DOI: 10.5061/dryad.zw3r22851
title: Patient burden and clinical advances associated with post-approval monotherapy cancer drug trials: a systematic review

description: Objectives: After regulatory approval, drug companies, public funding
 agencies and academic researchers often pursue trials aimed at extending
 the uses of a new drug by testing it in new non-approved indications.
 Patient burden and clinical impact of such research is not well
 understood. Design/setting: We conducted a retrospective cohort study of
 post-approval clinical trials launched within five years after the
 drug's first approval, testing anticancer drugs in monotherapy in
 indications that were first pursued after a drug's first FDA license,
 for all 12 anticancer drugs approved 2005-2007. (Search date: 2019-02-12.)
 Primary and secondary outcome measures: Our primary objective was to
 measure burden and clinical impact for patients enrolling in these trials.
 Each trial was sorted into a “trajectory” defined by the drug and cancer
 indication. Risk was operationalized by proportions of grade 3-4 severe
 adverse events and deaths. Clinical impact was measured by estimating the
 proportion of patients participating in trajectories that resulted in FDA
 approval, uptake into National Comprehensive Cancer Network (NCCN)
 clinical practice guidelines or advancement to randomized controlled
 trials (RCT) within eight years. Results: Our search captured 104
 published trials exploring monotherapy, including 69 unique trajectories.
 In total, trials in our sample enrolled 4699 patients. Grade 3-4 adverse
 events were experienced by 19.6% of patients; grade 5 events were
 experienced by 2.8% of patients. None of the trajectories launched after
 initial drug approval received FDA approval. Five trajectories were
 recommended by the NCCN within eight years of the first trial within that
 trajectory. Eleven trajectories were advanced to randomized controlled
 testing. Conclusions: The challenges associated with unlocking new
 applications for drugs that first received approval 2005-2007 were similar
 to those for developing new drugs altogether. Our findings can help inform
 priority setting in research, and provide a basis for calibrating
 expectations when considering enrollment in label-extending trials
description: Monotherapy clinical
 trials aimed at extending the label of the 12 novel anti-cancer drugs that
 received first FDA approval between 2005 and 2007 inclusive.
description: <strong>Trials.csv</strong> This
 CSV includes the per-trial data set, where every row describes one
 distinct clinical trial.   Column
 definitions: g34: Grade 3-4 adverse events
 g5: Grade 5 adverse events total_n: Total
 patient enrolment toxicity: Author-reported evaluation
 of toxicity primary: Primary endpoint
 attainment sponsor: Grouped into: industry; some/all
 non-industry; not stated date_of_enrolment and
 date_of_closure: Refers to trial enrolment period
 solid_or_not: Is the indication in question a solid or non-solid
 tumour?  
 <strong>Trajectories.csv</strong>
 This CSV describes the same set of trials as Trials.csv, but with
 data grouped into "trajectories" defined by the drug and
 indication being studied. Each row represents one such
 trajectory.   Column
 definitions: solid_or_not: Is the indication in
 question a solid or non-solid tumour? patients: Total
 number of patients in the trajectory Trials: Number of
 trials in the trajectory Approved: Whether the drug was
 approved for that indication by the FDA within our follow-up
 timeframe Reccomendation: Whether the drug was
 recommended for that indication explicitly by the NCCN within our
 follow-up timeframe Indication number: The number of
 the indication explored within that drug's development (e.g. the
 first indication explored in that drug's development would be given a
 1) first_enrol: The enrolment date of the first trial
 in this trajectory industry_trials: The number of
 trials sponsored by industry non_industry_trials: The
 number of trials sponsored by all or some non-industry sources
 ns_sponsor: Sponsor not stated highest_phase:
 The number of the trial with the highest phase in this
 trajectory k_positive_trials: The number of trials
 within this trajectory that had a positive primary outcome
 g34: Grade 3-4 adverse events g5: Grade 5
 adverse events g35: Grade 3-5 adverse events
 rct_w_survival: The date of enrolment for an RCT with a survival
 endpoint in the same trajectory registered on ClinicalTrials.gov, if it
 exists, NA otherwise nccn_uptake: The date of the NCCN
 recommendation, if any, NA otherwise