scholarly journals Time from Diagnosis to Initiation of Treatment of DLBCL and Implication for Potential Selection Bias in Clinical Trials

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3034-3034 ◽  
Author(s):  
Matthew J Maurer ◽  
Brian K Link ◽  
Thomas M. Habermann ◽  
Carrie A. Thompson ◽  
Cristine Allmer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Event Rate ◽  
Aggressive Disease ◽  
Time To Initiation ◽  
Initiation Of Therapy ◽  
Central Pathology ◽  
Delayed Time ◽  
Pathology Review

Abstract Background: There are a number of ongoing clinical trials assessing next-generation immunochemotherapy (IC) regimens (i.e. RX-CHOP) in DLBCL. In addition to standard clinical trial workup, some trials require central pathology review and/or molecular phenotyping before treatment assignment and/or initiation of therapy. There is concern that these studies may be biasing patient selection due to missing patients with aggressive disease who require immediate therapy and cannot delay their treatment to enroll on a study. Here we examine clinical characteristics and outcome stratified by the time from diagnosis to initiation of therapy from a large observational cohort of patients with DLBCL from the R-CHOP era. Methods: Patients were prospectively enrolled in the University of Iowa / Mayo Clinic SPORE Molecular Epidemiology Resource (MER) within 9 months of diagnosis and followed for relapse, retreatment, and death. Clinical management at diagnosis and subsequent therapies were per treating physician. This analysis includes patients with stage II-IV DLBCL or primary mediastinal B-cell lymphoma (PMBCL) who underwent front-line anthracycline based IC; patients with primary CNS lymphoma, PTLD, or a component of low-grade lymphoma were excluded. Time from diagnosis to treatment was defined as the time from date of first lymphoma-containing biopsy to the initiation of IC therapy; delayed therapy was defined as initiating therapy more than 14 days after diagnosis. Event-free survival was defined as time from diagnosis until progression, retreatment, or death due to any cause. EFS24 was defined as progression free status 24 months from diagnosis. Results: 720 patients with stage II-IV newly diagnosed DLBCL or PMBCL and treated with IC were enrolled in the MER from 2002-2012. Median age at diagnosis was 62 years (range 18-92) and 399 patients (55%) were male. 541 patients (75%) had stage III/IV disease and IPI at diagnosis was 0-1 in 166 patients (23%), 2 in 221 patients (31%), 3 in 222 patients (31%) and 4-5 in 111 patients (15%). 233 of 395 patients (59%) were GCB per Hans. At a median follow-up of 73 months, (range 0-163), 349 (49%) patients had an event and 267 patients died (37%); 37% of patients failed to achieve EFS24. Median time from initial lymphoma diagnosis to initiation of IC was 14 days (range 0-79, IQR=8-23). Patients with delay in therapy (>14 days from diagnosis) were more frequently female (50%, p=0.0051) and older than patients who initiated therapy within 14 days from diagnosis (median age at diagnosis of 63 years vs. 60 years, p=0.0008). Patients with delay in treatment initiation had universally less aggressive disease characteristics, including earlier stage, non-elevated LDH, 0-1 extranodal sites, absence of B-symptoms, lower ECOG PS, and lower IPI (see table). In addition, patients with delayed therapy were enriched for GCB subtype per Hans algorithm (p=0.056). Patients with initiation of therapy within 14 day of diagnosis had significantly worse outcome (EFS24 failure=44%) compared to patients with delayed time to initiation of therapy (EFS24 failure=28%, p<0.0001, figure), which remained significant after adjusting for either IPI or aaIPI (both p<0.005). The association between delayed time to initiation of therapy and EFS24 was observed in both GCB (EFS24 failure = 42% vs. 27%, p=0.019) and non-GCB (EFS24 failure = 46% vs. 27%, p=0.014) subsets by Hans. The lower event rate in delayed therapy patients results in an approximately 10% loss of power if the study was powered based on all patients regardless of timing from diagnosis to therapy. Conclusions: Patients with delayed therapy from diagnosis have less aggressive clinical characteristics compared to patients who initiate treatment within 14 days from diagnosis. Studies with a lengthy trial work-up including central pathology review period may be selecting patients with less aggressive disease based on the patient's ability to delay treatment to complete study enrollment requirements. Furthermore, selection of patients with less aggressive disease may result in underpowered studies due to a lower event rate (fewer events) than expected. This retrospective analysis would suggest that trials in DLBCL should consider streamlined enrollment and therapy initiation to avoid potential selection bias and loss of power. Further assessment of implications on trial design and outcomes by cell of origin in this setting is ongoing. Table Table. Figure Figure. Disclosures Maurer: Kite Pharma: Research Funding; Celgene: Research Funding. Ansell:BMS, Seattle Genetics, Merck, Celldex and Affimed: Research Funding. Nowakowski:Morphosys: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Research Funding.

scholarly journals Short Time between Progression after Immunochemotherapy and Initiation of Salvage Therapy (PTI) Is Associated with Inferior Long-Term Outcomes in Patients with Relapsed/Refractory DLBCL

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4204-4204 ◽  
Author(s):  
Matthew J. Maurer ◽  
Umar Farooq ◽  
Madison M Wahlen ◽  
Thomas M. Habermann ◽  
Gita Thanarajasingam ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Selection Bias ◽  
Salvage Therapy ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Aggressive Disease ◽  
Treatment Interval ◽  
Biopsy Confirmation

Abstract Background An association has been identified between the diagnosis-to-treatment interval (DTI) and prognostic clinical factors and outcomes in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (Maurer et al, JCO 2018). This association can result in inadvertent selection bias in clinical trials to exclude patients with aggressive disease due to the inability to delay treatment long enough to fulfill enrollment criteria, compromising the validity of clinical trial study results to the general population. A similar concern exists in the relapsed/refractory (r/r) DLBCL setting regarding patient selection bias against patients with aggressive disease requiring immediate treatment following relapse or progression. Here we examine the time from progression after immunochemotherapy (IC) to the initiation of first salvage chemotherapy and its association with outcome. Patients and Methods: Newly diagnosed patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER), now a subcohort of the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study, and followed for progression/relapse, retreatment, and death. This analysis includes patients with their first r/r DLBCL following frontline IC who initiated aggressive salvage chemotherapy as identified and included in a previous publication (Farooq et al, BJH 2017). The progression-to-treatment interval (PTI) was defined as the time in days from date of progression from IC to initiation of salvage therapy. The date of progression was defined as either a) the date biopsy was obtained for patients who had a biopsy to confirm progressive disease or b) the date of the scan or clinical examination indicating progression in patients who did not have a biopsy performed. Event-free survival (EFS) was defined as time from initiation of first salvage therapy to progression or relapse, initiation of new anti-lymphoma therapy, or death due to any cause; overall survival (OS) was defined as time from initiation of salvage therapy until death due to any cause. Results: 162 patients with r/r DLBCL enrolled in the MER from 2002-2012 who initiated aggressive salvage chemotherapy with intent to transplant and had confirmed dates for both progression after IC and start of salvage therapy were evaluated. Median age at first progression for these patients was 64 years (range 36-76) and 104 (64%) were male. Median time from diagnosis to first progression on IC was 6.7 months (IQR: 4.6-12.7). Initial salvage therapy was R-ICE (80%), R-DHAP (8%), rituximab, oxaliplatin, cytosine arabinoside, and dexamethasone (ROAD) (6%), and other (7%). At a median follow-up of 49 months from initiation of salvage therapy (IQR: 33-74), 116 patients had died (72%). Median PTI was 6 days (IQR: 2-13). 110 patients (68%) had biopsy confirmation of disease prior to initiating salvage therapy; median PTI was 2 days (IQR: 1-7) for patients who had biopsy confirmation vs. 7 days (IQR: 3-16) in patients without biopsy confirmation, Wilcoxon p=<0.0001. There was no difference in OS from initial salvage therapy between patients who did not have biopsy confirmation (HR=1.09, 95% CI: 0.74-1.60, p=0.68) compared to patients with biopsy confirmation. Patients with short PTI (0-6 days) had significantly worse overall survival from initiation of salvage therapy (median OS = 7.6 months, HR=2.10 (95% CI: 1.43-3.08) compared to patients who initiated therapy 7 or more days from progression (median OS = 29.7 months), logrank p<0.0001. This association remained consistent (HR=2.20, 95% CI: 1.48-3.26, p<0.0001) after adjusting for age and biopsy confirmation of progression. Short PTI was also associated with inferior response rate to initial salvage therapy (51% vs. 65%, p=0.058), lower rate of proceeding to transplant after initial salvage therapy (33% vs. 55%, p=0.0063), lower rate of being event-free 24 months from initial salvage therapy (16% vs 33%, p=0.011) and lower rate of ever proceeding to transplant (44% vs. 59%, p=0.057). Conclusions: A short progression-to-treatment interval is strongly associated with inability to proceed to transplant and inferior overall survival in r/r DLBCL. These results have implications for the design and interpretation of clinical trials in the relapsed/refractory setting. Figure. Figure. Disclosures Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Ansell:Trillium: Research Funding; Merck & Co: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Pfizer: Research Funding; Celldex: Research Funding; Takeda: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cerhan:Nanostring: Research Funding; Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board.

scholarly journals Nationwide incidence of sarcomas and connective tissue tumors of intermediate malignancy over four years using an expert pathology review network

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246958
Author(s):  
Gonzague de Pinieux ◽  
Marie Karanian ◽  
Francois Le Loarer ◽  
Sophie Le Guellec ◽  
Sylvie Chabaud ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Characteristics ◽  
Who Classification ◽  
Phase Iii ◽  
Histological Subtypes ◽  
Phase Ii Clinical Trials ◽  
Yearly Incidence ◽  
Independent Review ◽  
Low Incidence ◽  
Pathology Review

Background Since 2010, nationwide networks of reference centers for sarcomas (RREPS/NETSARC/RESOS) collected and prospectively reviewed all cases of sarcomas and connective tumors of intermediate malignancy (TIM) in France. Methods The nationwide incidence of sarcoma or TIM (2013–2016) was measured using the 2013 WHO classification and confirmed by a second independent review by expert pathologists. Simple clinical characteristics, yearly variations and correlation of incidence with published clinical trials are presented and analyzed. Results Over 150 different histological subtypes are reported from the 25172 patients with sarcomas (n = 18712, 74,3%) or TIM (n = 6460, 25.7%), with n = 5838, n = 6153, n = 6654, and n = 6527 yearly cases from 2013 to 2016. Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 70.7 and 24.4 respectively, with a combined incidence of 95.1/106/year, higher than previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors. Only GIST, as a single entity had a yearly incidence above 10/106/year. There were respectively 30, 64 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1–0.1/106, or < 0.1/106/year respectively. The 2 latter incidence groups represented 21% of the patients with 130 histotypes. Published phase III and phase II clinical trials (p<10−6) are significantly higher with sarcomas subtypes with an incidence above 1/106 per. Conclusions This nationwide registry of sarcoma patients, with exhaustive histology review by sarcoma experts, shows that the incidence of sarcoma and TIM is higher than reported, and that tumors with a very low incidence (1<106/year) are less likely to be included in clinical trials.

Characteristics of Patients with Chronic Myelogenous Leukemia in Chronic Phase Switched to Nilotinib or Dasatinib As Second-Line Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4447-4447
Author(s):  
Alexander R. Macalalad ◽  
Lei Chen ◽  
Annie Guerin ◽  
Jiayuan Luo ◽  
Eric Qiong Wu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chronic Myelogenous Leukemia ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Chronic Phase ◽  
Patient Characteristics ◽  
Myelogenous Leukemia ◽  
Imatinib Resistance ◽  
Analysis Group ◽  
Line Therapy

Abstract Abstract 4447 Background: Since 2007, nilotinib and dasatinib have been available for 2nd-line therapy for patients with chronic myelogenous leukemia in chronic phase (CML-CP) who are resistant or intolerant to imatinib. In clinical trials, both drugs have been shown to be effective and safe, but with different side-effect profiles. Currently, little is known about the characteristics of patients who are switched to nilotinib or dasatinib in a real-world setting. Methods: Through an online chart abstraction form, participating community physicians retrospectively submitted de-identified information on CML-CP patients ≥ 18 years old who switched after 10/28/2007 from imatinib to either 2nd-line nilotinib or dasatinib and who had at least 30 days of follow-up. When multiple patients met the selection criteria, up to 8 patients from each group were selected randomly by physicians. Patients enrolled in clinical trials or with concurrent malignancies were excluded. Information on patient characteristics at the time of switching TKI therapy was collected, including age, sex, race, comorbidities, prior imatinib dosing, reasons for switching, and the dose regimen of nilotinib or dasatinib at initiation. Characteristics were compared between nilotinib and dasatinib patients using Wilcoxon and chi-square tests. Results: 122 hematologists and oncologists provided information on 597 patients (301 on 2nd-line nilotinib and 296 on 2nd-line dasatinib). The table below summarizes the comparisons of the two groups. Both groups had similar age, sex, race, and comorbidity profile. Nilotinib patients were more likely than dasatinib patients to have had secondary imatinib resistance (p=0.047), more likely to have received a maximum imatinib dosing of 600 or 800 mg/day (p=0.006), and less likely to have switched due to imatinib intolerance (p=0.024). Conclusions: Patients switched to nilotinib vs. dasatinib had similar demographic and clinical characteristics at the time of switch, but nilotinib patients were more likely to have had an imatinib dose increase before the switch, and were more likely to have had secondary imatinib resistance. Patients switched to nilotinib vs. dasatinib were also less likely to have had imatinib intolerance. These findings suggest that resistance or intolerance to imatinib therapy have had more impact than patient demographics or clinical characteristics in deciding which drug to use for 2nd-line therapy. Disclosures: Macalalad: Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Luo:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Griffin:Novartis: Consultancy, Research Funding.

scholarly journals Targeted Sequencing of 7 Genes Can Help Reduce Pathologic Misclassification of MDS

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-33
Author(s):  
Johannes B Goll ◽  
Travis L Jensen ◽  
R. Coleman Lindsley ◽  
Rafael Bejar ◽  
Jason Walker ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Board Of Directors ◽  
Predictive Value ◽  
Research Funding ◽  
Targeted Sequencing ◽  
Advisory Committees ◽  
Test Set ◽  
Oncology Research ◽  
Central Pathology ◽  
Pathology Review

Introduction: The NHLBI National MDS Study (NCT02775383) is a prospective cohort study conducted at 92 community hospitals and 29 academic centers. It enrolls patients undergoing work up for suspected MDS to understand the genetic, epigenetic, and biological factors associated with the initiation and progression of the disease. Previously untreated, cytopenic participants undergo both local and centralized pathology review and are assigned a diagnosis, including MDS, MDS/MPN, AML with blasts &lt; 30%, and "Other". Emerging data suggests that Next Generation Sequencing (NGS), along with cytogenetics and clinical variables, may improve MDS diagnostic precision. Given that our study relies on central review (with additional tertiary pathology review used to adjudicate disagreements), we examined whether targeted gene sequencing data could be used to increase the agreement between local and central pathologic diagnosis of MDS vs. Other. Methods: Peripheral blood and bone marrow (BM) biopsy specimens from cytopenic patients, along with clinical history, CBC, and other results including karyotyping, FISH and pathology reports from local pathologists were reviewed by central pathologists. The updated 2016 WHO classifications were used to diagnose MDS. Targeted exon sequencing of 96 genes was performed using BM specimens. A subset of 648 individuals that were classified as MDS (n=212) or Other (n=436, including 90 CCUS and 89 individuals with other cancers) by pathology assessments were selected. A mean coverage of 1,317X was achieved and variants had a minimum variant allele frequency (VAF) of 2% (except FLT3). Variants for 596 subjects were manually reviewed to retain likely disease-causing variants to build a binary classifier (MDS vs. Other) using the maximum VAF per gene as input (Figure 1). Subjects diagnosed with MDS or Other by both central and local pathology were used for training, validation, and testing, and were considered "gold standard" (GS) cases (n=546). These subjects were split into 4 random groups with equal proportions of MDS cases. 75% of the GS cases were used to train and validate lasso-regularized logistic regression models using 3-fold cross validation. ROC curve analysis was carried out using the remaining 25% of GS cases (Test Set 1) on the best model to identify an optimal probability cut off point for classifying subjects as MDS. Model performance was then tested on 50 subjects for which the central and local pathology diagnosis disagreed (Test Set 2), as well as on 52 additional subjects irrespective of agreement (Test Set 3). Results : The best performing logistic regression model retained 7 genes as most informative in a discriminating diagnosis of MDS from Other based on their VAFs, in order of impact: TP53, SF3B1, U2AF1, ASXL1, TET2,STAG2, and SRSF2. We used this model to assign probabilities for each of the subjects in Test Set 1 and to estimate the performance using ROC analysis (Figure 1), resulting in a high area under the curve (AUC) of 0.89. We chose a probability cut-off of ≥0.17, being associated with a high percentage of correct classification of MDS with a sensitivity and specificity of 0.90 and 0.81, respectively. Among the cohort of 50 subjects with a discordant local and central pathology diagnosis (Test Set 2), the classifier accurately reassigned 37 subjects (accuracy = 74%) from the local to the central pathology. The blinded tertiary pathology reviewer agreed with central in all Test Set 2 cases. This included 24/34 MDS cases that had been labeled as Other by local pathology (positive predictive value [PPV]=0.89). 3/16 final pathology-classified Other cases were mis-classified as MDS by the local pathologist (negative predictive value [NPV] = 0.57). Next, we assessed the ability of the model to predict MDS vs. Other for 52 additional independent subjects using the third pathologist's diagnosis to break any ties (Test Set 3). The classifier correctly predicted 15/21 MDS cases (PPV=0.83) and misclassified 6/31 Others as MDS (NPV=0.82). The overall accuracy was 83%. Conclusions: We identified that VAFs for 7 genes can correctly re-classify subjects as either MDS or Other in 74% of cases that were misclassified between local and central pathology review. Further assessment on an independent cohort showed an accuracy of 83% of the model. Taken together, these data suggest that complementing pathology reviews with targeted sequencing of 7 genes could improve MDS diagnosis. Disclosures Lindsley: MedImmune: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Bluebird Bio: Consultancy; Takeda Pharmaceuticals: Consultancy. Bejar:Aptose Biosciences: Current Employment; AbbVie/Genentech: Honoraria; Astex/Otsuka: Honoraria; Takeda: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Forty-Seven/Gilead: Honoraria; Genoptix/NeoGenomics: Honoraria. DeZern:MEI: Consultancy; Astex: Research Funding; Abbvie: Consultancy; Celgene: Consultancy, Honoraria. Foran:H3Biosciences: Research Funding; Aptose: Research Funding; Kura Oncology: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Revolution Medicine: Consultancy; Xencor: Research Funding; Agios: Honoraria, Research Funding; Aprea: Research Funding; Actinium: Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding. Gore:Abbvie: Consultancy, Honoraria, Research Funding. Komrokji:Acceleron: Honoraria; Incyte: Honoraria; Abbvie: Honoraria; Agios: Speakers Bureau; BMS: Honoraria, Speakers Bureau; Jazz: Honoraria, Speakers Bureau; Geron: Honoraria; Novartis: Honoraria. Maciejewski:Alexion, BMS: Speakers Bureau; Novartis, Roche: Consultancy, Honoraria. Padron:Novartis: Honoraria; BMS: Research Funding; Incyte: Research Funding; Kura: Research Funding. Starczynowski:Captor Therapeutics: Consultancy; Tolero Therapeutics: Research Funding; Kurome Therapeutics: Consultancy, Current equity holder in private company, Research Funding. Sekeres:BMS: Consultancy; Takeda/Millenium: Consultancy; Pfizer: Consultancy.

scholarly journals Central Pathology Review for Phase III Clinical Trials: The Enabling Effect of Virtual Microscopy

2013 ◽  
Vol 137 (4) ◽  
pp. 492-495 ◽  
Author(s):  
Pawel Mroz ◽  
Anil V. Parwani ◽  
Piotr Kulesza
Keyword(s):  
Clinical Trials ◽  
Control Measure ◽  
Substantial Reduction ◽  
Virtual Microscopy ◽  
Turnaround Time ◽  
Phase Iii ◽  
Advantages And Disadvantages ◽  
Number Of Patients ◽  
Central Pathology ◽  
Pathology Review

Context.—Central pathology review (CPR) was initially designed as a quality control measure. The potential of CPR in clinical trials was recognized as early as in the 1960s and quickly became embedded as an integral part of many clinical trials since. Objective.—To review the current experience with CPR in clinical trials, to summarize current developments in virtual microscopy, and to discuss the potential advantages and disadvantages of this technology in the context of CPR. Data Sources.—A PubMed (US National Library of Medicine) search for published studies was conducted, and the relevant articles were reviewed, accompanied by the authors' experience at their practicing institution. Conclusions.—The review of the available literature strongly suggests the growing importance of CPR both in the clinical trial setting as well as in second opinion cases. However, the currently applied approach significantly impedes efficient transfer of slides and patient data. Recent advances in imaging, digital microscopy, and Internet technologies suggest that the CPR process may be dramatically streamlined in the foreseeable future to allow for better diagnosis and quality assurance than ever before. In particular, whole slide imaging may play an important role in this process and result in a substantial reduction of the overall turnaround time required for slide review at the central location. Above all, this new approach may benefit the large clinical trials organized by oncology cooperative groups, since most of those trials involve complicated logistics owing to enrollment of large number of patients at several remotely located participating institutions.

Planning the Size of Clinical Trials with Allowance for Patient Noncompliance

1990 ◽  
Vol 29 (03) ◽  
pp. 243-246 ◽  
Author(s):  
M. A. A. Moussa
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Sample Size ◽  
Event Rate ◽  
Survival Functions ◽  
Time Intervals ◽  
Patient Noncompliance ◽  
Event Rates ◽  
Larger Sample

AbstractVarious approaches are considered for adjustment of clinical trial size for patient noncompliance. Such approaches either model the effect of noncompliance through comparison of two survival distributions or two simple proportions. Models that allow for variation of noncompliance and event rates between time intervals are also considered. The approach that models the noncompliance adjustment on the basis of survival functions is conservative and hence requires larger sample size. The model to be selected for noncompliance adjustment depends upon available estimates of noncompliance and event rate patterns.

The Problems and Promise of Central Pathology Review: Development of a Standardized Procedure for the Children's Oncology Group

2006 ◽  
Vol preprint (2007) ◽  
pp. 1
Author(s):  
Lisa Teot ◽  
Richard Sposto ◽  
Anita Khayat ◽  
Stephen Qualman ◽  
Gregory Reaman ◽  
...  
Keyword(s):  
Oncology Group ◽  
Central Pathology ◽  
Pathology Review
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