Challenges in knowledge translation: the early years of Cancer Care Ontario's Program in Evidence-Based Care.

BACKGROUND: Cancer Care Ontario's Program in Evidence-Based Care (pebc) was formalized in 1997 to produce clinical practice guidelines for cancer management for the Province of Ontario. At the time, the gap between guideline development and implementation was beginning to be acknowledged. The Program implemented strategies to promote use of guidelines. METHODS: The program had to overcome numerous social challenges to survive. Prospective strategies useful to practitioners-including participation, transparent communication, a methodological vision, and methodology skills development offerings-were used to create a culture of research-informed oncology practice within a broad community of practitioners.Reactive strategies ensured the survival of the program in the early years, when some within the influential academic community and among decision-makers were skeptical about the feasibility of a rigorous methodologic approach meeting the fast turnaround times necessary for policy. RESULTS: The paper details the pebc strategies within the context of what was known about knowledge translation (kt) at the time, and it tries to identify key success factors. CONCLUSIONS: Many of the barriers faced in the implementation of kt-and the strategies for overcoming them-are unavailable in the public domain because the relevant reporting does not fit the traditional paradigm for publication. Telling the "stories behind the story" should be encouraged to enhance the practice of kt beyond the science.

Use of systemic therapy in women with recurrent ovarian cancer--development of a national clinical practice guideline.

OBJECTIVE: To develop a guidance document concerning the use of systemic therapy for women with recurrent ovarian cancer that would be applicable for the Canadian health care system. This will be done using a standardized systematic review process, guideline evaluation instruments, multi-disciplinary expert consensus opinion and evidence-rating systems. DATA SELECTION: The primary data sources were MEDLINE, National Guideline Clearinghouse and Cochrane Library. METHODS: Clinical practice guidelines, technology assessments, systematic reviews and randomized controlled trials addressing systemic therapy for women with recurrent ovarian cancer were eligible. DATA EXTRACTION: Data was identified and extracted by the methodology team and reviewed by the authors. Results were reviewed and discussed by members of an expert working group comprised of a multidisciplinary and geographic divergent group of practitioners. DATA SYNTHESIS: The existing 7 practice guidelines underwent formal evaluation for quality, currency and content using the AGREE tool. Recommendations with evidence-ratings were developed. This data was used by a pan-Canadian panel in an informal consensus process, which resulted in the initial draft of a guideline. The guideline team reviewed the draft and made further edits to ensure the guideline's appropriateness for a national context. Practitioner feedback was requested from 165 health care providers who treat ovarian cancer from across Canada. Overall response rate was 37% and was very positive. Comments were reviewed and the guideline was edited appropriately. CONCLUSION: The development of a national practice guideline on the use of systemic therapy for recurrent ovarian cancer was feasible using systematic literature review, expert consensus, guideline evaluation instruments, evidence-rating systems, independent internal and external review measures and final approval by a national discipline specific society (GOC). Recommendations for practice are offered.

Promoting best gynecologic oncology practice: a role for the Society of Gynecologic Oncologists of Canada.

During March 30-April 1, 2005, the Society of Gynecologic Oncologists of Canada (GOC) and the Canadian Strategy for Cancer Control (CSCC) Clinical Practice Guidelines Action Group (CPG-AG) met to determine how GOC would like to influence practice in the care of women with gynecologic cancer.explore a collaborative model for developing and implementing evidence-based practice guidelines.investigate the utility of the cpg evaluation and adaptation cycle as a tool for selecting, adapting, and adopting guidelines.At the workshop meeting, 21 members of the GOC and the cpg-ag heard presentations from various Canadian guideline initiatives. As an example of adaptation and adoption processes, the AGREE (Appraisal of Guidelines for Research and Evaluation) tool was applied to guidelines in recurrent ovarian cancer, and the group explored their opportunity to use knowledge translation to influence the care of women with gynecologic cancer.The themes influencing practice are consistent with GOC's mandate. The future is expected to involve partnering with other groups to maximize scarce resources. Resources should be directed to facilitating implementation of existing guidelines rather than to developing new documents. The full spectrum of cancer care includes prevention, screening, diagnosis, primary treatment, follow-up, treatment of recurrent disease, and palliation. High-quality evidence is available in some areas, but gaps exist where guideline panels could provide guidance. Development of a pan-Canadian gynecologic oncology process could provide an opportunity to influence access to care at the political and policy levels.The GOC will develop linkages such that the toolbox available through CSCC-CPG-AG can be incorporated into future collaboration.

International assessment of the quality of clinical practice guidelines in oncology using the Appraisal of Guidelines and Research and Evaluation Instrument.

PURPOSE: To describe the quality of oncology guidelines developed in different countries. METHODS: The Appraisal of Guidelines and Research and Evaluation (AGREE) Instrument was used to assess the quality of 100 guidelines (including 32 oncology guidelines) from 13 countries. The criteria of the instrument are grouped into six quality domains: scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, and editorial independence. RESULTS: Oncology guidelines had significantly higher scores on rigor of development than nononcology guidelines (42.2% v 29.4%; P =.02). In particular, systematic methods to search for evidence were more often used (P =.01); the methods for formulating the recommendations were more clearly described (P =.02); and health benefits, risks, and side effects were more often considered in formulating the recommendations (P =.03). Although the standardized scores for the other domains were not significantly different, the oncology guidelines had significantly higher scores for items measuring inclusion of all relevant professional groups (P =.05), consideration of patient views (P =.04), and presentation of different options (P =.05). Only three organizations producing oncology guidelines had standardized scores more than 60% for more than three domains. CONCLUSION: The quality of clinical practice guidelines (CPGs) is modest in general, but for certain domains, oncology guidelines seem to be of better quality than others. The experience of the organization may explain higher scores for some items. Research projects and training aimed at improving the quality of guidelines should be developed. The AGREE instrument could provide a basis for defining steps in a shared development approach to produce high-quality CPGs.

Concurrent cisplatin-based chemotherapy plus radiotherapy for cervical cancer--a meta-analysis.

PURPOSE: To evaluate the role of concurrent cisplatin plus radiotherapy in the treatment of cervical cancer. METHODS: A systematic review of randomized trials of cisplatin administered concurrently with external beam radiotherapy versus radiotherapy without cisplatin for cervical cancer was combined with a meta-analysis of results abstracted from published reports of the trials. RESULTS: Pooled survival rates from eight randomized trials that evaluated the role of cisplatin, alone or in combination with other chemotherapy agents, administered concurrently with external beam radiotherapy to patients with cervical cancer demonstrated a statistically significant effect in favour of cisplatin-based chemotherapy plus radiotherapy compared with radiotherapy without cisplatin (relative risk [RR] of death, 0.74; 95% confidence interval [CI], 0.64 to 0.86). The pooled RR of death among the six trials that enrolled only women with locally advanced cervical cancer was 0.78 (95% CI, 0.67 to 0.90). The pooled relative risk for the two trials in high-risk early-stage disease also demonstrated a statistically significant benefit for the addition of cisplatin-based chemotherapy to radiotherapy (RR=0.56; 95% CI, 0.41 to 0.77). CONCLUSION: This meta-analysis confirms that treatment with concurrent cisplatin-based chemotherapy plus radiotherapy improves overall survival over various controls in women with locally advanced cervical cancer, large stage IB tumours (prior to surgery) and high-risk early-stage disease (following surgery). The variation in control treatments and the quality of their delivery among the randomized trials makes interpretation difficult. Nonetheless, the meta-analysis supports the use of concurrent cisplatin with radical radiotherapy in the treatment of cervical cancer.

A controlled "before-after" study: impact of a clinical guidelines programme and regional cancer network organization on medical practice.

A regional cancer network has been set up in the Rhône-Alpes region in France. The aim of the project is to improve the quality of care and to rationalize prescriptions in the network. In this network, we assessed the impact of the implementation of a clinical practice guidelines project by assessing the conformity of practice with the guidelines and comparing this with the conformity in an external matched control group from another French region without a regional cancer network. Four hospitals (private and public) accepted to assess the impact of the clinical practice guidelines on the management of breast and colon cancer in the experimental group and three hospitals (private and public) in the control group. In 1994 and 1996, women with non-metastatic breast cancer (282 and 346 patients in the experimental group, 194 and 172 patients in the control group, respectively) and all new patients with colon cancer (95 and 94 patients in the experimental group, and 89 and 118 patients in the control group, respectively) were selected. A controlled "before-after" study, using institutional medical records of patients with breast and colon cancer. The medical decisions concerning the patients were analyzed to assess their compliance with the clinical practice guidelines. When medical decisions were judged to be non-compliant, we verified if they were based on scientific evidence in a published article, if they were not, the medical decision was classified as having "no convincing supporting scientific evidence". The compliance rates were significantly higher in 1996 than in 1994 in the experimental group; 36% (126 out of 346) vs 12% (34 out of 282) and 46% (56 out of 123) vs 14% (14 out of 103) (P<0.001) for breast and colon cancer, respectively. Whereas, in the control group the compliance rates were the same for the two periods; 7% (12 out of 173) vs 6% (12 out of 194) (P=0.46) and 39% (49 out of 126) vs 32% (31 out of 96), P=0.19. In the experimental group, in 1994, 101 of the 282 medical decisions (36%) and 27 of the 103 (26%) for breast and colon cancer, respectively, were classified as having "no convincing supporting scientific evidence" compare with 72 out of 346 in 1996 (21%) for breast cancer, and 21 of the 123 (17%) for colon cancer P<0.05. Whereas in the control group these results were 106 out of 194 in 1994 (55%) and 90 out of 172 in 1996 (52%), P=0.65 for breast cancer and 28 out of 96 in 1994 (29%) and 30 out of 126 in 1996 (24%), P=0.36 for colon cancer. The development and implementation strategy of the clinical practice guidelines programme for cancer management results in significant changes in medical practice in our cancer network. These results would suggest that introducing guidelines with specific implementation strategy might also increase the compliance rate with the guideline and "evidence-based medicine".

A National Cancer Institute of Canada clinical trials group phase II study of eniluracil (776C85) and oral 5-fluorouracil in patients with advanced squamous cell head and neck cancer.

UNLABELLED: BACKGROUND/PATIENTS AND METHODS: Thirty-two patients with recurrent head and neck cancer (HNC) following radiotherapy and/or surgery were treated with eniluracil (10 mg/m2) and 5-fluorouracil (5-FU) (1 mg/m2) (E5F) orally twice daily for 28 days followed by a seven-day treatment free period. Thirty-five-day cycles were repeated until disease progression, unacceptable toxicity or patient refusal. Doses were modified for toxicity. Standard toxicity and response criteria were used. RESULTS: Thirty-two patients were accrued; thirty-two and twenty-eight patients were evaluable for toxicity and response, respectively. Twelve patients received three or more cycles of E5F. Drug related toxicities were usually grade 1-2 intensity and included lethargy, nausea or diarrhea (> or = 25% of patients), and anorexia, rash or itch, stomatitis or vomiting (12%-24% of patients). Hematologic toxicity was generally mild; two patients experienced grade 3-5 leukopenia or thrombocytopenia. No significant biochemical toxicity was seen. One patient was withdrawn (severe nausea and vomiting) and one patient died because of drug related toxicity (thrombocytopenia). In the final analysis there were one complete and four partial responses for a 15.6% overall response. CONCLUSIONS: E5F demonstrates activity in chemotherapy naïve patients with advanced HNC cancer with acceptable toxicity profile. Further investigation of E5F with other active agents is warranted in HNC.

Funding new cancer drugs in Ontario: closing the loop in the practice guidelines development cycle.

PURPOSE: The previously described practice guidelines development cycle follows an iterative model in which recommendations are reached by a process that incorporates practitioners at all phases. A key feature is the separation of the evidence-based systematic review and the generation of recommendations from policy decisions surrounding implementation. This article describes how this implementation phase has evolved in Ontario and how implementation has affected the guidelines process. METHODS: The development of the New Drug Funding Program in Ontario and the appointment of a policy advisory committee (PAC) to make funding recommendations were reviewed. The decision-making framework of the PAC is described in this article. RESULTS: The PAC has had to address a number of issues in making funding recommendations. These issues have included dealing with evidence arising solely from phase II versus phase III trials, using economic information, and involving community representatives in its deliberations. Its activities have had a substantial impact on the practice guidelines initiative. CONCLUSION: It is possible to integrate an evidence-based, practitioner-driven approach to clinical guideline development with a funding program that takes policy considerations into account. However, even though these two roles are conceptually separate, the needs of the funding program have inevitably had an impact on the guidelines process.

Choosing a concomitant chemotherapy and radiotherapy regimen for squamous cell head and neck cancer: A systematic review of the published literature with subgroup analysis.

BACKGROUND: A systematic review was conducted to develop clinical recommendations for concomitant chemotherapy (CT) and radiotherapy (RT) in patients with locally advanced squamous cell head and neck cancer (SCHNC). METHODS: Results of published randomized controlled trials (RCTs) were pooled using Meta-analyst(0.988) software. RESULTS: A pooled analysis of 18 RCTs (20 comparisons) involving 3,192 patients detected a reduction in mortality for concomitant therapy compared with RT alone (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.52-0.74; relative risk, 0.83; risk reduction, 11%; p < .00001). Platinum-based regimens involving 1,514 patients from nine trials (10 comparisons) were most effective (OR, 0.57; 95% CI, 0.46-0.71; p < .00001; risk reduction, 12%). Concomitant therapy produced more acute adverse effects than RT alone. CONCLUSION: Platinum-based concomitant CT and RT is superior to conventional RT alone in improving survival in locally advanced SCHNC. Subgroup analyses can be used to help in choosing the most appropriate concomitant regimen.

Trends in hormonal management of prostate cancer: a population-based study in Ontario.

OBJECTIVE: To provide a population-based description of current practice in the use of hormonal management of prostate cancer. DESIGN,SETTING & PARTICIPANTS: All men in Ontario, Canada, age 65 and older, with confirmed prostate cancer starting maintained hormonal therapy, from July 1992 through December 1998 (11,435 patients). Data sources included the provincial drug benefit plan, hospital services data, and Ontario Cancer Registry. OUTCOME MEASURES: Rates and trends in the use of: surgical or medical castration; total androgen blockade (TAB); and monotherapies based on steroidal or nonsteroidal antiandrogens. RESULTS: In 5.5 years, use of 'standard' therapy based on surgical or medical castration alone dropped from 36% to 26% of patients, while the use of TAB doubled from 22% to 41%. Approximately 15% of patients received nonsteroidal antiandrogens without evidence of therapy aimed at central androgen blockade. Marked regional differences were observed and not explained by patient age or practitioner specialty. CONCLUSIONS: New hormonal therapies for prostate cancer have implications in terms of disease control, patient survival, side effects, and costs. Rapid growth in prescribing of antiandrogens may represent an unnecessary expense for public or private payers, and observed regional differences likely reflect lack of consensus on the relative merit of TAB. Patients and practitioners must have current information on the advantages and disadvantages of different therapeutic options, and quality-of life, particularly with respect to emerging drug therapies.

Prophylaxis of oral mucositis in irradiated head-and-neck cancer patients: a proposed classification scheme of interventions and meta-analysis of randomized controlled trials.

PURPOSE: To identify, classify, and evaluate agents used in the prophylaxis of oral mucositis in irradiated head and neck cancer patients. METHODS: Data sources included multiple databases and manual citation review of relevant literature. Based on the eligibility criteria, 59 studies were independently reviewed by two reviewers. Forty-two studies were included in the classification scheme, of which 15 met the criteria for inclusion in the meta-analysis. Data were extracted by duplicate independent review, with disagreement resolved by consensus. RESULTS: Overall, the interventions reduced the odds of developing severe oral mucositis, when assessed by clinicians, by 36% (OR: 0.64; 95% CI: 0.46, 0.88). Subgroup analysis suggested that only the narrow-spectrum antibacterial lozenges were effective (OR: 0.45; 95% CI: 0.23, 0.86); however, the power of the aggregated data in the other classes may have been insufficient to detect differences. When the outcome was assessed by patients, no significant difference was seen in the outcome between the treatment and the control groups (OR: 0.79; 95% CI: 0.56-1.12). CONCLUSIONS: Overall, interventions chosen on a sound biologic basis to prevent severe oral mucositis are effective. In particular, when oral mucositis is assessed by clinicians, narrow-spectrum antibiotic lozenges appear to be beneficial. Methodologic limitations were evident in many of the studies. Further research using validated measurement tools in larger, methodologically sound trials is warranted.

Development of clinical practice guidelines: surgical perspective.

Clinical practice guidelines (CPGs) are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. The implications of this definition are that: the methodologic perspective and operations for systematic development must be specified, a strategy is needed to account for the patient's perspective in the CPG development process and the clinical decision, and a mechanism is required to determine how appropriateness ought to be conceptualized and defined. Addressing these issues, we review models of CPG development, outline challenges to evidence-based approaches to CPG development, address unique factors relevant to the development of guidelines for the surgical community, introduce an Ontario practice guidelines strategy that uses complementary methods of CPG development, and summarize the feedback provided by the surgical community regarding the practice guidelines produced in Ontario's cancer system.

Essence of evidence-based medicine: A case report.

PURPOSE: To illustrate the complexities of the evidence-based approach in clinical oncology practice and the implications for guidelines and evaluation of processes of care. PATIENT AND METHODS: A case report is presented in which a limited systematic review of the literature was used to address a specific clinical problem in an individual patient. Experts' opinions were also sought. RESULTS: A reasonable clinical decision was made by a participating patient based on indirect evidence of benefit that would be insufficient to support the same decision as a health policy in some jurisdictions. CONCLUSION: The practice of evidence-based oncology requires clinical judgment about the validity and applicability of research evidence. The factors that influence an evidence-based decision in the clinical context differ from those in the broader policy context, which could lead to legitimate differences in recommendations based on the same information. Used properly, the individual case report can be a powerful tool to illustrate complex clinical decision phenomena.

Evidence-based paradigms and opinions in clinical management and cancer research.

Clinical management involves values, the recognition of a patient's unique circumstances, and information. Given strong biases in the way we all process experience, clinical decision making must acknowledge the results of formal research. Evidence-based clinical management requires that we take account of the whole body of available evidence, not a potentially biased "biopsy" of it. Systematic literature review is therefore a central element. Such an approach is time consuming and requires skills in literature search and data evaluation, which physicians frequently have not been taught. Computing and library facilities are an important aid, as is the development of evidence-based resources such as the Cochrane Library Collection. Practice guidelines can prove useful and acceptable to clinicians if they are both evidence- and practice-based. The largest single obstacle to evidence-based clinical management is the bias against the reporting of studies with negative findings. This can be overcome by compulsory trial registration.

Health care professionals' familiarity with non-pharmacological strategies for managing cancer pain.

Many studies have confirmed unnecessary suffering among cancer patients, due to the inadequate use of analgesic medication and other effective interventions. While pharmacological treatments are appropriately the central component of cancer pain management, the under-utilization of effective nonpharmacological strategies (NPS) may contribute to the problem of pain and suffering among cancer patients. The purpose of this study was to determine health care professionals' familiarity with, and perceptions regarding, NPS for managing cancer pain, and to assess their interest in learning more about NPS as adjuncts to pharmacological analgesics. Two-hundred and fourteen health care professionals were surveyed at two cancer treatment centres in Ontario, Canada. The self-report questionnaire included questions regarding 11 psychological strategies (e.g. imagery) and eight other NPS (e.g. acupuncture). The response rate was 67% (141/214). Subjects were found to be the least familiar with autogenic training, operant conditioning, and cognitive therapy. Other than radiation and surgery, subjects most commonly reported recommending support groups (67%), imagery (54%), music or art therapy (49%) and meditation (43%) for managing cancer pain. Participants were most interested in learning more about acupuncture, massage therapy, therapeutic touch, hypnosis, and biofeedback. Participants were somewhat familiar with most of the 19 NPS presented; however, they use or recommend few NPS for managing cancer pain. Health professionals' interest in NPS has important implications for the supportive care of cancer patients.

Use of preoperative chemotherapy with or without postoperative radiotherapy in technically resectable stage IIIA non-small-cell lung cancer. Provincial Lung Cancer Disease Site Group.

GUIDELINE QUESTION: Should preoperative (neoadjuvant) cisplatin-based chemotherapy with or without postoperative radiotherapy be offered to patients with technically resectable stage IIIA non-small-cell lung cancer (NSCLC) to improve survival? (Resectability should be determined preoperatively by a thoracic surgeon.) OBJECTIVE: To make recommendations about the use of preoperative cisplatin-based chemotherapy with or without postoperative radiotherapy in technically resectable stage IIIA NSCLC. OUTCOMES: Survival is the primary outcome of interest. PERSPECTIVES (VALUES): Evidence was collected and reviewed by 4 members of the Lung Cancer Disease Site Group (LCDSG) of the Cancer Care Ontario Practice Guidelines Initiative. The evidence was then presented to the full LCDSG and discussed extensively at 5 of its meetings. The LCDSG comprises medical and radiation oncologists, pathologists, surgeons, epidemiologists, a psychologist and a medical sociologist. A community representative was present at one meeting during which the recommendation was discussed. QUALITY OF EVIDENCE: Four small randomized controlled trials (RCTs) were available for review; 2 were completed and were reported in full in the literature, 1 was published in abstract form, and 1 was closed and was reported as an interim analysis. Although the RCTs used appropriate clinical trials methodology, including planned interim analyses and early stopping rules, retrospective review revealed inconsistencies between the treatment arms for subsets of stage IIIA disease and for prognostic factors. These factors and the small samples in each study limit the interpretation of the results. BENEFITS: The data from 2 of the 4 trials were not combined because the data were not mature in one case and not extractable in the other. The 2 fully published, completed trials reported a survival benefit for patients treated with preoperative chemotherapy with or without postoperative radiotherapy compared with those not given preoperative chemotherapy. One trial reported a median survival of 26 months in the treatment group versus 8 months in the control group (p < 0.001). A second trial reported an estimated median survival of 64 months versus 11 months (p < 0.008) and a 3-year survival rate of 56% versus 15% respectively. A pooled analysis of the 2-year survival data from the 2 completed RCTs yielded an odds ratio for death of 0.18 (95% confidence interval 0.06 to 0.51) in favour of preoperative chemotherapy. HARMS: There was no difference in the postoperative mortality between the trials reviewed. Toxic effects associated with the chemotherapy were limited primarily to neutropenic fever, nausea and vomiting.