Evidence map›Paper›PMID 26547927›Full record

SynthesisJournal of the National Cancer Institute2016

Benefit, Risk, and Outcomes in Drug Development: A Systematic Review of Sunitinib.

Benjamin Carlisle, Nadine Demko, Georgina Freeman, Amanda Hakala, Nathalie MacKinnon, Tim Ramsay, Spencer Hey, Alex John London, Jonathan Kimmelman

Abstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 4 pooled it
–field-weighted citation impact
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

32 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Quantifying Patient Investment in Novel Neurological Drug Development.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Article
  15. Review
  16. Review
  17. Article
  18. The Beneficial Role of Sunitinib in Tumor Immune Surveillance by Regulating Tumor PD-L1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Article
  19. The role of microenvironment in tumor angiogenesis.Journal of experimental & clinical cancer research : CR · 2020
    Review
  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

9 authors.

Benjamin CarlisleStudies of Translation, Ethics and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montréal, QC, Canada (BC, ND, GF, AH, NM, SH, JK); University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada (TR); Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (SH); Department of Philosophy and Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, PA (AJL).
Nadine DemkoStudies of Translation, Ethics and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montréal, QC, Canada (BC, ND, GF, AH, NM, SH, JK); University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada (TR); Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (SH); Department of Philosophy and Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, PA (AJL).
Georgina FreemanStudies of Translation, Ethics and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montréal, QC, Canada (BC, ND, GF, AH, NM, SH, JK); University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada (TR); Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (SH); Department of Philosophy and Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, PA (AJL).
Amanda HakalaStudies of Translation, Ethics and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montréal, QC, Canada (BC, ND, GF, AH, NM, SH, JK); University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada (TR); Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (SH); Department of Philosophy and Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, PA (AJL).
Nathalie MacKinnonStudies of Translation, Ethics and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montréal, QC, Canada (BC, ND, GF, AH, NM, SH, JK); University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada (TR); Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (SH); Department of Philosophy and Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, PA (AJL).
Tim RamsayStudies of Translation, Ethics and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montréal, QC, Canada (BC, ND, GF, AH, NM, SH, JK); University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada (TR); Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (SH); Department of Philosophy and Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, PA (AJL).
Spencer HeyStudies of Translation, Ethics and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montréal, QC, Canada (BC, ND, GF, AH, NM, SH, JK); University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada (TR); Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (SH); Department of Philosophy and Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, PA (AJL).
Alex John LondonStudies of Translation, Ethics and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montréal, QC, Canada (BC, ND, GF, AH, NM, SH, JK); University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada (TR); Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (SH); Department of Philosophy and Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, PA (AJL).
Jonathan KimmelmanStudies of Translation, Ethics and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montréal, QC, Canada (BC, ND, GF, AH, NM, SH, JK); University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada (TR); Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (SH); Department of Philosophy and Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, PA (AJL). jonathan.kimmelman@mcgill.ca.

Funding

Canadian Institutes of Health Research EOG111391
6 · The paper itself

Abstract

backgroundLittle is known about the total patient burden associated with clinical development and where burdens fall most heavily during a drug development program. Our goal was to quantify the total patient burden/benefit in developing a new drug.

methodsWe measured risk using drug-related adverse events that were grade 3 or higher, benefit by objective response rate, and trial outcomes by whether studies met their primary endpoint with acceptable safety. The differences in risk (death rate) and benefit (overall response rate) between industry and nonindustry trials were analyzed with an inverse-variance weighted fixed effects meta-analysis implemented as a weighted regression analysis. All statistical tests were two-sided.

resultsWe identified 103 primary publications of sunitinib monotherapy, representing 9092 patients and 3991 patient-years of involvement over 10 years and 32 different malignancies. In total, 1052 patients receiving sunitinib monotherapy experienced objective tumor response (15.7% of intent-to-treat population, 95% confidence interval [CI] = 15.3% to 16.0%), 98 died from drug-related toxicities (1.08%, 95% CI = 1.02% to 1.14%), and at least 1245 experienced grade 3-4 drug-related toxicities (13.7%, 95% CI = 13.3% to 14.1%). Risk/benefit worsened as the development program matured, with several instances of replicated negative studies and almost no positive trials after the first responding malignancies were discovered.

conclusionsEven for a successful drug, the risk/benefit balance of trials was similar to phase I cancer trials in general. Sunitinib monotherapy development showed worsening risk/benefit, and the testing of new indications responded slowly to evidence that sunitinib monotherapy would not extend to new malignancies. Research decision-making should draw on evidence from whole research programs rather than a narrow band of studies in the same indication.

Indexed as

Angiogenesis InhibitorsAntineoplastic AgentsClinical Trials as TopicDrug ApprovalHumansIndolesNeoplasmsPyrrolesRisk AssessmentSunitinibUnited StatesUnited States Food and Drug AdministrationAngiogenesis InhibitorsAntineoplastic AgentsIndolesPyrrolesSunitinib

Identifiers

PMID26547927
PMCPMC5943825

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.