ArticleClinical pharmacology and therapeutics2016
"Threshold-crossing": A Useful Way to Establish the Counterfactual in Clinical Trials?
Article in Clinical pharmacology and therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Building External Control Arms From Patient-Level Electronic Health Record Data to Replicate the Randomized IMblaze370 Control Arm in Metastatic Colorectal Cancer.JCO clinical cancer informatics · 2021Trial
- Using Electronic Health Records to Derive Control Arms for Early Phase Single-Arm Lung Cancer Trials: Proof-of-Concept in Randomized Controlled Trials.Clinical pharmacology and therapeutics · 2020Trial
- The role of causal reasoning and directed acyclic graphs in multivariable regression: implications for evidence-based veterinary medicine.Frontiers in veterinary science · 2026Article
- The perfused liver utilisation study (PLUS): challenges and innovation in the evaluation of an emerging technology.Transplant international : official journal of the European Society for Organ Transplantation · 2026Article
- The role and value of real-world evidence in health technology decision-making in France, Germany, Italy, Spain, and the UK: insights on external control arms.International journal of technology assessment in health care · 2025Review
- Clopidogrel for Proteinuria Reduction in Focal Segmental Glomerulosclerosis: Phase 2 Trial Design.Kidney international reports · 2024Article
- Review
- A phase Ⅱ prospective trial of photobiomodulation therapy in limiting oral mucositis in the treatment of locally advanced head and neck cancer patients.World journal of otorhinolaryngology - head and neck surgery · 2022Article
- The Randomised Controlled Trial at the Intersection of Research Ethics and Innovation.Pharmaceutical medicine · 2022Article
- Chemical property prediction under experimental biases.Scientific reports · 2022Article
- Precision Reimbursement for Precision Medicine: Using Real-World Evidence to Evolve From Trial-and-Project to Track-and-Pay to Learn-and-Predict.Clinical pharmacology and therapeutics · 2022Review
- Emulating Control Arms for Cancer Clinical Trials Using External Cohorts Created From Electronic Health Record-Derived Real-World Data.Clinical pharmacology and therapeutics · 2022Article
- Designing Clinical Trials in Wilson's Disease.Hepatology (Baltimore, Md.) · 2021Article
- Optimizing subgroup selection in two-stage adaptive enrichment and umbrella designs.Statistics in medicine · 2021Article
- Randomized Controlled Trials Versus Real World Evidence: Neither Magic Nor Myth.Clinical pharmacology and therapeutics · 2021Review
- Virtual controls as an alternative to randomized controlled trials for assessing efficacy of interventions.BMC medical research methodology · 2021Review
- Expanded Access as a source of real-world data: An overview of FDA and EMA approvals.British journal of clinical pharmacology · 2020Article
- Are Novel, Nonrandomized Analytic Methods Fit for Decision Making? The Need for Prospective, Controlled, and Transparent Validation.Clinical pharmacology and therapeutics · 2020Review
- A roadmap to using historical controls in clinical trials - by Drug Information Association Adaptive Design Scientific Working Group (DIA-ADSWG).Orphanet journal of rare diseases · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
Abstract
A central question in the assessment of benefit/harm of new treatments is: how does the average outcome on the new treatment (the factual) compare to the average outcome had patients received no treatment or a different treatment known to be effective (the counterfactual)? Randomized controlled trials (RCTs) are the standard for comparing the factual with the counterfactual. Recent developments necessitate and enable a new way of determining the counterfactual for some new medicines. For select situations, we propose a new framework for evidence generation, which we call "threshold-crossing." This framework leverages the wealth of information that is becoming available from completed RCTs and from real world data sources. Relying on formalized procedures, information gleaned from these data is used to estimate the counterfactual, enabling efficacy assessment of new drugs. We propose future (research) activities to enable "threshold-crossing" for carefully selected products and indications in which RCTs are not feasible.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.