bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of poor prognostic features on the surgical treatment of breast cancer in an intergroup adjuvant chemotherapic trial
Authors: Pockaj B. A. , Dueck A. , Tenner K. , Perez E.
Published: March 2020

612

Background: The adoption of new breast surgical techniques has been rapid for early stage breast cancer. The utilization of these techniques in patients with high risk operable breast cancer has not been thoroughly investigated. Methods: Retrospective surgical data was summarized for patients entered into N9831 “Phase III Trial of Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel With or Without Trastuzumab as Adjuvant Treatment for Women With HER-2 Over-expressing or Amplified Node Positive or High-Risk Node Negative Breast Cancer.” Results: 3,505 patients were entered into N9831 from 2000–2005 following primary surgery for breast cancer. The median age was 50 and 43% were premenopausal. 93% of patients underwent a diagnostic biopsy prior to their definitive surgical procedure. Whether HER2-neu status was available at time of definitive surgery is unknown. 61% underwent a mastectomy whereas 39% underwent breast conserving surgery (BCS). The rate of BCS was relative stable over the course of the trial. Patients with T1 tumors had a higher rate of BCS (49%) compared to T2 tumors (37%) and T3 tumors (6%). Sentinel lymph node (SLN) biopsy was performed in 54% of the cases. The rate of SLN biopsy increased from 40% in 2000 to 66% in 2005. Patients who underwent mastectomy had a lower rate of SLN biopsy than patients who underwent BCS (44% versus 71%, respectively). Tumor size was also associated with the rate of SLN biopsy: T1 (60%), T2 (53%), and T3 (36%). Data on local and regional recurrences are still maturing. Conclusions: Surprisingly, low numbers of patients on this trial underwent BCS whereas the adoption of the SLN biopsy procedure among the same group of surgeons was relatively high. The relatively low rate of BCS in this study population needs further investigation to determine what surgeon and patient factors impacted the surgical decision.

No significant financial relationships to disclose.
Perception of African American men of their likelihood of a cancer diagnosis at the time of prostate biopsy
Authors: Dale W. , Hemmerich J. , Ahmad F. , Meltzer D.
Published: March 2020

6503

Background: Men are supposed to have an “informed discussion” before undergoing PCa screening. African Americans (AA) are diagnosed at later stages of prostate cancer (PCa) than their white counterparts. We studied racial differences in self-prediction compared with actual likelihood of positive biopsy. Method: Face-to-face surveys with patients (n = 172), referred after screening positive for possible PCa, were conducted in urology clinics at the time of biopsy. The surveys include socio-demographics, general anxiety (Hospital Anxiety and Depression Scale), disease-specific anxiety (Memorial Anxiety Scale for Prostate Cancer), and self-estimated likelihood of a positive biopsy. Medical records were reviewed for biopsy results. Results: Average age was 63±7.9, AA comprised 39% of the sample, and 56% had at least a college degree. The overall rate of positive biopsy was 55%, with AA being much more likely to have a positive biopsy (70% vs. 44%; p< 0.05). Despite being referred for biopsy for concern about PCa, 37% of the men indicated that they had a 0% likelihood of having prostate cancer (i.e. that it was impossible), and AA were more likely than whites to say this (58% vs. 24%; p < 0.01). In a logistic regression with important covariates, patients’ ratings of their likelihood of PCa diagnosis were not predictive of a positive biopsy, while older age, higher PSA score, and lower self-rated health were. Generalized anxiety was not correlated with estimated likelihood of having PCa, but cancer-specific anxiety was correlated (p = 0.02). Neither was correlated with likelihood of having PCa. Conclusion: AA are more likely to have PCa at biopsy than whites. Both groups dramatically underestimate their statistical likelihood of having PCa at the time of biopsy. More concerning, AA estimates are lower, yet their likelihood is higher.

No significant financial relationships to disclose.
Standard therapy deviations in the practice of clinical oncology
Authors: Rivarola E. G. , Gil Deza E. , Negro A. , Morgenfeld E. , Juarez D. , García Gerardi C. , Santillán D. , Gercovich F. G.
Published: March 2020

6504

Background: “Errors can be prevented by designing systems that make it hard for people to do the wrong thing and easy for people to do the right thing” (To Err is Human: Building a Safer Health System - report from the Institute of Medicine- USA). The current paper was designed to evaluate, prospectively, the different types of prescription deviation from standards as well as the way they are worked out in the daily practice. Methods: Between October 2004 and December 2006, the Tx of 6611 patients ( pt) were progressively entered into a database and compared with the national and international Tx recommendations (Evidence Based Oncology). The deviations between actual and recommended Tx were classified in two groups: Type I, or deviation from “Gold standard” (Off label prescription, experimental treatments or application of translational research with no evidence of better results regarding survival and/or quality of life over a standard Tx) and Type II, or medical errors with high malpractice risk (misdiagnosis, or drug prescription error in dosage, administration or schedule). The deviation was then pointed out to the attending physician, and their response was catalogued as: “A” (Immediate Correction), ‘B‘ (Administrative appeal to determine the treatment) or “C” (Court appeal to determine the treatment). Results: Eight hundred and sixty two errors were identified in the 6611 pt (13%). Six hundred and forty four (74,7%) were Type I and 218 (25,3%) were Type II.. The physicians were more reluctant to recognize Type I than Type II deviations. The response to the deviations were the following: Type I, response A= 454 cases (71%), Type I, response B 184 cases (28%), Type I, response C: 6 cases (1%). Type II response A: 196 cases (90%), Type II response B: 22 cases (10%). Type II response C: 0. Conclusions: 1) The implementation of a treatment-supervision system is the first step towards providing safer health care in oncology. 2) The 644 Type I prescriptions deviation appear to increase in relation to diffusion of innovations, and their modification is more conflictive. However, 71% are corrected immediately. 3) The 218 Type II prescriptions deviation appear to be related with medical expertise, and their resolution is simpler (90 % with immediate correction). An exhaustive taxonomy of deviations will be presented.

No significant financial relationships to disclose.
Trends in the quality of external beam radiotherapy for elderly men with localized prostate cancer
Authors: Bekelman J. E. , Zelefsky M. J. , Jang T. L. , Basch E. M. , Schrag D.
Published: March 2020

6507

Background: External beam radiotherapy (EBRT) is a commonly used for treatment of clinically localized prostate cancer. Yet, secular trends in the delivery of this highly technical therapy have received little attention. Methods: Using data from the linked Surveillance, Epidemiology, and End Results (SEER) Medicare program, we evaluated trends in five EBRT quality measures among 23,018 patients age 65 or older diagnosed from 1994 to 2002 with clinically localized prostate cancer and treated with primary EBRT. Using tumor registry data from SEER and Medicare claims, we excluded 6,956 patients who received brachytherapy and 7,009 patients who received combination EBRT and brachytherapy. We identified treating radiation oncologists via unique physician identification numbers reported on claims and obtained board certifications from the AMA Masterfile. We assessed the five EBRT quality measures proposed by a RAND expert panel that were amenable to analysis using SEER-Medicare data: 1) use of conformal radiotherapy treatment planning; 2) use of high-energy (=10MV) photons; 3) use of custom immobilization; 4) radiation oncologist board certification; and 5) completion of two follow-up visits with a radiation oncologist in the year following therapy. Results: As shown in the table , conformal radiotherapy increased over the study period. Approximately one-third of patients received consistent follow-up from a radiation oncologist in the year following therapy. Notably, however, claims data revealed that 80% of patients completed at least two follow-up visits with either urologists or radiation oncologists. Conclusions: Conformal radiotherapy is now routine for elderly men with localized prostate cancer. Observed practice patterns deviate from the RAND metric for patient follow-up, suggesting that this measure merits clarification. Future research should examine whether variation in receipt of these quality measures affects important clinical outcomes.

No significant financial relationships to disclose.

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Questionable value of attribution when interpreting adverse event data: A joint evaluation by North Central Cancer Treatment Group (NCCTG) and American College of Surgeons Oncology Group (ACOSOG)
Authors: Hillman S. L. , Sargent D. J. , Bot B. M. , DeMatteo R. P. , Perez E. A. , Ballman K. V. , Mandrekar S. J.
Published: March 2020

6511

Background: In March 1998, the Common Toxicity Criteria (CTC) version 2.0 introduced the collection of attribution of adverse events (AE) to study drug. Collection of attribution adds time and cost to the clinical trial process, and reporting in the literature has varied. At ASCO 2006 results were presented from NCCTG trial 97–24–51 that showed ∼ 50% of events on the placebo arm were reported as attributed to study drug and 25% of the time the same event was not consistently attributed. We sought to validate these results in a second placebo controlled trial. Methods: Patients on the placebo arm of the phase III ACOSOG trial Z9001 (imatinib mesylate vs. placebo after resection of primary gastrointestinal stromal tumors) were evaluated since the reported AEs could not be due to study drug. Attribution was collected per CTCv3.0 as not related, unlikely, possibly, probably, or definitely related, and categorized as “unrelated” (not related or unlikely) and “related” (possible, probable, or definite). Patterns were evaluated using generalized estimating equations adjusting for multiple events per patient. Results: 202 patients and 2871 AEs were included. 52% of AEs were reported as “related”. Known imatinib AEs were more likely to be reported as “related”. The reported rate of AE relatedness varied by AE type. No patterns were observed by gender, age, PS, severity or visit of AE. When the same event was reported on the same patient on multiple visits, the attribution category changed at least once 33% of the time with 19% changing from “related” to “unrelated” or vice versa. Conclusion: 52% of events on the placebo arm of Z9001 were reported as attributed to study drug and 19% of the time the same event was not consistently attributed. These data provide further evidence that attribution is difficult to determine, unreliable, and of questionable value in interpreting randomized clinical trials.

No significant financial relationships to disclose.

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Statistical power of negative randomized clinical trials (RCTs) presented at the American Society of Clinical Oncology (ASCO) Annual Meetings
Authors: Bedard P. , Krzyzanowska M. K. , Pintilie M. , Tannock I. F.
Published: March 2020

6516

Background: Underpowered randomized clinical trials (RCTs) may expose participants to risks and burdens of research without scientific merit. We investigated the prevalence of underpowered RCTs presented at ASCO annual meetings. Methods: We surveyed all two-arm parallel phase III RCTs presented at the ASCO annual meeting from 1995–2003 where differences for the primary endpoint were non-statistically significant. Post hoc calculations were performed using a power of 80% and a=0.05 (two-sided) to determine the sample size required to detect a small, medium, and large effect size between the two groups. For studies reporting a proportion or time to event as a primary endpoint, effect size was expressed as an odds ratio (OR) or hazard ratio (HR) respectively, with a small effect size defined as OR/HR=1.3, medium effect size OR/HR=1.5, and large effect OR/HR=2.0. Logistic regression was used to identify factors associated with lack of statistical power. Results: Of 423 negative RCTs for which post hoc sample size calculations could be performed, 45 (10.6%), 138 (32.6%), and 333 (78.7%) had adequate sample size to detect small, medium, and large effect sizes respectively. Only 35 negative RCTs (7.1%) reported a reason for inadequate sample size. In a multivariable model, studies presented at plenary or oral sessions (p<0.0001) and multicenter studies supported by a co-operative group were more likely to have adequate sample size (p<0.0001). Conclusion: Two-thirds of negative RCTs presented at the ASCO annual meeting do not have an adequate sample to detect a medium-sized treatment effect. Most underpowered negative RCTs do not report a sample size calculation or reasons for inadequate patient accrual.

No significant financial relationships to disclose.
Myths in the assessment of progression: How frequently should we assess patients in clinical trials?
Authors: Stone A. M. , Fernandes N. , Morris C.
Published: March 2020

6521

Background: It is often believed that within a clinical trial a patient’s progression status should be assessed as frequently as practically possible if the primary objective is to compare progression-free survival (PFS). However, the statistical analysis of PFS data compares rates of progression rather than a specific percentile such as a median, and results in an estimate of the hazard ratio (HR)—the ratio of event rates. Methods: We provide results of simulations assessing the power and bias of an analysis of PFS in controlled trials according to visit frequency, rate of progression and analysis method. The simulations assume a true HR of 0.8 and that data are analyzed after 630 patients have an event to provide a nominal power of 80%. All simulations assume patients are assessed according a symmetric visit schedule as otherwise, if data are analyzed asymmetrically, bias will follow (Proc Am Assoc Cancer Res 2002; abst 975). Results: If patients are assessed at a time interval equal to the median divided by two, there is a negligible (=2%) loss of power for the analysis of PFS data. Data presented in the table show that in a disease with a comparator median of 4 and 8 months when 1,000 patients are randomized, there is little increase in power if patients are assessed more often than every 2 and 4 months, respectively, using a standard log- rank test. The simulations presented assume there is some variability (SD=1 week) of the actual assessment date around the protocolled date. If PFS data are analyzed by moving PFS times to the scheduled assessment time, alternative methods of analysis (grouped survival techniques) preserve power and avoid bias by appropriately handling the excessively tied PFS times. Conclusions: Within the context of a clinical trial, a fully powered analysis of PFS is possible if patients are assessed at a frequency which is one-half of the median of the disease under study, and therefore patients need not be assessed more frequently unless clinical practice outside of a clinical trial would dictate otherwise.

[Table: see text] [Table: see text]
Inter-observer variability in chemotherapy trials for pancreatic cancer
Authors: Baumann B. C. , Ford R. , Dasse K. , Zhou K.
Published: March 2020

6522

Background: No studies have examined differences in imaging assessment of drug response for unresectable pancreatic cancer between investigators and independent central review panels. This study reports such discrepancies. Methods: 133 patients in two multi-center, randomized Phase II drug trials had their response assessed by measurement of tumor size or new lesions on serial CT scans. Protocols specified techniques for tumor measurement and defined responses as complete (CR) or partial responses (PR), stable (SD) or progressive disease (PD). Objective responses were confirmed by repeat imaging evaluations after an interval > 4 weeks. Cases of PR or SD withdrawn from the study <8 weeks after enrollment were scored as non-evaluable (NE). The same images were then blindly reviewed by protocol trained radiologists at an Independent Core Lab. Cases of discordance in the interpretation of best response between investigators and reviewers were then blindly re-reviewed by an independent adjudicator. Results: In 50/133 cases (38%), there was sufficient discrepancy between investigators and reviewers to result in a change in overall response. In 10 cases (8%), investigators reported responses inconsistent with protocol standards for their tumor measurements. In 40 cases (30%), reviewers disagreed with the radiological findings of the investigators. In 47 of the 50 cases, the films were available for a second review by the adjudicator who confirmed the reviewers’ assessment of response in 39/47 (83%) of cases. Discrepancies in assessment of response were not randomly distributed. Investigators reported significantly more confirmed objective responses (CR + PR) than reviewers even after investigators’ response coding errors were corrected. As shown in Table 1 , investigators reported favorable responses in 21/133 (16%) cases compared with 6/133 (5%) responses noted by reviewers (p=0.01). Conclusions: The results support the use of independent review of trial data when the endpoint of the trial (response rate) is based on imaging data.

[Table: see text]
A retrospective exploratory study of the variability of radiologists’ measurements in a selected subgroup of subjects enrolled in a clinical trial
Authors: Ford R. W. , Ford R. R. , Zhou K.
Published: March 2020

6523

A retrospective exploratory study of the variability of radiologists’ measurements in a selected subgroup of subjects enrolled in a clinical trial Background: Independent centralized review of imaging studies is an established means of validating data used in support of corporate ‘go-no go‘ decisions, regulatory approval, and post marketing claims. Despite best efforts at standardizing this process using the Response Evaluation Criteria in Solid Tumors (RECIST), there will be inherent differences in radiologic measurements. To define a concise value for the variation between a specific set of radiologists, the following study was performed. Methods: An experienced radiologist and a research intern reviewed digital Computerized Tomographic (CT) scans from 31 subjects to identify 150 primary and metastatic tumors. Tumors were categorized into 4 categories. [Category (Cat.) 1 - Defined Edge/Radially Symmetric, Cat. 2 - Defined Edge/Irregular Shape, Cat. 3 - Blurred Edge/Radially Symmetric, Cat. 4 - Blurred Edge/Irregular Shape] Fifteen radiologists independently measured each tumor. Mixed effects models controlling for different tumors were used to assess the variance. Results Overall, the between reader variations accounted for 4.15% percent of total errors for the length. The respective between reader and the random errors are 0.32 (95% CI: 0.14, 0.77) and 7.51 (95%CI: 7.08, 8.01). The data shows that the variances are smallest for category 1 tumors (total error: 1.45) and largest for category 4 tumors (total error: 20.79). The total error for categories 2 and 3 are listed in Table 1 below. Conclusions The (low reader error) / (total error) verifies that the radiologists were only responsible for a small portion of the total error, and suggests these 15 radiologists measuring a tumor will be comparable to one of these radiologists measuring the tumor many times.

No significant financial relationships to disclose.

[Table: see text]
Screening cancer patients for clinical trial eligibility: A randomized study
Authors: Wright J. , Whelan T. , Julian J. , Simunovic M. , Levine M.
Published: March 2020

6529

Background: The overall proportion of cancer patients enrolled into clinical trials is undesirably low. Research suggests many aspects of the recruitment process can be improved. The present study was undertaken to evaluate the benefit of identifying potentially eligible (PE) clinical trial patients for physicians. Methods: Consenting physicians were randomized to 26 weeks of screening support or not, and were then crossed-over to the other strategy for a second 26-week time period. A computer program reviewed new patient consultations to identify PE clinical trial patients. Physicians receiving support were provided with written individualized details of patient eligibility for trials prior to their medical consultation. The primary outcome of interest was the difference, by physician, in the number of patients who were approached for consent to enter a clinical trial. Results: Thirty-six physicians participated in the 52-week study. 5051 consultations were screened in a blinded fashion, 2,376 when physicians had support and 2,675 when they did not. 939 of 2,376 (39.5%) consultations were identified as involving PE patients when physicians were receiving support, and 1,061 of 2,675 (39.7%) when without. The primary outcome of the study, by physician, did not demonstrate a statistically significant improvement, with 4.1 patients per physician without vs. 4.7 patients with screening support (p>0.05). Secondary analysis demonstrated that the overall proportion of patients approached with the clinical trial option increased from 149/2,675 (5.6%) to 169/2,376 (7.1%) with screening support (Chi-square, p=0.024) and that the number of patients that entered a clinical trial also increased from 60/2,675 (2.2%) to 83/2,376 (3.5%) (Chi-square, p=0.007). Conclusions: This study suggests that individualized patient screening for clinical trial eligibility may be useful to improve the numbers of patients approached to consider clinical trials. The number of new patients that entered clinical trials remained low, and ongoing research to facilitate improvements is required.

No significant financial relationships to disclose.
Expanding participation to non-group members in phase III cooperative group treatment trials
Authors: Denicoff A. M. , Hopkins J. R. , Riordan S. E. , Adler J. M. , Marinucci D. M. , Geisen K. , Lambersky R. , Catalano R. B. , Mooney M. M. , Abrams J. S.
Published: March 2020

6533

Background: The NCI initiated the Cancer Trials Support Unit (CTSU) Independent Clinical Research Site (CICRS) Program at the ASCO Annual meeting in 2002. Building upon the CTSU's initial aim to expand participation of any NCI-sponsored Cooperative Group (Group) phase 3 trial to all Group and Community Clinical Oncology Program (CCOP) members, the CICRS initiative has enabled unaffiliated sites to enroll patients in a wide variety of Group trials. Methods: Interested oncology practices submitted applications that were reviewed by a committee, including external reviewers, to select the most qualified sites. They had to meet standards similar to those for Group members and were assessed for the quality of investigator credentials and site preparedness. Sites were required to demonstrate functioning IRBs, pharmacy facilities, and data management standard operating procedures to ensure a high level of clinical trials practice. A CTSU research nurse mentor was added to address challenges faced by the sites. Sites were required to enroll at least 5 patients per year to remain active participants. Results: Via the CTSU, a trial menu of over 60 Group phase 3 studies, and selected phase 2 trials, were made available to CICRS participants. Active CICRS sites are distributed over 19 states and 6 of the 7 highest accruers are in population areas with less than 300,000 persons. Participating sites were surveyed in January 2006 to better understand barriers to clinical trials enrollment and 68% percent reported the main barriers were dedicated staff, time, adequate IRB and financial support for research. Conclusions: Obstacles for participation in the CICRS program have been defined and strategies to overcome them are being implemented. Results of these efforts will be updated, including provision of survey results, updated accrual, audit results and a review of successful enrollment strategies.

No significant financial relationships to disclose.

[Table: see text]
The use of telemedicine to care for cancer patients at remote sites
Authors: Taylor M. , Khoo K. , Saltman D. , Bouttell E. , Porter M.
Published: March 2020

6538

Background: At the BC Cancer Agency -CSI we are challenged to provide systemic cancer care to a population of 720,000 widely dispersed over 250,000 square kilometers. Video-link technology (VT) has been used at our centre since April 2004 to help provide distant care and prevent patient and physician travel. Methods: Patients gave consent for the use of VT. We prospectively collected data on patient and physician experiences as part of on-going quality assurance. We retrospectively collected the clinical data on these patients. Results: We performed 104 encounters on 100 patients between April 2, 2004 and October 4, 2006. Patient characteristics: female 62%, male 38%, average age was 66 years with a range of 28 –83. Extent of cancer was 67% curable, 31% advanced and 7% unknown. Visit type and cancer sites are shown below. Patients rated this experience very highly and the vast majority would repeat the experience rather than travel or wait several weeks to see the doctor in person. Physicians were not as satisfied as the patients; and both groups expressed a concern about the need for physical exam. In those having a consult, 54% had an exam within 60 days, and in none of these patients were the treatment recommendations changed. The majority (57%) of those consult patients that didn’t have an exam had either Stage 0 or I breast cancer or Stage II or III colorectal cancer; and it seems unlikely that physical exam would have changed management in these patients. Conclusions: We were able to deliver cancer care at distant sites with VT and patients found the experience very acceptable. There may not be a need for repeat physical exam in these patients, who had previously been examined by other physicians, prior to referral.

No significant financial relationships to disclose.

[Table: see text]
Chemotherapy (CT) dose adjustment for obese or elderly patients: How often does it occur, and should it? Results of an Australian survey
Authors: Field K. M. , Kosmider S. , Jefford M. , Jennens R. , Michael M. , Green M. , Gibbs P.
Published: March 2020

6539

Background: Determining the optimal starting dose of chemotherapy (CT) for an individual patient (pt) presents a considerable challenge and is generally empirical. While body surface area (BSA)-based dosing has major limitations, it is standard practice worldwide. It may perform particularly poorly in certain scenarios, including the obese or elderly pt, representing an increasing area of clinical practice. We sought to determine the range of approaches employed by medical oncologists Australia-wide when administering CT to these pts. Methods: A questionnaire was developed by a panel of oncologists and mailed to all members of the Medical Oncology Group of Australia. The survey was designed to document the methods of calculating CT doses, with an emphasis on the parameters utilised and also factors considered in a variety of settings, including obese and elderly pts. Results: Evaluable responses were obtained from 181 of 315 medical oncologists and fellows (RR 57.5%). BSA-based dosing was reported as standard practice by 176 (97.2%). In the adjuvant disease setting, 23 (12.7%) use ideal rather than actual body weight (BW), or whichever is less, when prescribing CT. 14.5% (n=25) defined ideal BW as a body mass index (BMI) of 27, while 41% chose BMI 20–25 as ideal. When treating the obese pt (BMI>30), only 6.2% of respondents routinely use actual BW. Of the remainder, 69.5% either routinely cap the dose at 2m2 or use ideal BW, and 16.4% cap at a maximum dose or at a different BSA. In underweight (BMI<18.5) pts conversely, 95% (n=171) routinely use BSA based on actual BW. 41 respondents (22.7%) routinely dose reduce in the fit elderly population. Conclusions: Many current methods of BSA-based CT dosing demonstrated in this survey are not supported by the available literature. There is strong evidence from adjuvant studies in breast and bowel cancer that actual BSA is desirable; we clearly demonstrate that a substantial number of Australian patients, especially the obese, are being under-dosed, potentially leading to inferior outcomes. Until alternative methods to BSA-based CT dosing are available, education regarding the appropriateness of routine dose adjustments in specific circumstances is urgently required.

No significant financial relationships to disclose.
Medication safety in cancer clinical trials: An analysis of medication error reports at a comprehensive cancer center
Authors: Kane M. P. , Fessele K. , Gordilis-Perez J. , Schwartz S. , Lisi S. , Nishioka J. , Vamos D. , Tan A. , Cunningham R. , Goodin S.
Published: March 2020

6547

Background: Although medication errors comprise 10–25% of all medical errors, little is known concerning the occurrence or types of medication errors occurring while treating patients on a clinical trial. Therefore, we retrospectively reviewed the medication errors reported in patients enrolled on clinical trials at our center. Methods: As part of a multidisciplinary continuous quality improvement project, from January 2003 through December 2006, we collected voluntary reports of medication errors in adult and pediatric patients on clinical trials involving both oral and intravenous chemotherapy. All reports were classified prospectively regarding clinical trial involvement, severity category (A to I) per the National Coordination Council on Medical Error Reporting and Prevention, type, cause, and where in the medication use process the error occurred. Results: There were 163 reports involving patients treated on clinical trials. The most common errors were those corrected prior to reaching the patient in 68% of events (Category A&B), while 31% reached the patient but did not result in harm (Category C&D), with 1% resulting in temporary patient harm (Category E&F). The most common type of errors were prescribing (66%), improper dose (42%), and omission errors (9%). Not following an institutional procedure or the protocol was the primary cause for these errors (39%), followed by the written order (30%), and poor communication involving both the healthcare team and the patient (26%). The processes where the errors initiated were in prescribing 47%, administration 10%, dispensing 6%, and monitoring 5%. Conclusion: Medication errors do occur in clinical trials, however the majority of these are corrected prior to reaching the patient or do not result in harm. Not following an institutional procedure or the protocol was the most common cause of error. This is most likely due to the protocol procedures differing from existing standards of care. Protocol-specific education through the Centralized Education and Training Service, a shared resource within our cancer center, addresses this issue enhancing the quality and safety of clinical trials through the education and training of healthcare professionals.

No significant financial relationships to disclose.
Cost containment in oncology: A single-centre model for drug waste reduction
Authors: Aita M. , Aprile G. , Follador A. , Mansutti M. , Marini L. , Mattioni L. , Tosolini M. , Fasola G.
Published: March 2020

6557

Background: To control costs while maintaining or improving the quality of patient care is challenging for physicians and health care managers. The problem has become critical in oncology, due to the increasing number of cancer cases and the recent availability of new drugs, with a dramatic rise in health care expenditure. Here we report the experience of our Medical Oncology Department, where centralization of chemotherapy (CT) manufacturing and development of a computerized physician order-entry (CPOE) system allowed an effective planning of CT services with a substantial waste minimization and a significant cost saving. Methods: Starting January 2005 we collected data about drug demand, real consuming and resulting wastes and quantified the economic value of drug leftovers. Finally, based on a web literature search and a survey among other Cancer Services, an internal protocol for waste limitation was developed. Main adopted measures were: 1) a rational, per pathology distribution of CT sessions over the week, allowing waste recovery while respecting drug stability; 2) the use of multi-dose vials, that maintain microbial and chemical stability for up to 28 days; 3) a reasonable dose rounding, to fit with available vial sizes/leftovers; 4) the selection of the most convenient vial size when more options are available. Results: The baseline analysis focused on 29 drugs over a 1-year period. Considering their price per milligram and the amount of wastes, we found that 74% of the expense was attributable to six compounds only (cetuximab, docetaxel, gemcitabine, oxaliplatin, pemetrexed and trastuzumab) and that the economic loss due to their waste equaled 4.5% of the annual drug expenditure. Following the application of the above listed measures, the monetary loss due to unused drugs showed an impressive 45% reduction throughout 2006. Conclusions: Our experience may represent an accessible model in addressing the issue of cost rising in oncology. A critical evaluation and planning of CT daily workload, provided by CPOE, and a multidisciplinary effort to pursue specific waste reduction strategies produce a relevant cost saving.

No significant financial relationships to disclose.
Cost-effectiveness of primary prophylaxis (PP) with colony-simulating factor (CSF) when compared with secondary prophylaxis (SP) in elderly patients with diffuse aggressive lymphoma undergoing curative chemotherapy
Authors: Chan K. K. , Imrie K. R. , Alibhai S. M.
Published: March 2020

6558

Background: The 2006 ASCO guideline recommends PP with CSF for elderly patients with diffuse aggressive lymphoma, partially based on previous cost-minimization analyses showing that CSF saved costs when compared with no CSF by reducing hospitalization from febrile neutropenia (FN) when the risk of FN was > 20%. However, these studies examined only one cycle of chemotherapy and did not account for costs of CSF in subsequent cycles, did not consider SP, and did not consider patients’ preferences. Methods: We conducted a cost-utility analysis to compare PP with SP in this setting using a Markov model for a time horizon of 8 cycles of chemotherapy with a government payer perspective. Costs were adjusted to 2006 $CAD. Ontario health economic data were used. The cost of hospitalization for FN was obtained from Ontario Case Costing Initiative. Data for efficacies of CSF, probabilities and utilities were obtained from published literature. Sensitivity analyses were conducted using a threshold of $100,000/QALY. Results: The base case costs for PP and SP were $22,077 and $17,641. The QALYs of PP and SP were 0.254 and 0.248. The incremental cost effectiveness ratio of PP to SP was $739,999/QALY. One-way sensitivity analyses showed that in order for PP to be cost-effective, the cost of hospitalization per episode of FN had to be > $31,138 (i.e. 2.5 times > base case), the cost of CSF per cycle had to be < $896 (base case = $1,960), the risk of FN in the 1st cycle had to be > 48% (base case = 24%), or the relative risk reduction of FN with CSF had to be > 97% (base case = 41%). Our result was robust to all other cost, probability and utility variables. First order microsimulation showed that < 17% of simulations were cost-effective. Conclusions: PP is not cost-effective when compared with SP for this population under most assumptions. PP only becomes attractive in places where the cost of hospitalization for FN is much more than that of Ontario, or the cost of CSF is under $896 per cycle. The costs of CSF and hospitalization in all cycles (instead of just one cycle) should be accounted for in any economic evaluation of CSF. Current guidelines recommending PP in this population should be revisited.

No significant financial relationships to disclose.
Barriers to cancer clinical trials (CCT) participation: “We have met the enemy and he is us.”
Authors: Comis R. L. , Colaizzi D. D. , Miller J. D.
Published: March 2020

6567

Background: A web based survey of attitudes and awareness of cancer survivors (Ca. surv) towards CCT was performed from 3–4, 2005. The survey was developed jointly by the Coalition of Cancer Cooperative Groups and Michigan State University (MSU) and executed by MSU and Knowledge Networks (KN). Methods: Ca surv. were obtained from a panel of 40,000 adults through KN based on a US household probablility sample who agree to weekly surveys in exchange for a free MSN box and ISP service. 2,029 panel members reported a cancer diagnosis (dx); 1,788/2,029 (88%) agreed to participate. Results: About 10% of Ca surv. are aware of CCT opportunities at the time of dx. 73% become aware through a physician (ASCO 2006: 6061). Ca surv. were asked to rank the most trusted sources of health care information from a list of 23 categories on a 0 (least) to 10 (most) scale. Physicians scored the highest (8.6) followed by information from the NCI (8.4) and reports from societies of cancer physicians/researchers (8.3). Although not significantly different from each other, all were significantly different from the other 20 sources (p<.05). CCT aware Ca surv. were asked whether the physician discouraged, was neutral or encouraged participation or made a little, moderate or great deal of effort to educate them and find a CCT. Enrollment (%) was directly related (p< 0.01) to the perceived physician involvement as follows: Encouragement: discouraged (0); neutral (16); encouraged (84); Educate: little (22); moderate (41%); great deal (64%); Find trial: little (23); moderate (39); great deal (82%). Of the 90% of Ca surv. who were not aware of CCT, 65% indicated that they would be somewhat or very receptive to enrollment if they had been made aware of an opportunity. Conclusion: Ca surv. are not CCT averse a priori. The physician is the most trusted, primary source of awareness and influence in decisions concerning CCT. Although there are myriad reported barriers to CCT participation, increased CCT participation hinges upon physician commitment and communication; conversely, a lack thereof may be the greatest barrier to increased CCT participation.

No significant financial relationships to disclose.
A review of 565 phase II trial abstracts from ASCO 2005: Design characteristics of contemporary trials evaluating cytotoxic versus non-cytotoxic regimens
Authors: Elser C. , Pond G. , Chen E. , Siu L.
Published: March 2020

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Background: New phase II trial designs have been proposed to accommodate the non-cytotoxic nature of molecularly targeted agents. In particular, the use of alternative endpoints and controls has been suggested. The objectives of this survey are to review the designs of contemporary phase II trials, to compare trials of cytotoxic versus non-cytotoxic regimens, and to identify predictors of acceptance for presentation. Methods: Abstracts of phase II trials of systemic anticancer therapy published in the 2005 ASCO Proceedings were hand searched. The trial context, type of intervention, trial design, endpoints, and completeness of reporting were assessed. Results: Our search yielded 565 abstracts: 72% were multi-center, 44% North American, 25% clearly identified as industry-sponsored, the median number of patients was 44 (range 8–346). Only 83% explicitly reported the study phase, 29% the primary endpoint, 11% the number of stages, and 5% the statistical design. For design properties, 16% used multiple arms and 6% used enrichment. Of trials reporting the primary endpoint, 48% used radiological or marker response and 22% time-to-event endpoints. The median number of endpoints was 4 (range 1–8). Non- cytotoxic regimens, which included targeted agents, hormone- or immunotherapy, constituted 22% of the trials reviewed, purely cytotoxic regimens 60%, the remaining 18% contained combinations of both. Trials of non-cytotoxic and combination regimens were more likely to report the primary endpoint (p=0.02), use time-to-event endpoints (p=0.006), have multiple arms, use enrichment, be conducted in North America, be industry-sponsored, and be accepted for oral or poster presentation (all p<0.001). Other predictors of publication type in multivariate analysis were multi-centricity, higher number of patients, industry involvement, and being conducted in North America (all p<0.05). Conclusions: Design properties of contemporary phase II trials of non-cytotoxic agents differ from trials of cytotoxic chemotherapy, and are more likely to be accepted for presentation at ASCO. Proposed new trial designs start to be more widely adopted. Most abstracts incompletely report design properties.

No significant financial relationships to disclose.
Timeliness of breast cancer diagnosis and initiation of treatment in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP)
Authors: Richardson L. C. , Royalty J. , Howe W. , Helsel W. , Kammerer W. , Benard V. B.
Published: March 2020

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Background: To examine intervals between breast cancer screening, diagnosis, and treatment initiation among low income and uninsured women in the National Breast and Cervical Cancer Early Detection Program during two time periods. Methods: We examined diagnostic and treatment intervals for the time periods of 1996–2000 and 2001–2005 to evaluate program progress. The intervals were defined as: (1) time between mammography and final diagnosis for all women receiving an abnormal mammogram result (including suspicious abnormality (SA), highly suspicious for malignancy (HSM) and assessment is incomplete (AI)) or abnormal clinical breast exam and; (2) time between diagnosis and treatment initiation among those diagnosed with cancer. Covariates including mammography result, age at screening, race/ethnicity, and metropolitan/urban/rural classification of residence were included in the analysis. Results: For the entire study period, 369,557 women screened for breast cancer through the NBCCEDP had abnormal screen results. For 1996–2000 and 2001–2005 time periods, the median interval to diagnosis after screening was 25 days and 23 days respectively. For those 22,302 women found to have cancer, the median interval from diagnosis to treatment increased from 12 days in the first time period to 14 days in the later time period. Overall, time to diagnosis improved from 1996–2000 compared to 2001–2005. However, time to treatment initiation was slightly longer (median increased by 2–3 days). Using data from the most recent period of 2001–2005, 93% of women with cancer initiated treatment within 120 days of screening. Conclusions: The goal of the NBCCEDP is to assure that women receive timely, quality breast cancer screening and diagnostic services and initiate treatment. Our data show that the program is meeting these goals. Disparities in breast cancer incidence, mortality and survival should diminish once all women have access to breast cancer early detection and treatment services.

No significant financial relationships to disclose.
Patient attitudes regarding payment for participation in a phase I cancer clinical trial
Authors: Gibbs A. , Merz J. F. , Gore L. , O'Bryant C. L.
Published: March 2020

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Background: Research industry practice reimburses healthy phase 1 study subjects and yet cancer patients who participate in a phase 1 study are rarely reimbursed. The ethical problems of disproportionate risk/benefit ratio and coercive informed consent are cited as reasons for not paying cancer study subjects. The purpose of this study is to determine if payment to participate in a phase 1 clinical trial affects a cancer subject's willingness to participate (WTP) in a clinical trial and to determine if any payment would reduce the therapeutic misconception. Methods: Eligible adults had consented to participate in a phase 1 clinical trial of an investigational drug at UCCC but had not yet initiated treatment. Subjects were identified by UCCC staff, consented to participate in this study, and then administered a questionnaire by phone. Primary analyses were descriptive in nature. Results: Thirty subjects were enrolled. The median age was 57 years (range 30–76); 53% were female; 97% were Caucasian; 77% had at least some college education; 47% had an annual household income of < $50,000. When asked an open-ended question, 53% of subjects stated that the main purpose of the phase 1 trial in which they consented to participate was efficacy. The majority of subjects (80%) did not think they should be paid to participate in a phase 1 cancer trial. Most subjects (73%) expected to benefit from phase I study participation and greater than 80% of subjects stated that payment would not change their perception or hope of benefit. There was a minor trend towards increased WTP with increased reimbursement or payment. Thirty-seven percent of subjects acknowledged that payment might affect what side effects they report. Conclusions: While payment appeared to have little or no affect on a cancer subject's expectation of benefit from a phase 1 trial, WTP increased slightly with increasing payment. Given these results, it seems that payment would not reduce the therapeutic misconception related to participation in phase 1 cancer trials. This study should be expanded to confirm these findings.

No significant financial relationships to disclose.
Cost-utility of adjuvant trastuzumab in Her-2/neu positive breast cancer: A Canadian perspective
Authors: Skedgel C. , Rayson D. , Younis T.
Published: March 2020

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Background: Recent RCTs have demonstrated a significant disease-free and overall survival advantage with adjuvant trastuzumab (aTZ) compared to chemotherapy alone in women with Her2/neu positive breast cancer. However, as aTZ is also associated with considerable costs and an increased risk of cardiotoxicity, an economic evaluation was undertaken to estimate the cost-utility (CU) of aTZ in terms of cost per quality-adjusted life year (QALY) gained relative to chemotherapy alone. Methods: A Markov model was developed to calculate the incremental costs and outcomes of 12 months of aTZ following chemotherapy in a hypothetical cohort of 1,000 women with Her2/neu positive breast cancer over a lifetime horizon. The model consisted of four broad health states: 1) disease-free, 2) local recurrence, 3) distant recurrence and 4) death. Each survival state was stratified as experienced with or without cardiotoxicity. The baseline rate of recurrence, the hazard ratio (HR) of recurrence with aTZ and the rate of adverse cardiac events were taken from recent RCTs. Age-sex specific background mortality, based on Statistics Canada life tables, was also incorporated. The cost of aTZ was based on our previous cost study (Drucker et al, ASCO 2006). Costs of local and distant cancer recurrence were derived from the literature, with an adjustment for the cost of palliative TZ (Potvin et al, ASCO 2005). Utility weights were taken from the literature. The model took a direct payer perspective, with costs reported in 2006 Canadian dollars (CDN$). Costs and QALYs were both discounted by 3% annually. The primary analysis assumed 5 years of benefit with aTZ therapy and an HR=1.0 over the remainder of the horizon. Results: Per 1,000 treated patients, aTZ was associated with a lifetime gain of 1,267 QALYs and an incremental cost of CDN$38.8 million. Lifetime CU was CDN$30,630 per QALY gained. aTZ met a CDN$50,000/QALY threshold at year 17. CU results were particularly sensitive to changes in the analysis horizon and assumptions regarding the long-term HR of aTZ. Conclusions: The lifetime CU of aTZ appears reasonable. However, further clinical follow-up is required to clarify the long-term outcomes of aTZ and confirm these CU estimates.

No significant financial relationships to disclose.