Evidence map›Paper›PMID 31502253›Full record

ArticleClinical pharmacology and therapeutics2019

Drug-Placebo Additivity in Randomized Clinical Trials.

Kathryn T Hall, Joseph Loscalzo

Abstract read
In one paragraph

Article in Clinical pharmacology and therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Trial
  2. Placebo-response inflation in supportive oncology symptom trials: mechanisms, methodological challenges, and design implications.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Review
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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

2 authors.

Kathryn T HallDivision of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Joseph LoscalzoDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Funding

TRANSLATIONAL PHARMACOLOGY COREP50GM107618 · NIGMS · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2014 to 2018
$10.8M
Center for Integrated Approaches to Undiagnosed DiseasesU01HG007690 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2014 to 2022
$10.4M
TRAINING IN CARDIOVASCULAR BIOLOGYT32HL007382 · NHLBI · UNIVERSITY OF CINCINNATI · PI SCHWARTZ, ARNOLD · 1985 to 2012
$5.9M
GPx-3 and Peroxide Flux in the Endothelial CellR37HL061795 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2007 to 2016
$4.3M
PLATELET DERIVED REACTIVE OXYGEN SPECIES AND PLAQUER01HL061795 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 1998 to 2006
$1.6M
Epidemiological, pharmacogenomic and clinical impact of catechol-O-methyltransferase on cardiovascular diseaseK01HL130625 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI HALL, KATHRYN TAYO · 2016 to 2021
$921k
NHGRI NIH HHS U01 HG007690NHLBI NIH HHS K01 HL130625NHLBI NIH HHS R01 HL061795NHLBI NIH HHS R37 HL061795NIGMS NIH HHS P50 GM107618
6 · The paper itself

Abstract

In randomized clinical trials (RCTs), it is assumed that nonspecific effects beyond action of pharmacological agents are roughly equivalent in drug and placebo treatment groups. Hence, since the inception of RCTs, drug efficacy is determined by comparing outcomes in active to those in placebo control arms. However, quantitation of efficacy is based on an unproven assumption, that drug and placebo responses are always additive. Response to treatment in RCTs can be differentially influenced by the perturbing effects of patient expectations, side effects, and pharmacogenomic interactions in both drug and placebo arms. Ability to control for these effects requires understanding of when and where they arise, how to mitigate, analyze, and even leverage their impact. Here, we examine three factors that influence additivity: expectation, side effects, and pharmacogenomics. Furthermore, to provide novel insights into nonadditivity and solutions for managing it, we introduce systems pharmacogenomics, a network approach to integrating and analyzing the effects of the numerous interacting perturbations to which a patient is exposed in RCTs.

Indexed as

Placebo EffectRandomized Controlled Trials as TopicResearch DesignDrugs, InvestigationalHumansPharmacogeneticsTreatment OutcomeDrugs, Investigational

Identifiers

PMID31502253
PMCPMC7168700

What OpenQuestion holds

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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.