Innovation in Healthcare Delivery: Commentary on an Evolutionary Approach.

Zwarenstein (2015) proposes a novel approach to healthcare innovation that parallels biological evolution, based on stimulation and reward of multiple small competing innovation projects conducted in the field by decentralized teams. Projects would be designed with explicit outcome targets and results would be widely disseminated and publicly available. More successful projects would be grown and spread. Critical to the model is accepting and reporting failure as well as success, for the benefit of future project design. Examining biological evolution for lessons for healthcare delivery innovation illuminates the need for diversity among healthcare systems to achieve optimum application of best practice interventions across jurisdictions with differing population, provider and facility characteristics. However, careful coordination will be needed to achieve the balance between diversity and harmony across jurisdictions necessary for effective governance and interaction. There are important methodological issues to be addressed to reduce the uncertainty inherent in comparisons of results among discrete innovation projects, especially when observed improvements over the baseline are modest. As well as evolutionary improvement in healthcare outcomes, the model should progressively increase decentralized capacity and expertise in innovation processes.

Adjuvant therapy with the monoclonal antibody Edrecolomab plus fluorouracil-based therapy does not improve overall survival of patients with stage III colon cancer.

PURPOSE: Edrecolomab (ED) is a murine monoclonal antibody targeting the EpCam antigen. This phase III randomized multicenter trial investigated the benefit of adding ED to fluorouracil (FU) based therapy in patients with stage III colorectal cancer. PATIENTS AND METHODS: Patients with stage III colon cancer were randomly assigned to one of two treatments after curative surgery. Patients in arm 1 received five infusions of ED together with FU-based chemotherapy; patients in arm 2 received FU-based chemotherapy alone. The primary end point was overall survival (OS). RESULTS: One thousand eight hundred thirty-nine patients were randomly assigned; results were analyzed on an intent-to-treat basis. Patient characteristics were well-balanced across treatment arms. Five-year follow-up has been completed. Patients randomly assigned to ED plus FU-based therapy showed a 5-year survival rate of 69.6% while for patients receiving FU-based therapy, the rate was 68.2%. The hazard ratio for death with ED plus FU-based therapy compared to FU-based therapy was 0.896 (95% CI, 0.752 to 1.068), which was not statistically significant (P = .220). The adverse effect profiles of the two treatment arms were similar, with the main adverse effects being diarrhea, abdominal pain, and nausea. Anaphylaxis occurred in fewer than 1% of patients receiving ED. CONCLUSION: For patients with stage III colon cancer, the addition of ED to FU-based therapy had no statistically significant effect on OS.

Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials.

PURPOSE: Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. PATIENTS AND METHODS: After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m(2) administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m(2) [FFCD] x 5 days or FU 370 mg/m(2) plus l-leucovorin 100 mg/m(2) IV x 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm). RESULTS: A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis. CONCLUSION: This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus-based regimen after complete resection of colorectal cancer metastases.

Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803.

PURPOSE: Randomized studies have shown that irinotecan (CPT-11) extends survival in metastatic colorectal cancer patients when administered in second-line and when added to fluorouracil (FU) plus leucovorin (LV) in first-line therapy of metastatic colorectal cancer. When this study was initiated, FU plus LV was standard adjuvant treatment for stage III colon cancer. We evaluated the efficacy and safety of weekly bolus CPT-11 plus FU plus LV in the treatment of patients with completely resected stage III colon cancer. METHODS: A total of 1,264 patients were randomly assigned to receive either standard weekly bolus FU plus LV regimen or weekly bolus CPT-11 plus FU plus LV. The primary end points of the study were overall survival (OS) and disease-free survival (DFS). RESULTS: Treatment arms were well-balanced for patient characteristics and prognostic variables. There were no differences in either DFS or OS between the two treatment arms. Toxicity, including lethal toxicity, was significantly higher on the CPT-11 plus FU plus LV arm. CONCLUSION: The addition of CPT-11 to weekly bolus FU plus LV did not result in improvement in DFS or OS in stage III disease, but did increase both lethal and nonlethal toxicity. This trial demonstrates that advances in the treatment of metastatic disease do not necessarily translate into advances in adjuvant treatment, and it reinforces the need for randomized controlled adjuvant studies.

A longitudinal study of exercise barriers in colorectal cancer survivors participating in a randomized controlled trial.

BACKGROUND: The Colorectal Cancer and Home-Based Physical Exercise (CAN-HOPE) trial compared the effects of a 16-week home-based exercise program to usual care on quality of life in colorectal cancer survivors. PURPOSE: In this study, we report the weekly exercise barriers from the exercise group. METHODS: Participants randomized to the exercise group (N = 69) were asked to report their exercise on a weekly basis by telephone. Those participants not achieving the minimum weekly exercise prescription (3 times per week of 30 min of moderate intensity exercise) were asked for a primary exercise barrier. RESULTS: We obtained 1,073 (97.2%) weeks of adherence data out of a possible 1,104 (i.e., 69 x 16). Participants did not meet the minimum exercise prescription in 39.2% (421/1,073) of the weeks. We obtained an exercise barrier in 83.8% (353/421) of these cases. Overall, participants reported 37 different exercise barriers; the three most common were lack of time/too busy, nonspecific treatment side effects, and fatigue. The top 7 to 10 barriers accounted for 70% to 80% of all missed exercise weeks. CONCLUSIONS: These findings may have utility for promoting exercise in this population both inside and outside of clinical trials.

Predictors of adherence and contamination in a randomized trial of exercise in colorectal cancer survivors.

The purpose of this study was to examine predictors of exercise adherence (i.e. exercise in the intervention group) and exercise contamination (i.e. exercise in the control group) in a randomized controlled trial of home-based exercise in colorectal cancer survivors. At baseline, 102 participants completed measures of the theory of planned behavior, personality, past exercise, exercise stage of change, physical fitness, and medical/demographics and then were randomly assigned in a 2:1 ratio to an exercise (n=69) or control (n=33) group. Exercise was monitored weekly for 16 weeks using self-reports by telephone. Ninety-three (91%) participants completed the trial. Adherence was 76% in the exercise group and contamination was 52% in the control group. Hierarchical stepwise regression analyses indicated that baseline exercise stage of change (beta=0.35; p=0.001), employment status (beta=-0.28; p=0.010), treatment protocol (beta=-0.26; p=0.018), and perceived behavioral control (beta=0.20; p=0.055) explained 39.6% of the variance in exercise adherence. Intentions (beta=0.36; p=0.049) and baseline exercise stage of change (beta=0.30; p=0.095) explained 29.9% of the variance in exercise contamination. These findings may have implications for conducting clinical trials of exercise in colorectal cancer survivors and for promoting exercise to colorectal cancer survivors outside of clinical trials.

A retrospective study on the use of post-operative colonoscopy following potentially curative surgery for colorectal cancer in a Canadian province.

BACKGROUND: Surveillance colonoscopy is commonly recommended following potentially curative surgery for colorectal cancer. We determined factors associated with patients undergoing a least one colonoscopy within five years of surgery. METHODS: In this historical cohort study, data on 3918 patients age 30 years or older residing in Alberta, Canada, who had undergone a potentially curative surgical resection for local or regional stage colorectal cancer between 1983 and 1995 were obtained from the provincial cancer registry, ministry of health and cancer clinic charts. Kaplan-Meier estimates of the probability of undergoing a post-operative colonoscopy were calculated for patient, tumor and treatment-related variables of interest. RESULTS: A colonoscopy was performed within five years of surgery in 1979 patients. The probability of undergoing a colonoscopy for those diagnosed in the 1990s was greater than for those diagnosed earlier (0.65 vs 0.55, P < 0.0001). The majority of the difference was seen at one-year following surgery, consistent with changes in surveillance practices. Those most likely to undergo a colonoscopy were those under age 70 (0.74 vs 0.50 for those age 70-79, P < 0.0001), who underwent a pre-operative colonoscopy (0.69 vs 0.54, P < 0.0001), and who underwent a resection with reanastomosis (0.62 vs 0.47 for abdominoperineal resection, P < 0.0001) by a surgeon who performs colonoscopies (0.68 vs 0.54, P < 0.0001). CONCLUSIONS: The majority of patients undergo colonoscopy following colorectal cancer surgery. However, there are important variations in surveillance practices across different patient and treatment characteristics.

Systematic review of management of colorectal cancer in elderly patients.

This study is designed to clarify the benefits and risks of chemotherapy and radiation therapy in elderly patients with colorectal cancer through a systematic review of the literature. Searches of the Medline, Embase, and Cochrane Library databases; PDQ Cancer Information Summaries, American Society of Clinical Oncology Guidelines, Cancer Care Ontario Practice Guideline Initiative, Interprovincial Drug Strategies and Guidelines Group, and OncoLink Web sites; and manual searches of meeting proceedings and bibliographies were performed. Additional studies known to the authors were also identified. Randomized controlled trials, reviews, and guidelines evaluating the impact of age on overall survival and/or toxicity with adjuvant and palliative therapies for colorectal adenocarcinoma were selected. A preset study selection form was applied to all identified studies. All selected studies underwent a preset study appraisal. Analyses of the effect of age on overall survival benefits and/or toxicity of therapy were extracted. A qualitative synthesis and narrative review was undertaken. There is good evidence to support that patients = 80 years of age have similar overall survival benefits with adjuvant 5-fluorouracil (5-FU)-based chemotherapy for colon cancer and with palliative first-line monotherapy for metastatic colorectal cancer, as do younger patients. Data are limited with regard to toxicity of therapy in older patients in these settings. An increase in toxicity with bolus 5-FU chemotherapy regimens is evident. There is a paucity of data regarding adjuvant treatment of older patients with rectal cancer. More elderly patients need to be enrolled in clinical trials in order to fully evaluate the outcomes of colorectal cancer therapy in this population. Further studies are warranted.