ReviewAlcoholism, clinical and experimental research2018
Overcoming the "Valley of Death" in Medications Development for Alcohol Use Disorder.
Review in Alcoholism, clinical and experimental research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses 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
26 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Translating medication effects for alcohol use disorder across preclinical, human laboratory, and clinical trial outcomes using meta-analysis.Translational psychiatry · 2025Pooled it
- Are medication effects on subjective response to alcohol and cue-induced craving associated? A meta regression study.Psychopharmacology · 2023Pooled it
- The neural and psychophysiological effects of cannabidiol in youth with alcohol use disorder: A randomized controlled clinical trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- N-acetylcysteine for youth cannabis use disorder: randomized controlled trial main findings.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- A practice quit model to test early efficacy of medications for alcohol use disorder in a randomized clinical trial.Psychopharmacology · 2024Trial
- N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- Using naltrexone to validate a human laboratory test system to screen new medications for alcoholism (TESMA)- a randomized clinical trial.Translational psychiatry · 2023Trial
- Trial
- The Interplay Between Subjective Response to Alcohol, Craving, and Alcohol Self-Administration in the Human Laboratory.Alcoholism, clinical and experimental research · 2019Trial
- The alcohol cue-exposure paradigm as a screening tool for alcohol use disorder medication development: A critical review.Alcohol, clinical & experimental research · 2025Review
- High hopes, hard realities: cannabidiol shows no acute effects in youth with alcohol use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Characterizing alcohol cue reactive and non-reactive individuals with alcohol use disorder.Addictive behaviors · 2024Article
- Social Media as Pharmacovigilance: The Potential for Patient Reports to Inform Clinical Research on Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists for Substance Use Disorders.Journal of studies on alcohol and drugs · 2024Article
- Testing pharmacotherapies for alcohol use disorder with cue exposure paradigms: A systematic review and quantitative synthesis of human laboratory trial methodology.Alcohol, clinical & experimental research · 2023Review
- A Meta-Regression of Trial Features Predicting the Effects of Alcohol Use Disorder Pharmacotherapies on Drinking Outcomes in Randomized Clinical Trials: A Secondary Data Analysis.Alcohol and alcoholism (Oxford, Oxfordshire) · 2022Review
- Applying the Addictions Neuroclinical Assessment to derive neurofunctional domains in individuals who use methamphetamine.Behavioural brain research · 2022Article
- Translational opportunities in animal and human models to study alcohol use disorder.Translational psychiatry · 2021Review
- Sudden cessation of fluoxetine before alcohol drinking reinstatement alters microglial morphology and TLR4/inflammatory neuroadaptation in the rat brain.Brain structure & function · 2021Article
- The future of translational research on alcohol use disorder.Addiction biology · 2021Article
- Do behavioral pharmacology findings predict clinical trial outcomes? A proof-of-concept in medication development for alcohol use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
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Authors and funding
4 authors.
Funding
Abstract
As the development of novel pharmacotherapies for alcohol use disorder (AUD) has been slow, the discovery and testing of more efficacious pharmacotherapies for AUD represent a high priority research area. In fact, the transition from preclinical to clinical testing of novel compounds has been termed the "valley of death" in medications development. One key obstacle consists of the lack of an articulated set of goals for each stage of medications development. Specifically, the knowledge outputs required to make the transition from safety testing, to early efficacy detection, to confirming clinical efficacy remain unclear, and this is despite a great deal of interest and substantial financial investment in developing novel therapeutics for AUD. This qualitative critical review seeks to draw parallels and lessons from the well-established stage model for behavioral therapies research with alcohol and other substance use disorders and to apply these insights into AUD pharmacotherapy development. We argue that human laboratory models and/or pilot randomized controlled trials should serve as intermediaries in the transition from preclinical studies to large, and costly, randomized controlled efficacy trials. The relative strengths and weaknesses of pilot clinical trials versus human laboratory studies for bridging the "valley of death" are discussed and explored via a Monte Carlo data simulation study. Multiple permutations of suitable research designs informed by the behavioral therapies development model are discussed with the overall goal of promoting consilience and maximizing efficiency across all phases of clinical testing of novel AUD pharmacotherapies.
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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.