Background: Advances in medicine, clinical trial design, and statistical methods affect product approvals. Over the last decade, there were many breakthroughs in the development of novel cancer therapies, including the wide application of biomarkers in drug development. Understanding trends and patterns of trial design and data submissions that lead to the approval of these novel agents assists oncologists, investigators, and regulatory personnel. Methods: All new molecular entity (NME) therapeutic oncological agents approved for the first time within the past 13 years (January 1, 1999 to December 31, 2011) were analyzed for product features, approved indications, regulatory metrics, and clinical trial design. Patterns and trends were reviewed. July 2005 marked the midpoint of this review, concurrent with the FDA establishing the Office of Oncology Drug Products (OODP). Regulatory metrics before and after the establishment of the OODP were compared and analyzed. The Fisher exact test was applied for statistical analyses. Results: A total of 47 new oncological approvals were identified, 2 to 7 approvals per year (median, 3.0), with 6.0-month median reviews. Comparing the pre- and post-OODP period, there was trending towards more approvals (4.3/year vs 2.9/year) along with more targeted agent approvals (50% vs 21%) in the post-OODP period, although these metrics did not reach statistical significance due to relatively small numbers and large variances. There were also numerically fewer orphan designations (36% vs 53%) and accelerated approvals (32% vs 37%) in the post-OODP period. Approvals were for small molecule targeted agents, 38% (frequently kinase inhibitors); monoclonal antibodies, 17%; conventional cytotoxics, 28%; hormonal agents, 13%; and miscellaneous agents, 4%. Two 2011 approvals were associated with companion diagnostics. First-line indications accounted for only 36%; 62% were parenterally administered. Multinational, multicenter, randomized phase II or III trials utilizing overall survival or progression-free survival endpoints were common pivotal trial features in solid tumors. Hematological malignancy trials involved multiple small, single-arm phase II studies measuring mainly response rate, commonly resulting in accelerated approval. Placebo controls (19%) and blinding (24%) were both seldom employed. Conclusions: Over the last 13 years, 55% of NME approvals were targeted agents or monoclonal antibodies, most not for first-line use. Most applications relied upon a single pivotal study for approval. Randomized trials supported most solid tumor approvals, whereas single-arm phase II studies supported (mostly accelerated) approvals in hematological malignancies. After establishment of the OODP, there were trends towards more approvals and less orphan designations.
6016 Background: Current estimates are less than 5% of adult cancer patients participate in clinical trials. Initiatives to address barriers to accrual (such as age, physician bias, etc) are ongoing. However, with more drugs in the pipeline and more clinical trials being conducted, demand for trial participants may be outpacing the current “supply”. Methods: The ClinicalTrials.gov database, maintained by National Institutes of Health was selected for review on the basis that it is proposed to be the mandated repository for clinical trials information. Over a 2 month period, the database was mined for all active, US recruiting, phase I, I/II, II, and III trials in breast, lung, and prostate cancers. Results: There were 290 breast, 212 lung, and 177 prostate cancer trials with the prespecified criteria. The number of patients needed to complete these trials is 151,311 (breast), 33,498 (lung), and 53,181 (prostate). These represent 19.4% to 71.6% of the American Cancer Society incidence estimates of the studied tumors. NCI, industry, and academia sponsored, either solely or in collaborations, 42.1%, 26.5%, and 45.6% of trials, respectively. Majority of studies were phase II (51%), with 11.5% phase I, and 15.6% phase III. Remaining studies were either combined phase I/II studies or not specified. Significant percentage of trials involved pts with advanced/metastatic disease (54% breast, 51.4% lung, and 44.6% prostate). Conclusions: Although many studies have anticipated enrollment period over several years, the number of trial participants needed to complete these studies is quite daunting. Our results are likely under-estimates as not all studies currently enrolling patients may be included in this registry, and not all studies in the database specified the recruitment goal. Although not all trial participants are drawn from the incidence numbers, it is clear that given the current trial participation rate, demand has outpaced the supply. The medical community has the ethical responsibility to ensure sufficient patient enrollment for clinical trials. In addition to addressing accrual barriers, the authors encourage the establishment of a task force including academia, government, and industry to systematically evaluate and prioritize the types of trials being conducted. No significant financial relationships to disclose.
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