Evidence map›Paper›PMID 42287260›Full record

ArticleClinical and translational science2026

Interpretation of Chemistry, Hematology and Coagulation Laboratory Results in Early-Phase Clinical Pharmacology Trials; a Retrospective Analysis Based on the Placebo Arm of Randomized-Controlled Trials.

Jannik Rousel, Tessa Niemeyer-van der Kolk, Matthijs Moerland, Robert Rissmann, Naomi B Klarenbeek, Maurits F J M Vissers, Jacobus Burggraaf

Abstract read
In one paragraph

Article in Clinical and translational science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Jannik RouselCentre for Human Drug Research, Leiden, the Netherlands.ORCID 0000-0003-0986-3753
Tessa Niemeyer-van der KolkCentre for Human Drug Research, Leiden, the Netherlands.
Matthijs MoerlandCentre for Human Drug Research, Leiden, the Netherlands.
Robert RissmannCentre for Human Drug Research, Leiden, the Netherlands.
Naomi B KlarenbeekCentre for Human Drug Research, Leiden, the Netherlands.
Maurits F J M VissersCentre for Human Drug Research, Leiden, the Netherlands.ORCID 0000-0001-7199-7301
Jacobus BurggraafCentre for Human Drug Research, Leiden, the Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Early-phase clinical trials focus heavily on demonstrating safety and tolerability of drug candidates. Clinical laboratory test results outside of reference intervals (RIs) are often interpreted as possible indicators of harm. However, values outside RIs do not necessarily constitute drug-induced adverse effects. This retrospective analysis aims to position results outside RIs as common phenomena during clinical pharmacology trials. For this, a retrospective analysis was performed on 37 commonly used blood-based hematology, chemistry and coagulation markers of 11.535 screened participants and patients at screening, and 888 placebo-randomized healthy participants from 88 trials performed at the Centre for Human Drug Research between 2005 to 2025. On average, participants with RI excursions during trial participation already show more extreme values at screening and baseline. Also, after having been medically screened, values outside RIs are still commonly observed in placebo-randomized participants. Results appear centered around the mean of individual participants. The frequency and extent of RI excursions is measurand-specific but generally within 0.7-1.3 times the RI. More significant excursions over 0.5-2.0 times the RI are observed, including for liver transferases, but comprise only 1.5% of all excursions. Diurnal variation impacts some hematological measurands resulting in RI excursion especially around through times. To conclude, an individual predisposition exists towards more extreme values challenging the applicability of RIs in a longitudinal setting. Results during trial conduct can best be interpreted compared to individual baselines. RI excursions remain common in placebo-randomized participants and are therefore poorly indicative of drug-induced adverse events when not considered in their full clinical context.

Indexed as

Blood Chemical AnalysisHematologic TestsRandomized Controlled Trials as TopicAdultBiomarkersBlood CoagulationBlood Coagulation TestsFemaleHematologyHumansMalePlacebosReference ValuesRetrospective StudiesBiomarkersPlacebosclinical trialshealthy participantslaboratory valuesplacebo

Identifiers

PMID42287260
PMCPMC13264141

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.