Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study

Fares Alahdab, Wigdan Farah, Jehad Almasri, Patricia Barrionuevo, Feras Zaiem, Raed Benkhadra, Noor Asi, Mouaz Alsawas, Yifan Pang, Ahmed T. Ahmed, Tamim Rajjo, Amrit Kanwar, Khalid Benkhadra, Zayd Razouki, Mohammad H Murad, Zhen Wang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective: To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. Methods: We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta-analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. Results: We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12-3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow-up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow-up or the test for publication bias. Conclusion: Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution.

Original languageEnglish (US)
Pages (from-to)278-283
Number of pages6
JournalMayo Clinic Proceedings
Volume93
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Meta-Analysis
Epidemiologic Studies
Randomized Controlled Trials
Publication Bias
Therapeutics
Inpatients
Outpatients
Morbidity
Equipment and Supplies
Mortality
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions : A Meta-Epidemiologic Study. / Alahdab, Fares; Farah, Wigdan; Almasri, Jehad; Barrionuevo, Patricia; Zaiem, Feras; Benkhadra, Raed; Asi, Noor; Alsawas, Mouaz; Pang, Yifan; Ahmed, Ahmed T.; Rajjo, Tamim; Kanwar, Amrit; Benkhadra, Khalid; Razouki, Zayd; Murad, Mohammad H; Wang, Zhen.

In: Mayo Clinic Proceedings, Vol. 93, No. 3, 01.03.2018, p. 278-283.

Research output: Contribution to journalArticle

Alahdab, F, Farah, W, Almasri, J, Barrionuevo, P, Zaiem, F, Benkhadra, R, Asi, N, Alsawas, M, Pang, Y, Ahmed, AT, Rajjo, T, Kanwar, A, Benkhadra, K, Razouki, Z, Murad, MH & Wang, Z 2018, 'Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study', Mayo Clinic Proceedings, vol. 93, no. 3, pp. 278-283. https://doi.org/10.1016/j.mayocp.2017.10.020
Alahdab, Fares ; Farah, Wigdan ; Almasri, Jehad ; Barrionuevo, Patricia ; Zaiem, Feras ; Benkhadra, Raed ; Asi, Noor ; Alsawas, Mouaz ; Pang, Yifan ; Ahmed, Ahmed T. ; Rajjo, Tamim ; Kanwar, Amrit ; Benkhadra, Khalid ; Razouki, Zayd ; Murad, Mohammad H ; Wang, Zhen. / Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions : A Meta-Epidemiologic Study. In: Mayo Clinic Proceedings. 2018 ; Vol. 93, No. 3. pp. 278-283.
@article{99981b4846204fe4810c403cd621450b,
title = "Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study",
abstract = "Objective: To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. Methods: We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta-analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. Results: We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37{\%}. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95{\%} CI, 2.12-3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow-up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow-up or the test for publication bias. Conclusion: Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution.",
author = "Fares Alahdab and Wigdan Farah and Jehad Almasri and Patricia Barrionuevo and Feras Zaiem and Raed Benkhadra and Noor Asi and Mouaz Alsawas and Yifan Pang and Ahmed, {Ahmed T.} and Tamim Rajjo and Amrit Kanwar and Khalid Benkhadra and Zayd Razouki and Murad, {Mohammad H} and Zhen Wang",
year = "2018",
month = "3",
day = "1",
doi = "10.1016/j.mayocp.2017.10.020",
language = "English (US)",
volume = "93",
pages = "278--283",
journal = "Mayo Clinic Proceedings",
issn = "0025-6196",
publisher = "Elsevier Science",
number = "3",

}

TY - JOUR

T1 - Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions

T2 - A Meta-Epidemiologic Study

AU - Alahdab, Fares

AU - Farah, Wigdan

AU - Almasri, Jehad

AU - Barrionuevo, Patricia

AU - Zaiem, Feras

AU - Benkhadra, Raed

AU - Asi, Noor

AU - Alsawas, Mouaz

AU - Pang, Yifan

AU - Ahmed, Ahmed T.

AU - Rajjo, Tamim

AU - Kanwar, Amrit

AU - Benkhadra, Khalid

AU - Razouki, Zayd

AU - Murad, Mohammad H

AU - Wang, Zhen

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Objective: To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. Methods: We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta-analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. Results: We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12-3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow-up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow-up or the test for publication bias. Conclusion: Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution.

AB - Objective: To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. Methods: We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta-analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. Results: We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12-3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow-up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow-up or the test for publication bias. Conclusion: Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution.

UR - http://www.scopus.com/inward/record.url?scp=85042200050&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042200050&partnerID=8YFLogxK

U2 - 10.1016/j.mayocp.2017.10.020

DO - 10.1016/j.mayocp.2017.10.020

M3 - Article

C2 - 29477781

AN - SCOPUS:85042200050

VL - 93

SP - 278

EP - 283

JO - Mayo Clinic Proceedings

JF - Mayo Clinic Proceedings

SN - 0025-6196

IS - 3

ER -