clinical question—areas where IPD offers unique value [12] [11].
7. Implications for transparency, trust, and regulatory practice
Greater availability of IPD and standardized metadata would improve reproducibility and allow independent teams to interrogate uncertainties that regulator reports summarize but cannot fully disclose; however, achieving that requires sustained policy, infrastructure, and quality‑control improvements because current IPD access and IPD‑MA practice vary in completeness and methodological rigor [4] [5] [9].