Factors Affecting Workload of Cancer Clinical Trials: Results of a Multicenter Study of the National Cancer Institute of Canada Clinical Trials Group

2002 ◽  
Vol 20 (2) ◽  
pp. 545-556 ◽  
Author(s):  
Kathyrn Roche ◽  
Nancy Paul ◽  
Bobbi Smuck ◽  
Marlo Whitehead ◽  
Benny Zee ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Data Collection ◽  
Cancer Treatment ◽  
Multicenter Study ◽  
National Cancer Institute ◽  
Phase Iii ◽  
Study Phase ◽  
Factors Affecting ◽  
Clinical Research Associates

PURPOSE: Increasingly, cancer treatment centers need to be able to estimate specific costs and resources associated with clinical trials. Because the time requirements of trial coordination and data collection are not well known, the Clinical Research Associates (CRA) Committee of the National Cancer Institute of Canada Clinical Trials Group carried out a multicenter study to measure trials’ task times and evaluate the effects of certain factors. METHODS: A data collection instrument was designed and validated before its implementation in the study. Eighty-three CRAs from 24 cancer treatment institutions across Canada collected timing observations of 41 tasks (156 subtasks). Information from all stages of trials activity (protocol management, eligibility and entry, treatment, and follow-up and final stage) was obtained, from initial negotiations to follow-up after study closure. RESULTS: After controlling for stage, phase and sponsor were found to be significant independent factors. Analysis within the stages showed similar patterns. New drug inclusion as a factor was confounded with phase. Industry-sponsored studies had significantly higher overall mean times than did local and cooperative group studies. Early-phase studies required more time than did phase III trials. External sponsorship of any kind increased CRA time more than that necessary for locally coordinated studies, except during the protocol management stage. The burden of a phase I study increased to greater than average once underway and accruing patients. CONCLUSION: Our data demonstrated that sponsor and study phase are important factors to be taken into consideration when estimating clinical trial costs and resource use.

scholarly journals Tobacco Assessment in Actively Accruing National Cancer Institute Cooperative Group Program Clinical Trials

2012 ◽  
Vol 30 (23) ◽  
pp. 2869-2875 ◽  
Author(s):  
Erica N. Peters ◽  
Essie Torres ◽  
Benjamin A. Toll ◽  
K. Michael Cummings ◽  
Ellen R. Gritz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Treatment ◽  
Treatment Outcomes ◽  
Tobacco Use ◽  
Phase Iii ◽  
Cooperative Group ◽  
Group Program ◽  
Status Assessment ◽  
Oncology Practice

Purpose Substantial evidence suggests that tobacco use has adverse effects on cancer treatment outcomes; however, routine assessment of tobacco use has not been fully incorporated into standard clinical oncology practice. The purpose of this study was to evaluate tobacco use assessment in patients enrolled onto actively accruing cancer clinical trials. Methods Protocols and forms for 155 actively accruing trials in the National Cancer Institute's (NCI's) Clinical Trials Cooperative Group Program were evaluated for tobacco use assessment at enrollment and follow-up by using a structured coding instrument. Results Of the 155 clinical trials reviewed, 45 (29%) assessed any form of tobacco use at enrollment, but only 34 (21.9%) assessed current cigarette use. Only seven trials (4.5%) assessed any form of tobacco use during follow-up. Secondhand smoke exposure was captured in 2.6% of trials at enrollment and 0.6% during follow-up. None of the trials assessed nicotine dependence or interest in quitting at any point during enrollment or treatment. Tobacco status assessment was higher in lung/head and neck trials as well as phase III trials, but there was no difference according to year of starting accrual or cooperative group. Conclusion Most actively accruing cooperative group clinical trials do not assess tobacco use, and there is no observable trend in improvement over the past 8 years. Failure to incorporate standardized tobacco assessments into NCI-funded Cooperative Group Clinical Trials will limit the ability to provide evidence-based cessation support and will limit the ability to accurately understand the precise effect of tobacco use on cancer treatment outcomes.

scholarly journals Evaluation of the Value of Attribution in the Interpretation of Adverse Event Data: A North Central Cancer Treatment Group and American College of Surgeons Oncology Group Investigation

2010 ◽  
Vol 28 (18) ◽  
pp. 3002-3007 ◽  
Author(s):  
Shauna L. Hillman ◽  
Sumithra J. Mandrekar ◽  
Brian Bot ◽  
Ronald P. DeMatteo ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Group ◽  
Cancer Treatment ◽  
Randomized Clinical Trials ◽  
Study Drug ◽  
Phase Iii ◽  
Oncology Group ◽  
North Central ◽  
American College Of Surgeons ◽  
Group Trial

Purpose In March 1998, Common Toxicity Criteria (CTC) version 2.0 introduced the collection of attribution of adverse events (AEs) to study drug. We investigate whether attribution adds value to the interpretation of AE data. Patients and Methods Patients in the placebo arm of two phase III trials—North Central Cancer Treatment Group Trial 97-24-51 (carboxyamino-triazole v placebo in advanced non–small-cell lung cancer) and American College of Surgeons Oncology Group Trial Z9001 (imatinib mesylate v placebo after resection of primary gastrointestinal stromal tumors)—were studied. Attribution was categorized as unrelated (not related or unlikely) and related (possible, probable, or definite). Results In total, 398 patients (84 from Trial 97-24-51 and 314 from Trial Z9001) and 7,736 AEs were included; 47% and 50% of the placebo-arm AEs, respectively, were reported as related. When the same AE was reported in the same patient on multiple visits, the attribution category changed at least once 36% and 31% of the time. AE type and sex (Trial Z9001) and AE type and performance status (Trial 97-24-51) were associated with a higher likelihood of AEs being deemed related. Conclusion Nearly 50% of AEs were reported as attributed to study drug on the placebo arm of two randomized clinical trials. These data provide strong evidence that AE attribution is difficult to determine, unreliable, and of questionable value in interpreting AE data in randomized clinical trials.

Measuring the Incremental Cost of Clinical Cancer Research

2001 ◽  
Vol 19 (1) ◽  
pp. 105-110 ◽  
Author(s):  
Dana P. Goldman ◽  
Michael L. Schoenbaum ◽  
Arnold L. Potosky ◽  
Jane C. Weeks ◽  
Sandra H. Berry ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Treatment ◽  
Incremental Cost ◽  
Cancer Patients ◽  
Phase Ii ◽  
The United States ◽  
Phase Iii ◽  
Ongoing Effort ◽  
Cancer Trials ◽  
The Cost

PURPOSE: To summarize evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials. METHODS: A retrospective study of costs will be conducted with 1,500 cancer patients recruited from a randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute–sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750). Costs will be measured approximately 1 year after their trial enrollment from a combination of billing records, medical records, and an in-person survey questionnaire. Similar data will be collected for a comparable group of cancer patients not in trials (n = 750) to provide an estimate of the incremental cost. RESULTS: Evidence suggests insurers limit access to trials because of cost concerns. Public and private efforts are underway to change these policies, but their permanent status is unclear. Previous studies found that treatment costs in clinical trials are similar to costs of standard therapy. However, it is difficult to generalize from these studies because of the unique practice settings, insufficient sample sizes, and the exclusion of potentially important costs. CONCLUSION: Denials of coverage for treatment in a clinical trial limit patient access to trials and could impede clinical research. Preliminary estimates suggest changes to these policies would not be expensive, but these results are not generalizable. The Cost of Cancer Treatment Study is an ongoing effort to provide generalizable estimates of the incremental treatment cost of phase II and phase III cancer trials. The results should be of great interest to insurers and the research community as they consider permanent ways to finance cancer trials.

Dealing With a Deluge of Data: An Assessment of Adverse Event Data on North Central Cancer Treatment Group Trials

2005 ◽  
Vol 23 (36) ◽  
pp. 9275-9281 ◽  
Author(s):  
Michelle R. Mahoney ◽  
Daniel J. Sargent ◽  
Michael J. O'Connell ◽  
Richard M. Goldberg ◽  
Paul Schaefer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Event ◽  
Patient Safety ◽  
Treatment Group ◽  
Cancer Treatment ◽  
Phase Iii ◽  
Small Subset ◽  
North Central ◽  
Normal Limits ◽  
Life Threatening

Purpose Adverse events (AEs) are monitored in clinical trials for patient safety, to satisfy reporting requirements, and develop safety profiles. Recently, much attention has been placed on the reporting of serious AEs (SAEs) that are either life threatening or lethal in clinical trials. However, SAEs comprise a small subset of all AE data collected for trials; the majority of AE data collected are routine AEs (RAEs) regarding non–life-threatening events. We assessed the utility of the RAE data collected, relative to the volume. Patients and Methods We surveyed the RAE data from 26 North Central Cancer Treatment Group coordinated trials. Results A total of 8,318 (11%) of 75,598 of RAEs required queries. Of these, 86% were protocol-required RAEs, 83% of RAEs required per protocol were within normal limits (eg, platelets) or not present, and 61% of extra AEs were mild. One fifth of RAEs were considered unlikely to be related or unrelated to treatment. Overall, 3% of events were severe, life threatening, or caused death. Only 1% of RAE data reported required expedited reporting (eg, via Adverse Event Expedited Reporting System). Results indicate that 72% of RAEs would be eliminated if only the maximum severity per patient and type were required. These results were validated in a large phase III trial. Conclusion The majority of RAEs identified, transcribed, and entered are not clinically important. Our data suggest that reducing the number of AEs monitored will affect substantially neither overall patient safety nor compromise evaluation of regimens undergoing testing. We present several considerations for such a reduction in data collection, as well as a policy that we have used to address the deluge of RAE data.

Developmental Outcomes of Offspring of Adults Treated with Hydroxyurea in the Multicenter Study of Hydroxyurea.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1543-1543 ◽  
Author(s):  
F. Daniel Armstrong ◽  
Martin H Steinberg ◽  
Samir K. Ballas ◽  
Kenneth I. Ataga ◽  
Myron A Waclawiw ◽  
...  
Keyword(s):  
Adaptive Behavior ◽  
Multicenter Study ◽  
Drug Exposure ◽  
Conflicts Of Interest ◽  
Cognitive Outcome ◽  
Phase Iii ◽  
Vineland Adaptive Behavior Scales ◽  
Double Blind ◽  
The Average Range

Abstract Abstract 1543 Poster Board I-566 Between 1992-1995, the National Heart, Lung, and Blood Institute sponsored a multi-center, double blind, randomized, placebo-controlled Phase III clinical trial of hydroxyurea (Multicenter Study of Hydroxyurea-MSH). This trial examined whether hydroxyurea, a myelosuppressive chemotherapeutic agent that also stimulates the production of fetal hemoglobin (HbF), would reduce pain episodes in adults with sickle cell anemia. The trial was stopped early because of significant benefits of pain reduction that was sustained in a nine-year follow-up. This also suggested that patients taking hydroxyurea had improved survival. Despite our best attempts to promote contraception among MSH patients, women had children and men fathered children. One of the concerns about using hydroxyurea was that it might have teratogenic effects on offspring, particularly in the area of brain development and cognitive outcome. To address this question, all eligible adults in the MSH trial were contacted to provide consent to obtain developmental outcome data using telephone interview administration of the Vineland Adaptive Behavior Scales, 2nd Edition, Survey Form (VABS). The population mean for the VABS is 100 with a standard deviation of 15. Interviews were conducted by a trained psychologist using an interactive question and answer process, with probes to clarify any information that was unclear. Consent was obtained for parents of 22 offspring meeting criteria for inclusion. A number of the parents had multiple offspring; eight of the study parents were male and three were female. The children ranged from 6-months to 17 years of age at the time of the VABS interview. Four of the parents could not be reached for the interview. Of the remaining 18, four were ineligible because the birth occurred before hydroxyurea was started. As a group, the offspring were functioning in the average range of development in all areas: Adaptive Behavior Composite (M=102.3), Communication Domain (M=98.5), Daily Living Domain (M=103.8), Socialization Domain (M=100.2), and Motor Domain (for children under age 5; M=108.3). One child was functioning below the average range; follow-up determined that this child was in a special education program but had a developmental disability that had occurred in other family members. The number of children who met criteria for this study and whose parents could be contacted was very small, severely limiting any definitive conclusions about developmental risk for offspring. Studies of teratogenicity for prenatal substance abuse have used standardized observational tests of neurodevelopment; this study relied on parent report, which can be biased if not confirmed. When standardized tests have been used in studies of prenatal drug exposure (not hydroxyurea), subtle difficulties in executive function of offspring have been reported, sometimes years after the exposure. While our results are encouraging in that the offspring in this limited group are functioning in the average range, this observation is not conclusive and there is a need to study a larger sample of children who are offspring of adults treated with hydroxyurea according to community standards. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy of Chemotherapeutic Regimens for Mantle Cell Lymphoma: A Systematic Review of Phase III Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Ali Jaan ◽  
Muhammad Tayyeb ◽  
Farhan Khalid ◽  
Muhammad Khawar Sana ◽  
Zahoor Ahmed ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Cell Transplant ◽  
Mantle Cell ◽  
Combination Regimens

Background: The mainstay treatment for mantle cell lymphoma (MCL) is chemotherapy ± immunotherapy. The standard chemotherapeutic regimens have limited efficacy in MCL when used alone. In this systematic review, we have assessed the efficacy and safety of various combination regimens for the treatment of MCL evaluated in phase III clinical trials. Methods: We performed a comprehensive systematic literature search on PubMed, Embase, clinicaltrials.gov, and Web of Science databases with the date of inception to May 2020. We used MeSH (Medical Subject Headings) terms for "mantle cell lymphoma", "treatment outcome" along with their keywords, and combined their results. Our search generated a total of 3572 articles. After excluding case reports, case series, observational studies, review articles, meta-analysis, phase I/II clinical trials, and pre-clinical studies, we included five phase III randomized clinical trials (RCTs) reporting the efficacy of combination regimens for MCL treatment. Results Data from five phase III RCTs was pooled with total N=1683 (newly diagnosed (ND), n=1242, relapsed/refractory (RR), n=441). 1610 patients were evaluable. Kluin-Nelemans et al. 2020 (n=560) studied induction with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) vs R-FC (rituximab, fludarabine, and cyclophosphamide) for ND-MCL with follow-up on maintenance with rituximab (R) -vs interferon alfa. At a median follow up of 7.6 years (y), median overall survival (mOS) was 6.4 vs 3.9 y (p=0.0054) in R-CHOP vs R-FC group, respectively. The median progression-free survival (mPFS) and mOS in the R-CHOP cohort on R maintenance were significantly better when compared to those on interferon alfa maintenance (mPFS, 5.4 y vs 1.9 y, p<0.001) (mOS, 9.8 y vs 7.1 y, p=0.0026). Robak et al. (2015) (n=487) assessed bortezomib in ND-MCL by substituting it for vincristine in the standard R-CHOP therapy. A cohort of MCL ineligible for stem cell transplant (SCT) was randomly assigned to either R-CHOP or VR-CAP (bortezomib replacing vincristine). At a median follow-up of 40 months (mo), mPFS was 24.7 mo vs 14.4 mo in VR-CAP vs R-CHOP (HR 0.63, p<0.001), respectively. Similar, relative improvements were reported in complete response (CR) (53% vs 42%, p=0.007) and 4-year OS was (64% [95% CI 56-71] vs 54% [95% CI 45-62]). Jin et al. (2018) (n=121) assessed R-CHOP vs VR-CAP in ND-MCL patients ineligible for SCT. After a median follow-up of 42.4 mo, mPFS for VR-CAP was better than R-CHOP (28.6 mo vs 13.9 mo, HR=0.7, p=0.157). The overall response rate (ORR) was almost similar in VR-CAP (97%) and R-CHOP (98%). The 4-year OS was 62% vs 61% in VR-CAP vs R-CHOP, respectively. Flinn et al. (2014) (n=74) studied the efficacy of bendamustine in combination with rituximab (BR) vs R-CHOP or R-CVP (R-CHOP minus doxorubicin) as induction regimens in ND-MCL. 36 patients received BR and 38 patients received R-CHOP/R-CVP. ORR was 94% vs 85% with BR vs R-CHOP/R-CVP, respectively. Hess et al. (2009) (n=162) evaluated temsirolimus in RR-MCL. The study population was randomized to either 175/75mg temsirolimus (arm A), 175/25mg temsirolimus (arm B), and the investigator's choice of chemotherapy (arm C). The mPFS was significantly better in arm A compared to arm C (4.8 mo vs 1.9 mo, HR 0.44 [97.5% CI 0.25-0.7], p=0.0009). Arm B had slight improvement but insignificant. Similarly, mOS was 12.8 mo in arm A (HR 0.8 [95% CI 0.5-1.28], p=0.35), and 8.8 in arm B (HR 0.96 [95% CI 0.60-1.54], p=0.87), when compared to 9.5 mo in arm C. Drelying et al. (2016) (n=280), studied temsirolimus in comparison with ibrutinib, RR-MCL with mPFS of 14.6 mo (95% CI 10.4-not estimable) vs 6.2 mo (95% CI 4.2-7.9), respectively. Toxicities were typically manageable. VR-CAP was associated with a higher incidence of toxicity (100%) vs R-CHOP (94%) majority of which was hematological. Thrombocytopenia was particularly more prominent with temsirolimus. Granulocytopenia was persistent in 30-40% in the R-FC cohort after 5 y. Conclusion: The chemo-immunotherapy combination is favorable compared to chemotherapy alone for the treatment of MCL. R-CHOP induction followed by rituximab maintenance in MCL shows favorable long-term safety and efficacy profile. Bortezomib substituting for vincristine in R-CHOP improves the efficacy outcomes. Ibrutinib-based regimens are superior to temsirolimus-based regimens. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

scholarly journals Use of routinely collected health data in randomised clinical trials: comparison of trial-specific death data in the BOSS trial with NHS Digital data

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sharon B. Love ◽  
Anna Kilanowski ◽  
Victoria Yorke-Edwards ◽  
Oliver Old ◽  
Hugh Barr ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Oesophageal Cancer ◽  
Health Data ◽  
Digital Data ◽  
Phase Iii ◽  
Specific Data ◽  
Routinely Collected Health Data ◽  
Death Data

Abstract Background A promising approach to reduce the increasing costs of clinical trials is the use of routinely collected health data as participant data. However, the quality of this data could limit its usability as trial participant data. Methods The BOSS trial is a randomised controlled trial comparing regular endoscopies versus endoscopies at need in patients with Barrett’s oesophagus with primary endpoint death. Data on death and cancer collected every 2 years after randomisation (trial-specific data) were compared to data received annually (all patients on one date) from the routinely collected health data source National Health Service (NHS) Digital. We investigated completeness, agreement and timeliness and looked at the implications for the primary trial outcome. Completeness and agreement were assessed by evaluating the number of reported and missing cases and any disparities between reported dates. Timeliness was considered by graphing the year a death was first reported in the trial-specific data against that for NHS Digital data. Implications on the primary trial outcome, overall survival, of using one of the data sources alone were investigated using Kaplan-Meier graphs. To assess the utility of cause of death and cancer diagnoses, oesophageal cancer cases were compared. Results NHS Digital datasets included more deaths and often reported them sooner than the trial-specific data. The number reported as being from oesophageal cancer was similar in both datasets. Due to time lag in reporting and missing cases, the event rate appeared higher using the NHS Digital data. Conclusion NHS Digital death data is useful for calculating overall survival where trial-specific follow-up is only every 2 years from randomisation and the follow-up requires patient response. The cancer data was not a large enough sample to assess usability. We suggest that this assessment of registry data is done for more phase III RCTs and for more registry data to get a more complete picture of when RCHD would be useful in phase III RCT. Trial registration ISRCTN54190466 (BOSS) 1 Oct 2009.

Phase II Trial of N,N-Diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl and Doxorubicin Chemotherapy in Metastatic Breast Cancer: A National Cancer Institute of Canada Clinical Trials Group Study

1999 ◽  
Vol 17 (11) ◽  
pp. 3431-3437 ◽  
Author(s):  
K. Khoo ◽  
L. Brandes ◽  
L. Reyno ◽  
A. Arnold ◽  
S. Dent ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
National Cancer Institute ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Metastatic Breast ◽  
Phase Iii

PURPOSE: This multicenter phase II trial investigated the efficacy and toxicity of a combination of the novel intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl (DPPE), and doxorubicin in patients with anthracycline-naïve metastatic breast cancer. Preclinical models and early single institutional studies suggested DPPE could potentiate the cytotoxicity of doxorubicin. PATIENTS AND METHODS: Forty-two women, 32 to 77 years old (median, 59 years), with anthracycline-naïve metastatic breast cancer were treated. Patients may have had one previous regimen of nonanthracycline chemotherapy, either in the adjuvant or metastatic disease treatment setting. DPPE (6 mg/kg) was administered as an 80 minute intravenous infusion with doxorubicin (60 mg/m2) given intravenously over the last 20 minutes of the DPPE infusion. Patients were premedicated with an antiemetic and sedating regimen. The DPPE/doxorubicin treatment was given every 21 days for a maximum of seven cycles. RESULTS: All 42 patients were assessable. Overall, toxicity was comparable to that expected with doxorubicin alone, with the exception of DPPE-related motion sickness, mild hallucinations, and cerebellar signs at the time of the infusion. These CNS side effects were manageable in an ambulatory care setting, improved with subsequent cycles of treatment, and did not usually require hospitalization. Four patients developed febrile neutropenia. Thirty-five patients received four or more cycles of chemotherapy. The overall response rate was 52.5% (95% confidence interval, 36% to 68%), with 9.5% complete responses (n = 4), 43% partial responses (n = 18), and 38% of patients with stable disease (n = 16). CONCLUSION: The antitumour effects of DPPE/doxorubicin the 52.5% response rate seems encouraging, particularly in consideration of the fact that a recently reported randomized National Cancer Institute of Canada Clinical Trials Group trial using single-agent doxorubicin 60 mg/m2 in one of the treatment arms achieved a 31% response rate. Thus, a randomized phase III trial of doxorubicin versus doxorubicin plus DPPE is being conducted in this clinical setting.

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