An Introduction to the Statistical Design of Phase III Cancer Clinical Trials

1997 ◽  
Vol 31 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Richard Sylvester
Keyword(s):  
Clinical Trials ◽  
Statistical Design ◽  
Phase Iii ◽  
Cancer Clinical Trials

Randomized Phase II Designs in Cancer Clinical Trials: Current Status and Future Directions

2005 ◽  
Vol 23 (19) ◽  
pp. 4450-4457 ◽  
Author(s):  
J. Jack Lee ◽  
Lei Feng
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Statistical Design ◽  
Stopping Rules ◽  
Phase Iii ◽  
Current Status ◽  
Cancer Clinical Trials ◽  
Future Directions ◽  
Randomized Phase Ii ◽  
Accrual Rate

Purpose Randomized phase II (RPh2) designs are popular in cancer clinical trials because of the smaller sample size requirements when multiple treatments are being evaluated. We reviewed the use of RPh2 designs and give comments on future directions. Design The trial design, statistical properties, conduct, data analysis, results, and reporting were examined in RPh2 trials reported from 1986 to 2002. Results A statistical design was reported in only 46% of the 266 cancer trials, and approximately half of those provided inadequate information. Most studies applied randomization to achieve patient comparability, while embedding a one-sample phase II design within each treatment arm. Seventy-five percent of the trials’ accruals were within ± 10% of their targets. The average accrual rate was 3.3 patients per month. Planned interim analyses were reported in 27% of the trials, and 56% of the trials were stopped early; 69%, 13%, 13%, and 4% of the trial discontinuations were because of lack of efficacy, efficacy, toxicity, and slow accrual, respectively. Thirty-nine trials (14%) recommended or started phase III evaluations, with four positive reports in six phase III studies identified. Conclusion There is a trend of increasing use of RPh2 designs in cancer research. Continued improvement in study design, conduct, analysis, and reporting is required to enhance the quality of RPh2 designs. The accrual rate and success rate of the trials remain low, and therefore, futility stopping rules to terminate ineffective treatment arm(s) should be implemented more frequently. More innovative, flexible RPh2 designs are needed to facilitate the development of effective cancer treatments.

scholarly journals Sponsor‐involved statistical analyses in Phase III cancer clinical trials

2020 ◽  
Vol 147 (12) ◽  
pp. 3579-3581
Author(s):  
Joseph Abi Jaoude ◽  
Ramez Kouzy ◽  
Bruce D. Minsky ◽  
Clifton David Fuller ◽  
Ying Yuan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Statistical Analyses ◽  
Phase Iii ◽  
Cancer Clinical Trials

Reducing patient eligibility criteria in cancer clinical trials.

1996 ◽  
Vol 14 (4) ◽  
pp. 1364-1370 ◽  
Author(s):  
S L George
Keyword(s):  
Clinical Trials ◽  
Sample Size ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Eligibility Criterion ◽  
Cancer Clinical Trials ◽  
Recent Trial ◽  
Eligibility Criteria ◽  
Eligibility Requirements

PURPOSE To discuss patient eligibility criteria in phase III cancer clinical trials in the larger setting of the complexity of these trials, to review the various reasons for imposing restrictive eligibility requirements, to discuss the problems caused by these requirements, to argue that these requirements should be greatly relaxed in most cancer clinical trials, to provide some guiding principles and practical suggestions to facilitate such a relaxation, and to give an example of how eligibility requirements were reduced in a recent clinical trial in acute lymphocytic leukemia. METHODS Implicit and explicit reasons for including eligibility criteria in clinical trials are reviewed. Safety concerns and sample size issues receive special attention. The types of problems restrictive eligibility criteria cause with respect to scientific interpretation, medical applicability, complexity, costs, and patient accrual are described. RESULTS A list of three items that each eligibility criterion should meet in order to be included is proposed and applied to a recent trial in acute lymphocytic leukemia. CONCLUSION Phase III clinical trials in cancer should have much broader eligibility criteria than the traditionally restrictive criteria commonly used. Adoption of less restrictive eligibility criteria for most studies would allow broader generalizations, better mimic medical practice, reduce complexity and costs, and permit more rapid accrual without compromising patient safety or requiring major increases in sample size.

Prevalence and characteristics of prematurely terminated cancer clinical trials.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6613-6613
Author(s):  
Kristian D Stensland ◽  
Asma Latif ◽  
Ryan Hendricks ◽  
Nitin Roper ◽  
Russell McBride ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Premature Termination ◽  
Disease Type ◽  
Phase Iii ◽  
Financial Resources ◽  
Cancer Clinical Trials ◽  
Enrollment Status ◽  
Substantial Investment ◽  
Early Closure ◽  
Study Sites

6613 Background: Cancer clinical trials require a substantial investment of patient and financial resources. Trials that are terminated prematurely contribute little to the scientific knowledge base and divert resources from answering other critical questions. To our knowledge, the prevalence of prematurely terminated trials, and reasons for termination, has not been comprehensively assessed. Methods: The ClinicalTrials.gov database was queried to identify all phase II and phase III interventional trials for any neoplasm registered between 9/2005 and 11/2012. The disease type, enrollment status, phase, funding source, and number of study sites were collected for each trial. A ”prematurely terminated” trial was any trial with a status of “terminated,” “withdrawn,” or “suspended.” The reason for termination was collected for each prematurely terminated trial. Results: We identified 11,483 interventional cancer trials, of which 1,326 (11.5%) were terminated prematurely. The reasons for termination are shown in the Table. The proportion of cancelled trials was similar among the various disease types, but was slightly higher in lung cancer (14.4% vs. 11.2%, p = 0.001), and slightly lower in skin cancer (8.2% vs. 11.7%, p = 0.022). The most common reason for premature termination was poor accrual (33.1%) though no reason was provided for 23% of trials. Trials sponsored by industry were more likely to be canceled than those with NIH or “other” sponsorship (13.4% vs. 9.9%, p = 0.001). Single center trials were more likely to be canceled than trials with multiple sites (13.6% vs. 9.4%, p < 0.001). Conclusions: More than one in ten cancer clinical trials is terminated prematurely. Full reporting of the reasons for premature termination is necessary for further evaluation of the cancer clinical trial enterprise and identification of predictors of study early closure. [Table: see text]

Analysis of racial distribution amongst patients in phase III cancer clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6588-6588 ◽  
Author(s):  
Swathi Gopishetty ◽  
Shruti Gupta ◽  
Vamsi Kota ◽  
Achuta Kumar Guddati
Keyword(s):  
Clinical Trials ◽  
Lymphoblastic Leukemia ◽  
Geographical Location ◽  
Racial Diversity ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Cancer Clinical Trials ◽  
Phase 3 ◽  
Asian Patients ◽  
Organ Specific

6588 Background: Minority races are often under-represented in cancer clinical trials as enrollment often occurs in large centers. Racial diversity may vary by geographical location and socio-economically backward areas may have a very different racial mix. This study explores the representation of different races in phase 3 clinical trials conducted in the past 10 years. Methods: Details about adult patients involved in phase 3 trials was extracted from the clinical trials.gov for 3 common solid organs and 3 hematological malignancies [breast, colon, lung, diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)]. The racial distribution of the patient population in these trials was analyzed. Results: African American and Asian patients are under-represented in all phase 3 cancer clinical trials. The table shows the average racial distribution in clinical trials for each organ specific malignancy. Conclusions: Most phase 3 clinical trials except for lung cancer, predominantly consisted of Caucasian patients. Applying the results of these trails to patients of other races should be done with caution. This study highlights the disparity of race in patients enrolled in clinical trials when compared to diverse and different populations that are encountered in practice. [Table: see text]

Trends in case-control allocation in phase III randomized cancer clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14582-e14582
Author(s):  
Shruti Gupta ◽  
Swathi Gopishetty ◽  
Srishti Malhotra ◽  
Vamsi Kota ◽  
Anand P. Jillella ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Trial Design ◽  
Phase Iii ◽  
Cancer Clinical Trials ◽  
Unequal Distribution ◽  
Equal Distribution ◽  
Advantages And Disadvantages ◽  
Significant Difference ◽  
And Control ◽  
Unequal Allocation

e14582 Background: Patients enrollment in cancer clinical trials has traditionally been limited to an equal distribution between cases and controls. Some clinical trials have an unequal distribution between the case and control arm. Although such unequal allocation is uncommon it has certain advantages and disadvantages to it. The trend and proportion of cancer clinical trials that have an unequal allocation has not been studied. Methods: Data about cancer clinical trials was extracted from clinical trials.gov. The query included phase 3 trials which included adults and were conducted between 2010 to 2017. Only clinical trials that were either completed or active – but not recruiting were included. T test was used to determine statistical difference between different subgroups. Results: 601 clinical trials were identified of which 356 trials with two arms and 47 trials with 3+ arms were identified. Amongst the eligible 298 trials with two arms, there were 216 trials with equal allocation (1:1) and 82 trials with unequal allocation. Amongst the eligible 29 trials with 3+ arms; there were 21 trials with equal allocation (1:1:1) and 8 trials with unequal allocation. There was no significant difference in the proportion of trials with unequal allocation over the time period from 2010 to 2017. The categories of cancer which had the highest number of two arm clinical trials with unequal allotment were: genitourinary, breast and hematological malignancies (Table). Conclusions: Cancer clinical trials with unequal allocation between case and control arms have been common in the past decade. This may represent a new trend in clinical trial design to help enhance closer monitoring of adverse events despite higher costs attached to this method.[Table: see text]

Professional medical writing assistance in oncology clinical trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14088-e14088
Author(s):  
Joseph Abi Jaoude ◽  
Ramez Kouzy ◽  
Walker Mainwaring ◽  
Timothy Lin ◽  
Austin B. Miller ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Scientific Communication ◽  
Phase Iii ◽  
Professional Writing ◽  
Academic Publishing ◽  
Cancer Clinical Trials ◽  
Fda Approval ◽  
English Speaking ◽  
Medical Writers

e14088 Background: Academic publishing remains the cornerstone of biomedical research and scientific communication. Researchers often assign professional medical writers (PMWs) to craft publications, as these individuals may improve the overall writing quality and/or reduce time to publication. We sought to characterize the landscape of PMW utilization in phase III cancer clinical trials. Methods: We searched ClinicalTrials.gov for phase III randomized clinical trials between the years 2003 and 2018. Randomized multi-arm trials assessing a therapeutic intervention in cancer patients were included. After identifying the corresponding publications, we identified whether a PMW was involved in writing the manuscript based on author disclosures, along with any related funding information. Results: Six-hundred oncology RCTs with corresponding manuscripts were identified. In total, 260 (43.3%) trials used a PMW. Financial support to medical writers was largely provided by the industry (247/260, 95.0%). In multivariate analyses, PMW utilization was higher among industry-funded trials compared to non-industry-funded trials (OR: 14.2, p= 0.001). PMWs were used more frequently to report successful trials that met their primary endpoint (OR: 1.8, p= 0.03) but did not differ between English-speaking and non-English-speaking countries ( p= 0.19). Cooperative group trials used PMWs with less frequency compared to non-cooperative groups (OR 0.68, p < 0.001). PMWs were used more often in trials that led to subsequent drug FDA approval (69.6% vs 40.6% in trials that did not lead to subsequent FDA approval), but this association did not reach statistical significance in multivariate analysis ( p = 0.744). The use of PMWs has increased significantly over time (OR: 1.11/year, p =0.001). Conclusions: In this analysis, we show a strikingly high prevalence of PMW utilization in phase III oncology trials, with a vast majority of industry-supported studies using PMWs. We believe that professional writing assistance plays an important role in clear and efficient scientific communication. However, the disproportionate role of PMWs in reporting positive, industry-funded trials may represent a conflict of interest. We urge continued and increased reporting of utilization and funding of professional writing assistance in cancer clinical trials.

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