A review of perspectives on the use of randomization in phase II oncology trials

Historically, phase II oncology trials assessed a treatment’s efficacy by examining its tumor response rate in a single-arm trial. Then, approximately 25 years ago, certain statistical and pharmacological considerations ignited a debate around whether randomized designs should be utilized instead. Here, based upon an extensive literature review, we review the arguments on either side of this debate. In particular, we describe the numerous factors that relate to the reliance of single-arm trials on historical control data, and detail the trial scenarios in which there was general agreement on preferential utilization of single-arm or randomized design frameworks, such as the use of single-arm designs when investigating treatments for rare cancers. We then summarize the latest figures on phase II oncology trial design, contrasting current design choices against historical recommendations on best practice. Ultimately, we find several ways in which the design of recently completed phase II trials does not appear to align with said recommendations. For example, despite advice to the contrary, only 66.2% of the assessed trials that employed progression-free survival as a primary or co-primary outcome used a randomized comparative design. In addition, we identify that just 28.2% of the considered randomized comparative trials came to a positive conclusion, as opposed to 72.7% of the single-arm trials. We conclude by describing a selection of important issues influencing contemporary design, framing this discourse in light of current trends in phase II, such as the increased use of biomarkers and recent interest in novel adaptive designs

La politique de subventionnement des compagnies théâtrales, une illustration du management de la complexité

Les théories de la complexité appliquées aux sciences de l'organisation permettent de dégager un certain nombre de recommandations en terme de management. Parallèlement, l'analyse du système de subventionnement des compagnies dramatiques indépendantes confirme l'inefficacité des modes de gestion normatifs dans des contextes où cohabitent des acteurs multilpes aux objectifs divergents, sinon contradictoires. Bien plus, il apparaît que les mécanismes par lesquels s'opère effectivement la régulation du système de subventionnement des compagnies théâtrales coïncident avec les préconisations du management de la complexité. Si cette convergence confirme la valeur descriptive et explicative des théories de la complexité, elle pose néanmoins question quant à leur pertinence prescriptive.Langrand-Escure Laure. La politique de subventionnement des compagnies théâtrales, une illustration du management de la complexité. In: Politiques et management public, vol. 14, n° 4, 1996. pp. 29-39

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review

<div><p>Background</p><p>Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal.</p><p><i>Objective</i> The present study aims at estimating the quality of reporting in published oncology phase II clinical trials.</p><p>Data sources</p><p>A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010–2015).</p><p>Study eligibility criteria</p><p>All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer.</p><p>Intervention</p><p>Quality of reporting was assessed using the Key Methodological Score.</p><p>Results</p><p>557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001).</p><p>Limitations</p><p><i>S</i>creening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate.</p><p>Conclusions & implications of key findings</p><p>This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles.</p></div

Outcome and Prognosis Factors of Stage IV Cervical Cancer Patients: A Decade Experience

International audiencePurpose/Objective(s)The aim of this study was to identify and compare prognostic factors, management strategies, and outcomes of very locally advanced cervical cancer (CC) (i.e., stages IVA) and metastatic CC (i.e., stages IV).Materials/MethodsA retrospective review was conducted, based on all consecutive patients treated for stage IV CC in a comprehensive cancer care center between 2004 and 2017.ResultsSixty-eight patients were included. Performance status (PS) was ≥ 2 for 35.9%. Median age at diagnosis was 60.5. There were 24 stage IVA CC (35.3%) and 44 stage IVB CC (64.7%). Seventeen patients with stage IVB CC had only para-aortic lymph nodes metastases (38.6%), 13 had only distant metastases (29.5%) and 14 had both (31.8%). Patients with stage IVA CC experienced a radiotherapy with curative intent (n=14, 58.3%) +/- a concomitant chemotherapy, or a palliative treatment (n=10, 41.7%). Twenty-three patients with stage IVB CC received a prior chemotherapy (52.3%), eleven a primary concomitant chemoradiation (25%), and ten a palliative treatment (22.7%). The mean follow-up was 18.0 months. The 5-year overall survival was 5.1% for stages IVA (95%CI=0.7-33.9), and 10.5% for stages IVB (95%CI=3.7-29.7). In multivariate analysis, PS>1 was identified as a poor prognostic factor of disease-specific survival for stage IVA CC. PS>1 and pelvic lymph nodes involvement were identified as poor prognostic factors of overall survival and disease-specific survival for stage IVB CC.ConclusionIn daily clinical practice, outcomes of stages IV CC are poor. Treatment of advanced and metastatic CC remains challenging. New management strategies are needed, as well as efficient preventive strategies

Factors associated with Key Methodological Score value: Multivariate analysis results.

<p>Factors associated with Key Methodological Score value: Multivariate analysis results.</p

Details of rate of reporting of each item of Key Methodological Score.

<p>Details of rate of reporting of each item of Key Methodological Score.</p