Evidence mapPaperPMID 30509294Full record

ReviewJournal of translational medicine2018

Reviewing the role of healthy volunteer studies in drug development.

Joyson J Karakunnel, Nam Bui, Latha Palaniappan, Keith T Schmidt, Kenneth W Mahaffey, Briggs Morrison, William D Figg, Shivaani Kummar

Open access · goldAbstract readReview
In one paragraph

Review in Journal of translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
4.2field-weighted citation impact, top 6% of its field
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

23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Modulation of premotor cortex response to sequence motor learning during escitalopram intake.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
    Trial
  7. Safety of healthy subjects in first-in-human multiple-dose studies: A pooled analysis.International journal of clinical pharmacology and therapeutics · 2021
    Trial
  8. Review
  9. Review
  10. Article
  11. Observational
  12. Article
  13. Article
  14. Article
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  19. Physical Rehabilitation Programs for Bedridden Patients with Prolonged Immobility: A Scoping Review.International journal of environmental research and public health · 2022
    Article
  20. Article
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

8 authors at 4 institutions in 1 country.

Joyson J KarakunnelArcus Biosciences, Inc., 3928 Point Eden Way, Hayward, CA, 94545, USA. jkarakunnel@arcusbio.com.
Nam BuiStanford Cancer Institute, 875 Blake Wilbur Drive, Stanford, CA, 94305, USA.
Latha PalaniappanDepartment of Medicine, Stanford University School of Medicine, 900 Blake Wilbur Drive, Room W200, 2nd Floor MC 5358, Stanford, CA, 94304, USA.
Keith T SchmidtClinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
Kenneth W MahaffeyStanford Center for Clinical Research (SCCR), Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Grant S-102, Stanford, CA, 94305, USA.
Briggs MorrisonSyndax, 211 East 43rd Street, #900, New York, NY, 10017, USA.
William D FiggClinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
Shivaani KummarStanford Cancer Institute, 875 Blake Wilbur Drive, Stanford, CA, 94305, USA.
National Cancer Institute · USStanford Cancer InstituteCenter for Clinical Research (United States) · USStanford University · US

Funding

Drug Development for Prostate CancerZIABC010547 · DIVISION OF BASIC SCIENCES - NCI · 2025 to 2025
$783k
6 · The paper itself

Abstract

backgroundWith the exception of genotoxic oncology drugs, first-in-human, Phase 1 clinical studies of investigational drugs have traditionally been conducted in healthy volunteers (HVs). The primary goal of these studies is to investigate the pharmacokinetics and pharmacodynamics of a novel drug candidate, determine appropriate dosing, and document safety and tolerability. MAIN BODY: When tailored to specific study objectives, HV studies are beneficial to manufacturers and patients alike and can be applied to both non-oncology and oncology drug development. Enrollment of HVs not only increases study accrual rates for dose-escalation studies but also alleviates the ethical concern of enrolling patients with disease in a short-term study at subtherapeutic doses when other studies (e.g. Phase 2 or Phase 3 studies) may be more appropriate for the patient. The use of HVs in non-oncology Phase 1 clinical trials is relatively safe but nonetheless poses ethical challenges because of the potential risks to which HVs are exposed. In general, most adverse events associated with non-oncology drugs are mild in severity, and serious adverse events are rare, but examples of severe toxicity have been reported. The use of HVs in the clinical development of oncology drugs is more limited but is nonetheless useful for evaluating clinical pharmacology and establishing an appropriate starting dose for studies in cancer patients. During the development of oncology drugs, clinical pharmacology studies in HVs have been used to assess pharmacokinetics, drug metabolism, food effects, potential drug-drug interactions, effects of hepatic and renal impairment, and other pharmacologic parameters vital for clinical decision-making in oncology. Studies in HVs are also being used to evaluate biosimilars versus established anticancer biologic agents.

conclusionA thorough assessment of toxicity and pharmacology throughout the drug development process is critical to ensure the safety of HVs. With the appropriate safeguards, HVs will continue to play an important role in future drug development.

Indexed as

Drug DevelopmentHealthy VolunteersAntineoplastic AgentsClinical Trials as TopicHumansMedical OncologyAntineoplastic AgentsBioequivalenceFirst-in-humanHealthy volunteerMedical ethicsPharmacodynamicPharmacokineticPhase 1SafetyToxicity

Identifiers

PMID30509294
PMCPMC6278009
OpenAlexW2902907673

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.