scholarly journals Response to letter: Wenle Zhao and Vance W. Berger, Better alternatives to permuted block randomization for clinical trials with unequal allocation

Hematology ◽  
2016 ◽  
Vol 22 (1) ◽  
pp. 64-64
Author(s):  
Will Meurer ◽  
Jeffrey Glassberg ◽  
Jason Connor
Keyword(s):  
Clinical Trials ◽  
Block Randomization ◽  
Unequal Allocation

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]

Quantification of Predictability in Clinical Trials Using Block Randomization

2004 ◽  
Vol 38 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Thérèse Dupin-Spriet ◽  
Jacques Fermanian ◽  
Alain Spriet
Keyword(s):  
Clinical Trials ◽  
Block Randomization

Influence of Selection Bias on the Test Decision

2012 ◽  
Vol 51 (02) ◽  
pp. 138-143 ◽  
Author(s):  
E. Cramer ◽  
L. N. Kennes ◽  
N. Heussen ◽  
M. Tamm
Keyword(s):  
Clinical Trials ◽  
Selection Bias ◽  
Error Rate ◽  
Randomized Clinical Trials ◽  
Type I Error ◽  
Patient Characteristics ◽  
Allocation Concealment ◽  
Type I ◽  
Type I Error Rate ◽  
Block Randomization

SummaryBackground: Selection bias arises in clinical trials by reason of selective assignment of patients to treatment groups. Even in randomized clinical trials with allocation concealment this phenomenon can occur if future assignments can be predicted due to knowledge of former allocations.Objectives: Considering unmasked randomized clinical trials with allocation concealment the impact of selection bias on type I error rate under permuted block randomization is investigated. We aimed to extend the existing research into this topic by including practical assumptions concerning misclassification of patient characteristics to get an estimate of type I error close to clinical routine. To establish an upper bound for the type I error rate different biasing strategies of the investigator are compared first. In addition, the aspect of patient availability is considered.Methods: To evaluate the influence of selection bias on type I error rate under several practical situations, different block sizes, selection effects, biasing strategies and success rates of patient classification were simulated using SAS.Results: Type I error rate exceeds 5 percent significance level; it reaches values up to 21 percent. More cautious biasing strategies and misclassification of patient characteristics may diminish but cannot eliminate selection bias. The number of screened patients is about three times larger than the needed number for the trial.Conclusions: Even in unmasked randomized clinical trials using permuted block randomization with allocation concealment the influence of selection bias must not be disregarded evaluating the test decision. It should be incorporated when designing and reporting a clinical trial.

scholarly journals Sequential boundaries approach in clinical trials with unequal allocation ratios

2006 ◽  
Vol 6 (1) ◽  
Author(s):  
Peyman Jafari ◽  
Seyyed Mohammad Taghi Ayatollahi ◽  
Javad Behboodian
Keyword(s):  
Clinical Trials ◽  
Unequal Allocation

Properties of permuted-block randomization in clinical trials

1988 ◽  
Vol 9 (4) ◽  
pp. 327-344 ◽  
Author(s):  
John P. Matts ◽  
John M. Lachin
Keyword(s):  
Clinical Trials ◽  
Block Randomization

An Alternative Proposal for “Mixed Randomization” by Schulz and Grimes

2005 ◽  
Vol 44 (04) ◽  
pp. 572-576 ◽  
Author(s):  
G. Kundt
Keyword(s):  
Clinical Trials ◽  
Block Size ◽  
Large Block ◽  
Case Scenario ◽  
Restricted Randomization ◽  
Worst Case ◽  
Equal Group ◽  
Randomization Scheme ◽  
Alternative Proposal ◽  
Block Randomization

Summary Objective: Randomization is an important part of clinical trials. Using permuted-block randomization for forcing equal group sizes potentially harms the unpredictability of treatment assignments. This can allow bias to creep into a trial. As an alternative, Schulz and Grimes suggest a “Mixed randomization” scheme which introduces more complexity to realize randomization. The objective of our research was to work out a model for randomization which is easier to handle than “Mixed randomization”, with an equal level of performance in unpredictability and balance. Methods: We analyzed a “Mixed randomization” procedure regarding the degree of unpredictability and balancing power and compared performance using permuted-block randomization with very large block size in a worst case scenario. Our work was done by the application of Blackwell-Hodges model for evaluation of the unpredictability of treatment assignments. Results: Regarding unpredictability, performance of permuted-block randomization with block size b = 36 was very similar to that of “Mixed randomization”. Regarding balancing power it was more favourable than “Mixed randomization”. Conclusion: Results of Schulz and Grimes are very important as they emphasized that mildly unequal sample sizes of therapy groups don’t cause problems. But the suggested scheme of “Mixed randomization” to a large extent adds complexity and we do not believe that this proposal is very feasible. Basically, we rather recommend the use of only one restricted randomization procedure in the best way. This can be permuted-block randomization with optimum choice of a large block size.

Localization of Gallium-67 in Peritoneal Cells by Electron Microscopic Autoradiography

1973 ◽  
Vol 31 ◽  
pp. 404-405
Author(s):  
D. C. Swartzendruber ◽  
Norma L. Idoyaga-Vargas
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Tumor Tissue ◽  
Soft Tissue Tumors ◽  
Clinical Usefulness ◽  
Electron Microscopic ◽  
Normal Cells ◽  
Electron Microscopic Autoradiography ◽  
Peritoneal Cells ◽  
Gallium 67

The radionuclide gallium-67 (67Ga) localizes preferentially but not specifically in many human and experimental soft-tissue tumors. Because of this localization, 67Ga is used in clinical trials to detect humar. cancers by external scintiscanning methods. However, the fact that 67Ga does not localize specifically in tumors requires for its eventual clinical usefulness a fuller understanding of the mechanisms that control its deposition in both malignant and normal cells. We have previously reported that 67Ga localizes in lysosomal-like bodies, notably, although not exclusively, in macrophages of the spocytaneous AKR thymoma. Further studies on the uptake of 67Ga by macrophages are needed to determine whether there are factors related to malignancy that might alter the localization of 67Ga in these cells and thus provide clues to discovering the mechanism of 67Ga localization in tumor tissue.

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