Quality of reporting of phase II trials in oncology in highly ranked oncology journals.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6582-6582
Author(s):  
Thomas Grellety ◽  
Aurelie Petit-Monéger ◽  
Abou Diallo ◽  
Simone Mathoulin-Pelissier ◽  
Antoine Italiano
Keyword(s):  
Sample Size ◽  
Phase Ii ◽  
Predictive Factors ◽  
Primary Endpoint ◽  
Phase Ii Trials ◽  
Quality Of Reporting ◽  
Score Analysis ◽  
Evaluable Population ◽  
Definition Of

6582 Background: Phase II trials represent an essential step in the development of anti-cancer drugs. The aim of this study was to assess the quality of their reporting in highly-ranked oncology journals, to investigate predictive factors of quality and to develop better reporting guidelines for authors. Methods: We reviewed the tables of contents of 8 peer-reviewed oncology journals published between January 2011 and December 2011 and with a 2011 impact factor (IF) >4: Br J Cancer, Eur J Cancer, Oncologist, J Clin Oncol, Lancet Oncol, JNCI, Clin Cancer Res and Ann Oncol. Two reviewers assessed the quality of each report by using a 44-point overall quality score (OQS; range, 0 to 44 points) inspired from the revised Consolidated Standards of Reporting Trials statement. Primary endpoint definition, justification of sample size and definition of the evaluable population for each endpoint, were assessed separately because of their crucial methodological importance using a 3-point key methodological score (KMS; range, 0 to 3). Exploratory analyses were used to identify predictive factors associated with the different scores. Results: 156 articles were included. Agreement between the reviewers for each item was good (kappa coefficient range: 0.62-1). The median OQS was 28 (range: 9-35). OQS sub-score analysis showed that reporting of statistical methods was particularly low with a mean of 2.5 (6 items). The median KMS was 2 (range 0-3). Primary endpoint definition, justification of sample size and definition of the evaluable population were reported only in 107 (68.6%), 121 (77.6%), and 52 (33.3%) cases, respectively. On multivariate analysis, reporting of clinicaltrial.gov registration was associated with improved OQS, OR = 3.2 (95CI, 1.5 to 7.1). No predictive factor for KMS were identified. Conclusions: Phases II trials reporting is still poor even in journals with strict editorial policies. This may lead to biased interpretation of phase II trial results. We have developed a checklist for use by authors, reviewers, and editors to improve reporting of these studies. As well as using a checklist during the preparation of their manuscript, we recommend that authors provide reviewers and readers with the last version of the study’s protocol.

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

PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0185536 ◽  
Author(s):  
Julien Langrand-Escure ◽  
Romain Rivoirard ◽  
Mathieu Oriol ◽  
Fabien Tinquaut ◽  
Chloé Rancoule ◽  
...  
Keyword(s):  
Systematic Review ◽  
Phase Ii ◽  
Phase Ii Trials ◽  
Quality Of Reporting

scholarly journals Quality of reporting of phase II trials: a focus on highly ranked oncology journals

2014 ◽  
Vol 25 (2) ◽  
pp. 536-541 ◽  
Author(s):  
T. Grellety ◽  
A. Petit-Monéger ◽  
A. Diallo ◽  
S. Mathoulin-Pelissier ◽  
A. Italiano
Keyword(s):  
Phase Ii ◽  
Phase Ii Trials ◽  
Quality Of Reporting

A Modification of Simon's Optimal Design for Phase II Trials When the Criterion Is Median Sample Size

1999 ◽  
Vol 20 (6) ◽  
pp. 555-566 ◽  
Author(s):  
John J. Hanfelt ◽  
Rebecca S. Slack ◽  
Edmund A. Gehan
Keyword(s):  
Optimal Design ◽  
Sample Size ◽  
Phase Ii ◽  
Phase Ii Trials

scholarly journals Beyond p-values: A phase II dual-criterion design with statistical significance and clinical relevance

2018 ◽  
Vol 15 (5) ◽  
pp. 452-461 ◽  
Author(s):  
Satrajit Roychoudhury ◽  
Nicolas Scheuer ◽  
Beat Neuenschwander
Keyword(s):  
Sample Size ◽  
Phase Ii ◽  
Clinical Relevance ◽  
Statistical Significance ◽  
Effect Estimate ◽  
Type I ◽  
Operating Characteristics ◽  
Phase Ii Trials ◽  
Standard Design ◽  
Standard Designs

Background Well-designed phase II trials must have acceptable error rates relative to a pre-specified success criterion, usually a statistically significant p-value. Such standard designs may not always suffice from a clinical perspective because clinical relevance may call for more. For example, proof-of-concept in phase II often requires not only statistical significance but also a sufficiently large effect estimate. Purpose We propose dual-criterion designs to complement statistical significance with clinical relevance, discuss their methodology, and illustrate their implementation in phase II. Methods Clinical relevance requires the effect estimate to pass a clinically motivated threshold (the decision value (DV)). In contrast to standard designs, the required effect estimate is an explicit design input, whereas study power is implicit. The sample size for a dual-criterion design needs careful considerations of the study’s operating characteristics (type I error, power). Results Dual-criterion designs are discussed for a randomized controlled and a single-arm phase II trial, including decision criteria, sample size calculations, decisions under various data scenarios, and operating characteristics. The designs facilitate GO/NO-GO decisions due to their complementary statistical–clinical criterion. Limitations While conceptually simple, implementing a dual-criterion design needs care. The clinical DV must be elicited carefully in collaboration with clinicians, and understanding similarities and differences to a standard design is crucial. Conclusion To improve evidence-based decision-making, a formal yet transparent quantitative framework is important. Dual-criterion designs offer an appealing statistical–clinical compromise, which may be preferable to standard designs if evidence against the null hypothesis alone does not suffice for an efficacy claim.

scholarly journals Randomized controlled trials and neurosurgery: the ideal fit or should alternative methodologies be considered?

2016 ◽  
Vol 124 (2) ◽  
pp. 558-568 ◽  
Author(s):  
Alireza Mansouri ◽  
Benjamin Cooper ◽  
Samuel M. Shin ◽  
Douglas Kondziolka
Keyword(s):  
Randomized Controlled Trials ◽  
Sample Size ◽  
English Language ◽  
Sample Size Calculation ◽  
Median Number ◽  
Controlled Trials ◽  
Quality Of Reporting ◽  
Randomized Controlled ◽  
Mesh Terms

OBJECT Randomized-controlled trials (RCTs) are advocated to provide high-level medical evidence. However, in neurosurgery, there are barriers to conducting RCTs. The authors of this study sought to analyze the quality of neurosurgical RCTs since 2000 to determine the adequacy of their design and reporting. METHODS A search of the MEDLINE and EMBASE databases (2000–2014) was conducted. The medical subject heading (MeSH) terms used in the search included: “neurosurgery” OR “neurosurgical procedure,” “brain neoplasms,” “infarction” and “decompression,” “carotid stenosis,” “cerebral hemorrhage,” and “spinal fusion.” These studies were limited to RCTs, in humans, and in the English language. The Consolidated Standards for Reporting of Trials (CONSORT) and Jadad scales were used to assess the quality of RCT design and reporting. The standardized median times cited (median citations divided by years since publication) were used to assess impact. A pragmatic-explanatory continuum indicator summary-based scale was used to assess the design of the studies as primarily pragmatic or explanatory. RESULTS Sixty-one articles were identified, and the following subspecialties were the most common: vascular (23, 37%), followed by functional neurosurgery and neurooncology (both 13, 21%). The following nations were the primary leaders in RCTs: US (25 studies, 41%), Germany (8 studies, 13%), and the United Kingdom (7 studies, 11%). Median sample size was 100 (interquartile range [IQR] 41.5–279). The majority of the studies (40, 66%) had pragmatic objectives. The median number of times cited overall was 69 (IQR 20.5–193). The combined median CONSORT score was 36 (IQR 27.5–39). Blinding was most deficiently reported. Other areas with a relatively low quality of reporting were sample size calculation (34.2% of surgical, 38.5% of drug, and 20% of device studies), allocation concealment (28.9% of surgical, 23.1% of drug, and 50% of device studies), and protocol implementation (18.4% of surgical, 23% of drug, and 20% of device studies). The quality of reporting did not correlate with the study impact. All studies had a median Jadad score ≤ 3. Thirty-three pragmatic studies (83%) and 5 explanatory studies (25%) met the design objectives. All pragmatic studies based on drug and device trials met their objectives, while 74% of pragmatic surgical trials met their objectives. CONCLUSIONS The prevalence of neurosurgical RCTs is low. The quality of RCT design and reporting in neurosurgery is also low. Many study designs are not compatible with stated objectives. Pragmatic studies were more likely to meet design objectives. Given the role of RCTs as one of the highest levels of evidence, it is critical to improve on their methodology and reporting.

Seamless phase II/III trial design with survival and PRO endpoints for treatment selection: Case study of RTOG 1216.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS6099-TPS6099
Author(s):  
David Ira Rosenthal ◽  
Qiang Zhang ◽  
Merrill S. Kies ◽  
Minh-Tam Truong ◽  
Richard Jordan ◽  
...  
Keyword(s):  
Sample Size ◽  
Phase Ii ◽  
Trial Design ◽  
Experimental Treatment ◽  
Phase Iii ◽  
Operating Characteristics ◽  
Phase Ii Trials ◽  
Trial Duration ◽  
Sequential Method ◽  
Common Control

TPS6099 Background: Clinical trial results from phase II trials to select an experimental treatment arm for separate phase III trial comparison can require years. Cancer clinical trials also now aim at both survival and PRO/functional outcomes, especially in head and neck (HN) studies. We developed a unique seamless phase II/III trial design to save on sample size and trial duration. The initial multi-arm phase II trial selects the most effective regimen among multiple experimental arms by first comparing each of the new treatments to a common control arm, using chosen endpoints, such as progression free survival. The winner will be tested for overall survival in the phase III study. Methods: We propose a phase II/III design to test the efficacy of experimental arms of postoperative radiation (RT) + docetaxel or RT + docetaxel + cetuximab in patients with HN squamous cancer. These are compared to the control arm of RT + cisplatin in the phase II part. Only one arm will be selected to go on to phase III depending on efficacy (PFS), PRO and safety outcomes. One experimental arm must be sufficiently better than the common control arm and the winner not having increased toxicity or functional cost to be selected for phase III inclusion. If not, the trial is halted for futility. Patients in the phase II selected arm and the control arm are included in phase III testing. Group sequential method is used to design each component. Separate interim efficacy and futility analyses are built in such that each endpoint can be monitored as in separate phase II, III trials. Once sample sizes are derived, operating characteristics for the seamless II/III design are evaluated through simulations under the null and various alternative hypotheses. Savings on sample size and time are compared to typical separate phase II and III designs and to the design testing only the arm of RT + docetaxel + cetuximab in phase II. Conclusion: The phase II/III RTOG 1216 HNC trial offers cost effectiveness, operational efficiency and scientific innovation.

The quality of reporting of phase II and III trials for new antipsychotics: a systematic review

2014 ◽  
Vol 45 (3) ◽  
pp. 467-479 ◽  
Author(s):  
M. X. Patel ◽  
S. Collins ◽  
J. Hellier ◽  
G. Bhatia ◽  
R. M. Murray
Keyword(s):  
Systematic Review ◽  
Phase Ii ◽  
Cost Utility ◽  
Quality Of Reporting ◽  
Quality Reporting ◽  
Primary Hypothesis ◽  
The Cost ◽  
Phase Ii And Iii ◽  
New Antipsychotics

BackgroundThe findings of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and the Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS) called previous trials of antipsychotics into question, including pre-licensing trials. Concerns regarding methodological robustness and quality of reporting increased. This systematic review aimed to examine the quality of reporting of phase II and III trials for new antipsychotics in the aftermath of the CATIE and CUtLASS studies.MethodElectronic searches were conducted in EMBASE, Medline and Cochrane databases and also ClinicalTrials.gov for antipsychotic trials (published between January 2006 and February 2012). Phase II and III randomized controlled trials (RCTs) for iloperidone, asenapine, paliperidone, olanzapine, lurasidone and pomaglumetad methionil were selected for schizophrenia and schizoaffective disorder. The reporting of the methodology was evaluated in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines.ResultsThirty-one articles regarding 32 studies were included. There was insufficient reporting of design in 47% of studies and only 13% explicitly stated a primary hypothesis. Exclusion criteria were poorly reported for diagnosis in 22% of studies. Detail regarding comparators, particularly placebos, was suboptimal for 56% of studies, and permitted concomitant medication was often not reported (19%). Randomization methods were poorly described in 56% of studies and reporting on blinding was insufficient in 84% of studies. Sample size calculations were insufficiently reported in 59% of studies.ConclusionsThe quality of reporting of phase II and III trials for new antipsychotics does not reach the standards outlined in the CONSORT guidelines. Authors often fail to adequately report design and methodological processes, potentially impeding the progress of research on antipsychotic efficacy. Both policymakers and clinicians require high quality reporting before decisions are made regarding licensing and prescribing of new antipsychotics.

Two-stage seamless transition design from open-label single-arm to randomized double-arm clinical trials

2016 ◽  
Vol 27 (1) ◽  
pp. 158-171 ◽  
Author(s):  
Haolun Shi ◽  
Guosheng Yin
Keyword(s):  
Clinical Trials ◽  
Sample Size ◽  
Phase Ii ◽  
Therapeutic Effects ◽  
Operating Characteristics ◽  
Phase Ii Trials ◽  
Open Label ◽  
Two Stage ◽  
Trade Offs ◽  
Experimental Drug

Conventional phase II clinical trials use either a single- or multi-arm comparison scheme to examine the therapeutic effects of the experimental drug. Both single- and multi-arm evaluations have their own merits; for example, single-arm phase II trials are easy to conduct and often require a smaller sample size, while multiarm trials are randomized and typically lead to a more objective comparison. To bridge the single- and double-arm schemes in one trial, we propose a two-stage design, in which the first stage takes a single-arm comparison of the experimental drug with the standard response rate (no concurrent treatment) and the second stage imposes a two-arm comparison by adding an active control arm. The design is calibrated using a new concept, the detectable treatment difference, to balance the trade-offs between futility termination, power, and sample size. We conduct extensive simulation studies to examine the operating characteristics of the proposed method and provide an illustrative example of our design.

scholarly journals Quality of reporting of pilot and feasibility cluster randomised trials: a systematic review

BMJ Open ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. e016970 ◽  
Author(s):  
Claire L Chan ◽  
Clémence Leyrat ◽  
Sandra M Eldridge
Keyword(s):  
Hypothesis Testing ◽  
Sample Size ◽  
Randomised Trials ◽  
Quality Of Reporting ◽  
Cluster Randomised Trials ◽  
Cluster Randomised ◽  
Pilot Trials ◽  
Formal Hypothesis Testing ◽  
Cluster Design

ObjectivesTo systematically review the quality of reporting of pilot and feasibility of cluster randomised trials (CRTs). In particular, to assess (1) the number of pilot CRTs conducted between 1 January 2011 and 31 December 2014, (2) whether objectives and methods are appropriate and (3) reporting quality.MethodsWe searched PubMed (2011–2014) for CRTs with ‘pilot’ or ‘feasibility’ in the title or abstract; that were assessing some element of feasibility and showing evidence the study was in preparation for a main effectiveness/efficacy trial. Quality assessment criteria were based on the Consolidated Standards of Reporting Trials (CONSORT) extensions for pilot trials and CRTs.ResultsEighteen pilot CRTs were identified. Forty-four per cent did not have feasibility as their primary objective, and many (50%) performed formal hypothesis testing for effectiveness/efficacy despite being underpowered. Most (83%) included ‘pilot’ or ‘feasibility’ in the title, and discussed implications for progression from the pilot to the future definitive trial (89%), but fewer reported reasons for the randomised pilot trial (39%), sample size rationale (44%) or progression criteria (17%). Most defined the cluster (100%), and number of clusters randomised (94%), but few reported how the cluster design affected sample size (17%), whether consent was sought from clusters (11%), or who enrolled clusters (17%).ConclusionsThat only 18 pilot CRTs were identified necessitates increased awareness of the importance of conducting and publishing pilot CRTs and improved reporting. Pilot CRTs should primarily be assessing feasibility, avoiding formal hypothesis testing for effectiveness/efficacy and reporting reasons for the pilot, sample size rationale and progression criteria, as well as enrolment of clusters, and how the cluster design affects design aspects. We recommend adherence to the CONSORT extensions for pilot trials and CRTs.

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