Evidence map›Paper›PMID 42508231›Full record

ReviewEBioMedicine2026

Common analysis pitfalls in longitudinal ctDNA studies: lead time, sensitivity and immortal time bias.

Dominik Hlauschek, Nadia Dandachi, Michael Gnant, Heather Parsons, Angela DeMichele, Ellen Heitzer, Gabriel Rinnerthaler, Marija Balic

Abstract readReview
In one paragraph

Review in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

8 authors.

Dominik HlauschekDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Austrian Breast and Colorectal Cancer Study Group [ABCSG], Vienna, Austria. Electronic address: dominik.hlauschek@abcsg.at.
Nadia DandachiDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Institute of Human Genetics, Diagnostic & Research Center for Molecular BioMedicine, Medical University of Graz, Graz, Austria.
Michael GnantAustrian Breast and Colorectal Cancer Study Group [ABCSG], Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Heather ParsonsClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Angela DeMicheleMedical Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ellen HeitzerInstitute of Human Genetics, Diagnostic & Research Center for Molecular BioMedicine, Medical University of Graz, Graz, Austria.
Gabriel RinnerthalerDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Austrian Breast and Colorectal Cancer Study Group [ABCSG], Vienna, Austria.
Marija BalicAustrian Breast and Colorectal Cancer Study Group [ABCSG], Vienna, Austria; Division of Oncology, Hillmans Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Circulating tumour DNA (ctDNA) has emerged as one of the most promising biomarkers in oncology, with potential applications from detection of minimal residual disease (MRD) and diagnosis to prognosis, treatment guidance, and response monitoring. This personal view critically examines recurring methodological and statistical pitfalls in ctDNA studies with longitudinal measurements. We highlight important issues with lead time definition and demonstrate that performance metrics like sensitivity and specificity are inherently time-dependent. Furthermore, we show why immortal time bias arises when classifying patients incorrectly as always positive, based on becoming positive during surveillance in MRD related studies. With a combination of toy data examples, simulations, and re-analysis of published data we provide practice-oriented guidance to support the design, analysis, and reporting of ctDNA trials. This viewpoint paper aims to sensitise the community and raise awareness of pitfalls in longitudinal ctDNA analysis, rather than offer definitive solutions-more evidence is needed first.

Indexed as

Biomarkers, TumorCirculating Tumor DNANeoplasmsBiasHumansLongitudinal StudiesNeoplasm, ResidualSensitivity and SpecificityTime FactorsBiomarkers, TumorCirculating Tumor DNActDNAImmortal time biasLead timeMRDSensitivitySpecificity

Identifiers

PMID42508231
PMCPMC13445507

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.