Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec:30:35-41.
doi: 10.1016/j.copsyc.2019.01.009. Epub 2019 Jan 28.

Methods to reduce the incidence of false negative trial results in substance use treatment research

Rachel L Tomko  1 , Erin A McClure  2 , Lindsay M Squeglia  2 , Hayley Treloar Padovano  3 , Aimee L McRae-Clark  2 , Nathaniel L Baker  4 , Matthew J Carpenter  2 , Kevin M Gray  2
Affiliations
Review

Methods to reduce the incidence of false negative trial results in substance use treatment research

Rachel L Tomko et al. Curr Opin Psychol. 2019 Dec.

Abstract

Treatment development and evaluation for substance use disorders are hindered when randomized controlled trials fail to show a treatment effect when one exists. This manuscript provides an overview of addressable methodological factors that may contribute to incorrect trial results. The collection of remote, naturalistic, real-time adherence and substance use data through ambulatory assessment methods in everyday life is presented as a partial solution. Other recommendations related to participant recruitment and selection, ensuring adequate consistency/fidelity and dose of treatment, and rigorously assessing clinical outcomes are discussed. With implementation of eligibility criteria verification, treatment adherence monitoring, and remote assessment of substance use and biomarkers, ambulatory assessment may help improve clinical trial success rates by improving precision, increasing reproducibility, and reducing the impact of methodological issues that may lead to inaccurate trial results.

PubMed Disclaimer

Conflict of interest statement

Rachel L. Tomko, Erin A. McClure, Lindsay M. Squeglia, Hayley Treloar Padovano, Aimee L. McRae-Clark, and Nathaniel L. Baker declare that they have no conflicts of interest. Matthew J. Carpenter and Kevin M. Gray have provided consultation to Pfizer, Inc.

References

    1. Kiluk BD, Carroll KM. New developments in behavioral treatments for substance use disorders. Curr Psychiatry Rep. 2013. November;15(12):420. - PMC - PubMed
    1. Volkow ND, Skolnick P. New medications for substance use disorders: challenges and opportunities. Neuropsychopharmacology. 2012. January;37(1):290–292. - PMC - PubMed

    1. Thomas DW, Burns J, Audette J, Carroll A, Dow-Hygelund C, Hay M. Clinical development success rates 2006–2015. San Diego: Biomedtracker/Washington, DC: BIO/Bend: Amplion; 2016. June Accessed 3/12/18 from http://www.amplion.com/clinical-development-success-rates.

      **This report examined success rates across >10,000 clinical trials and provides descriptive information on trial success rate across medical fields and phases of medication development. Psychiatry medications consistently had lower than average success rates at each phase of the medication development process. Success at Phase I was 6.2% for psychiatry and 9.6% for all indications. Success at Phase II was 24% for psychiatry and 31% for all indications. Success at Phase III was closer to the average with 56% of psychiatry medications and 58% of all medications having positive results. Studies using genetic biomarkers as inclusion criteria increased positive trial outcomes from 55% to 76%.

    1. Klemperer EM, Hughes JR, Naud S. Study characteristics influence the efficacy of substance abuse treatments: A meta-analysis of medications for alcohol use disorder. Drug and alcohol dependence. 2018. July 24.

      **In a meta-analysis of medications for alcohol use disorder, study characteristics accounted for almost half of the variance in treatment efficacy, with little consistency about which characteristics accounted for this effect. Findings highlight the need for comprehensively reporting study characteristics in clinical trials.

    1. Klemperer EM, Hughes JR, Naud S. Study characteristics influence the efficacy of substance abuse treatments: A meta-analysis of medications for smoking cessation. Nicotine & Tobacco Research.

      **In a meta-analysis of pharmacological treatments for tobacco use disorder, study characteristics accounted for 12% (nicotine patch) to 36% (buproprion) of variance in odds ratio. Findings highlight the need for comprehensively reporting study characteristics in clinical trials. The rate of abstinence in control conditions varied depending on study characteristics including funding source and date of publication, with industry funding and earlier dates of publication showing lower control group response rates for certain medications.

Publication types