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

Abstract

Even 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.

Trials that say “maybe”: the disconnect between exploratory and confirmatory testing after drug approval

“…Of all monotherapy trials launched within five years of their US approval (n=132),78 we found 41 (31%) that met their primary efficacy endpoint with acceptable toxicity. Five of these trials were the basis of four recommendations for off-label use in clinical practice guidelines by the National Comprehensive Cancer Network (NCCN), an organisation whose guidelines in the US are used to set reimbursement policies.…”

“…But, for this system to work, early phase exploratory testing must be tightly coupled with late phase, confirmatory trials. Studies of clinical development78 indicate that drug companies and public funding agencies often generate prolonged clinical agnosticism, which can be sufficient to influence physicians and healthcare system decisions. Who could blame companies for not seeking to capitalise on this opportunity?…”

A Framework for Assessing Scientific Merit in Ethical Review of Clinical Research

“…A new approach to data visualization of research programs could be particularly informative here. For example, some recent analyses of drug development, involving interventions in cancer 33 and cardiovascular medicine, 34 have elucidated the potential research waste and harms to participants that may arise when many trials of new treatments are conducted in parallel with each other. These analyses employ a technique called “accumulating evidence and research organization” (“AERO”) graphing, which visually depicts the volume and patterns of research activity for a given scientific domain 35 …”

Nonpublication of trial results for new neurological drugs: A systematic review

“…35,36 Conclusion Despite their ethical and practical importance, results of trials of unlicensed drugs are heavily under-reported. First, longer follow-up might capture more publications.…”