Yousuf Zafar

Improving the Methodologic and Ethical Validity of Best Supportive Care Studies in Oncology: Lessons From a Systematic Review

PURPOSE To systematically review the best supportive care (BSC) literature and to evaluate the ethical and methodologic validity issues by using widely acknowledged criteria. METHODS Two search strings that included both cancer and supportive as terms (with random article type, or review or meta-analysis) explored databases from 1966 to 2008. Citations, abstracts, and papers were reviewed for inclusion criteria, and relevant data were extracted by two independent researchers. Data were validated for accuracy. Ethical and methodologic validity were evaluated by using the criteria derived from the Helsinki Requirements of the WMA; CONSORT statements for the evaluation of reports of randomized, controlled trials; and the universal requirements for ethical clinical research. RESULTS Forty-three published papers were identified that described 32 studies, 20 of which incorporated the design of treatment plus supportive care (SC) versus SC alone, and 12 of which incorporated the design of treatment versus SC. Most of the studies had poor compliance to critical Helsinki requirements, to methodologic precautions derived from the CONSORT statement for studies involving a nonpharmacologic arm, and to four of seven universal requirements for ethical clinical research. CONCLUSION Lack of rigor in BSC studies has contributed to a generation of research with widespread ethical and methodologic shortcomings. Ad hoc SC and lack of standardization of SC delivery may be sources of systematic bias or error in BSC trials. Rectifying these shortcomings in future studies demands greater vigilance toward these issues by researchers, institutional review boards, editors, and peer reviewers. Given the prevalence of overlooked problems that are later identified, currently open BSC studies should be reevaluated by institutional review boards and researchers to check for ethical and methodologic validity, and identified shortcomings should be addressed.

Coping with cancer treatment-related financial burden.

161 Background: Growing evidence suggests that financial distress is a side effect of cancer care needing attention. Little is known about how patients cope with treatment-related financial distress. This study describes how patients with cancer cope with treatment-related costs and identifies those at greatest risk for using potentially harmful cost-coping strategies. METHODS Eligible patients for this cross-sectional, survey study were adults being treated for solid malignancies enrolled June 2010 to May 2011 in a national copay assistance program. Coping strategies were grouped as lifestyle-altering or care-altering. Descriptive statistics and analysis of variance assessed coping strategies and relationships between covariates. RESULTS Among 174 participants, 89% used at least one lifestyle-altering strategy to cope with costs, while 39% used a care-altering strategy. Most common care-altering coping strategies included: not filling a prescription (28%); and taking less medication than prescribed (23%). Lifestyle-altering strategies included: spending less on leisure activities (77%); spending less on basics (57%); borrowing money (54%); and spending savings (50%). The mean number of coping strategies was higher for patients < 65 than for those ≥ 65 (Table). Lower-income patients used more care-altering strategies than higher-income patients. Patients with more education and shorter duration of chemotherapy adopted more lifestyle-altering strategies than their counterparts. CONCLUSIONS Patients were generally more likely to use lifestyle-altering approaches to cope with treatment-related financial burden, but more than one-third adopted care-altering strategies. Younger patients and those with lower incomes were more likely to alter their care. Screening for and anticipating potentially harmful cost-coping behavior in the oncology clinic is important to reduce patient distress and promote optimal care. [Table: see text].

Developing a virtual collaborative to facilitate palliative care and quality improvement learning in oncology.

252 Background: Despite a strong evidence base and increasing calls for integration, oncologists find it difficult to deliver primary palliative care concurrent with standard oncology care. Solutions that promote practical integration of palliative care in oncology are needed. In an AHRQ-funded pilot, ASCO and the American Academy of Hospice and Palliative Medicine are developing the Virtual Learning Collaborative (VLC) to develop and test a scalable model for quality improvement and dissemination of best practices in palliative care within the oncology setting. METHODS The VLC will be a web-based learning and collaboration system built upon existing ASCO technology resources. We will select at least 25 oncology practices to participate in regular, facilitated learning sessions, collaborative discussions, and sharing of best practices. The VLC will equip each practice with the knowledge, tools, and coaching to select, test, and adopt a quality improvement intervention relevant to their own palliative care needs. Development of the VLC is ongoing; oncology practices begin participation in Spring 2014. RESULTS We will assess the VLC using protocol-driven evaluation methods common to technology development, quality improvement, implementation science, and educational initiatives. VLC usability, feasibility, and acceptability will be assessed through surveys of participating practices and focus groups. Longitudinal changes in conformance to palliative care metrics will be assessed using ASCOs Quality Oncology Practice Initiative (QOPI) system. We will use mixed qualitative and quantitative evaluation methods to assess ongoing changes in clinician knowledge and self-efficacy in applying palliative care principles. CONCLUSIONS We aim to develop and test a novel method for facilitating quality improvement and palliative care learning in oncology. Through this pilot, we will refine the VLC for implementation in the greater oncology community. Ultimately, this effort supports other ASCO and AAHPM quality improvement initiatives focused on clinician education and dissemination of best practices.

Feasibility of cancer clinical trial enrollment goals based on cancer incidence.

20Background: More than 20% of US clinical trials fail to accrue sufficient patients and terminate prematurely, impeding innovation and negating the valuable contributions of participating patients. The aim of this study is to estimate availability of patients for each trial opening in the national oncology clinical research portfolio to provide a benchmark for better understanding feasibility of clinical trial enrollment goals. Methods: The Database for Aggregate Analysis of ClinicalTrials.gov, up-to-date as of September 3, 2017, was used to identify actively-recruiting, interventional oncology trials at US sites. Observational studies were excluded as not all are registered. Trials were categorized via Medical Subject Headings or free text condition terms and sorted by cancer diagnosis. Trial slot availability was estimated between September 1, 2017, to August 31, 2018. Availability was estimated from total anticipated enrollment, assuming a constant recruitment rate. Estimates for studies with both for...

Validation and quality assessment of the Kilimanjaro Cancer Registry.

266 Background: The global cancer burden has increasingly shifted to low and middle-income countries and is particularly pronounced in Africa. However, there remains a lack of comprehensive information about cancer incidence due to limited development of cancer registries. In Moshi, Tanzania, a regional cancer registry exists at Kilimanjaro Christian Medical Center (KCR). The quality of the registry data is unknown. Our objective was to evaluate the completeness and quality of the KCR. METHODS In October 2015 we conducted a retrospective review, validating internal consistency of registry records compared with paper-based medical and pathology records. We randomly sampled approximately 3% of over 3000 registry cases (n = 100), focused on cases abstracted from 2014-15. Four independent reviewers not associated with the KCR manually collected and compared key data elements (e.g., cancer site, morphology, diagnosis date). Data were collected using Microsoft Excel. Data management and analysis were conducted in Stata. RESULTS The KCR contains information on over 3000 patients from 32 tribal groups and 8 geographic areas in the Kilimanjaro region. All of the 100 reviewed cases had complete cancer site and morphology in the registry. Six had a recorded stage. For the majority of cases (n = 92) the basis of diagnosis was pathology. Pathology records were found in the medical record for 41% of cases; for the remainder, pathology records were stored separately in the pathology department. Of sampled cases, the KCR and medical records were 98% and 94% concordant for primary cancer site and morphology, respectively. For 28% of cases, recorded diagnosis dates were within 14 days of what was found in the medical record, and for 32% of cases they were within 30 days. CONCLUSIONS Although training is needed to standardize diagnosis date definitions, this study suggests that KCR data is high quality. Research is needed to determine effectiveness at ascertaining all patients in its catchment area. The registry may have utility for resource planning and research purposes.

Symptom burden, health-related quality of life, and treatment preference over time as reported by patients with metastatic colorectal cancer (mCRC).

82 Background: Clinicians have difficulty predicting longitudinal changes in patient symptom burden and quality of life, and then how those changes might affect treatment preference. The primary aim of this pilot study was to investigate how self-reported symptom burden, quality of life, and treatment preference change over time in mCRC patients with limited life expectancy. METHODS Eligible mCRC patients had incurable disease, received chemotherapy at Duke or Duke Raleigh, were > = 18 years old, and spoke English. Patients were surveyed at each clinic visit and followed for up to 3.8 years on study. Measures included FACT-C (Functional Assessment of Cancer Therapy-Colorectal), PCM (Patient Care Monitor; a validated, 87-item review of systems survey; items measured on a 0-10 scale), and QQQ (Quality-Quantity Questionnaire; a validated, 8-item measure of cancer patient preference for quantity vs. quality of life; items measured on a 1-5 Likert scale). Demographic, disease, and treatment data were abstracted from the medical record. RESULTS The 56 patients were primarily male (68%) and Caucasian (79%) with a mean age of 55 at diagnosis of metastatic disease. Patients answered surveys a mean of 6.8 times each, with a median 364 days between first and last surveys. Over time, patients reported most symptoms improved or stayed the same (72%, n = 63 symptoms). Mean symptom scores that improved the most from first to last survey were fatigue (3.92 to 3.03) and nausea (2.1 to 1.4), while pain (1.9 to 2.5) and cough (0.4 to 0.7) worsened the most. Decision making about treatment preference also did not change over time, with mean QQQ scores from first survey (22, n = 28) to last survey (22, n = 16) remaining stable. Mean QQQ length and quality scores likewise were unchanged (12.9 to 12.8; 12.4 to 12.2 respectively). CONCLUSIONS In this pilot study of mCRC patients with limited life expectancy, reported symptom burden scores remained stable or modestly improved over time, while preferences for quality vs. quantity of life remained stable. These findings suggest that patients with advanced cancer might perceive symptom burden differently over the course of their treatment.

A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC).

68 Background: EC is commonly managed with concurrent chemoradiotherapy, with or without surgical resection. The optimal combination and dose of agents is the subject of continued investigation. This study examines chemotherapeutic agents with known efficacy in EC in combination with the EGFR inhibitor panitumumab. Methods: Eligible pts received RT (1.8 Gy qd to 50.4 Gy) combined with concurrent chemotherapy. Dose-level (DL) 1 was cape (625 mg/m2/bid RT days), ox (40 mg/m2 weekly X 6 weeks), and pmab (3.6 mg/kg, weeks 1, 3 and 5). Chemotherapy doses were escalated barring dose limiting toxicity (DLT). The primary endpoint was defining the maximally tolerated dose with this combination. Secondary endpoints included toxicity and radiographic/pathologic response rates. Results: Twenty-nine pts were enrolled. Twenty-five had adenocarcinoma, 24 (83%) were cN+ and 9 (31%) had M1a/b disease. DLT was not encountered in DL 1. Two of 6 patients at DL 2 (cape 825 mg/m2/bid RT days, ox 50 mg/m2 weekly, pmab 4.8 mg/kg...

Copayment assistance and adherence to prescription medication among patients with cancer.

57 Background: The relationship between prescription medication adherence and copay assistance is understudied and directly impacts quality of care. METHODS We conducted a cross-sectional survey study assessing patient-reported failure to take medication as prescribed (nonadherence) and application for copay assistance. Participants were enrolled between 6/2010-5/2011 from the HealthWell Foundation (a copay assistance program) and Duke Cancer Center. Eligible patients were adults receiving treatment for a solid malignancy. Nonadherence was defined as taking a less than prescribed amount of medication, not filling or partially filling a prescription, or taking medications prescribed for someone else. Adherence and receipt of copay assistance were not linked to a specific drug. Logistic regression assessed the association between medication nonadherence, copay assistance application, and financial burden. RESULTS Among 258 participants, 75% applied for copay assistance. 38% (n=99) reported nonadherence with medications due to cost. Compared to adherent participants, nonadherent participants were more likely to: ask their doctor for a less expensive medication than prescribed (p<0.001); reduce spending on basics like food or clothing to pay for medication (p<0.001); purchase an over-the-counter drug to replace a more costly prescription (p<0.001); borrow/use credit to pay for medications (p<0.001); and talk with doctors about treatment-related costs (p=0.014). In adjusted analyses applying for copay assistance did not change odds of nonadherence. Having a prescription drug plan (OR 6.56, 95% CI 1.69-25.53) and utilizing coping strategies (OR 2.72, 95% CI 2.03-3.65) increased odds of nonadherence; older age (OR 0.93, 95% 0.88-0.98) decreased odds of nonadherence. CONCLUSIONS Medication nonadherence due to cost was prevalent among cancer patients whether or not they applied for copay assistance. To afford medications cancer patients adapted their lifestyles and altered their care. Future research should investigate whether underinsured patients have timely access to copay assistance programs and whether copay assistance impacts the quality of care.