ReviewNature reviews. Drug discovery2011
Bridging the efficacy-effectiveness gap: a regulator's perspective on addressing variability of drug response.
Review in Nature reviews. Drug discovery, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 10 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
135 citing papers in PubMed, 10 syntheses or guidelines pooled it.
- Comprehensive safety analysis of adverse events associated with eptinezumab in migraine treatment.Scientific reports · 2025Pooled it
- Randomized Versus Real-World Evidence on the Efficacy and Toxicity of Checkpoint Inhibitors in Cancer in Patients with Advanced Non-small Cell Lung Cancer or Melanoma: A Meta-analysis.Targeted oncology · 2022Pooled it
- Framework for the synthesis of non-randomised studies and randomised controlled trials: a guidance on conducting a systematic review and meta-analysis for healthcare decision making.BMJ evidence-based medicine · 2022Pooled it
- Systematic review and meta-analysis: real-world data rates of deep remission with anti-TNFα in inflammatory bowel disease.BMC gastroenterology · 2021Pooled it
- What happens after randomised controlled trials? Uterine fibroids and ulipristal acetate: systematic review and meta-analysis of "real-world" data.Archives of gynecology and obstetrics · 2021Pooled it
- Intensive Monitoring Studies for Assessing Medicines: A Systematic Review.Frontiers in medicine · 2019Pooled it
- Benefits and Harms of Omalizumab Treatment in Adolescent and Adult Patients With Chronic Idiopathic (Spontaneous) Urticaria: A Meta-analysis of "Real-world" Evidence.JAMA dermatology · 2019Pooled it
- Use of the PRECIS-II instrument to categorize reports along the efficacy-effectiveness spectrum in an hepatitis C virus care continuum systematic review and meta-analysis.Journal of clinical epidemiology · 2018Pooled it
- Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data.BMJ (Clinical research ed.) · 2017Pooled it
- The patient perspective of diabetes care: a systematic review of stated preference research.The patient · 2014Pooled it
- Efficacy gap between phase II and subsequent phase III studies in oncology.British journal of clinical pharmacology · 2020Trial
- Acute and Longer-Term Outcomes Using Ketamine as a Clinical Treatment at the Yale Psychiatric Hospital.The Journal of clinical psychiatry · 2018Trial
- Impact of a community pharmacist-led medication review on medicines use in patients on polypharmacy--a prospective randomised controlled trial.BMC health services research · 2016Trial
- Older adults' satisfaction with a medication dispensing device in home care.Informatics for health & social care · 2013Trial
- The Patient-Centric Formulation Compass: A Proposed Bottom-Up Framework to Translate Population Insights into Product Design.The AAPS journal · 2026Review
- Real-world effectiveness of tofacitinib in monotherapy or in combination with csDMARDs in patients with rheumatoid arthritis: A collaboration between Dutch registries (TOFADUDAP study).Clinical rheumatology · 2026Article
- The replicability of real-world evidence for the surgical treatment of proximal humeral fractures in older patients evaluated using sceptical p-value.Scientific reports · 2026Observational
- A Cross-Sectional Survey of Evidence Needs for Medicinal Products in Europe With a Focus on Real-World Evidence.Pharmacoepidemiology and drug safety · 2026Article
- Bridging evidence worlds: policy and practice pathways for integrating clinical trials and real-world data in drug development and HTA.Frontiers in pharmacology · 2026Article
- Persistent clinical attrition does not establish animal models as a root cause of drug-development failures.NAM journal · 2026Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug regulatory agencies should ensure that the benefits of drugs outweigh their risks, but licensed medicines sometimes do not perform as expected in everyday clinical practice. Failure may relate to lower than anticipated efficacy or a higher than anticipated incidence or severity of adverse effects. Here we show that the problem of benefit-risk is to a considerable degree a problem of variability in drug response. We describe biological and behavioural sources of variability and how these contribute to the long-known efficacy-effectiveness gap. In this context, efficacy describes how a drug performs under conditions of clinical trials, whereas effectiveness describes how it performs under conditions of everyday clinical practice. We argue that a broad range of pre- and post-licensing technologies will need to be harnessed to bridge the efficacy-effectiveness gap. Successful approaches will not be limited to the current notion of pharmacogenomics-based personalized medicines, but will also entail the wider use of electronic health-care tools to improve drug prescribing and patient adherence.
Indexed as
Identifiers
21720406What 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.