{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:34:53Z","timestamp":1762079693173,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T00:00:00Z","timestamp":1670198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rethinking Clinical Trials (REaCT) Program platform at the Ottawa Hospital"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Purpose: To review the successes and challenges of integrating systematic reviews (SRs) into the Rethinking Clinical Trials (REaCT) Program. Methods: All REaCT program SRs were evaluated and descriptive summaries presented. Results: Twenty-two SRs have been performed evaluating standard of care interventions for the management of: breast cancer (n = 15), all tumour sites (n = 4), breast and prostate cancers (n = 2), and prostate cancer (n = 1). The majority of SRs were related to supportive care (n = 14) and survivorship (n = 5) interventions and most (19\/22, 86%) confirmed the existence of uncertainty relating to the clinical question addressed in the SR. Most SRs (15\/22, 68%) provided specific recommendations for future studies and results were incorporated into peer-reviewed grant applications (n = 6) and clinical trial design (n = 12). In 12\/22 of the SRs, the first author was a trainee. All SRs followed PRISMA guidelines. Conclusion: SRs are important for identifying and confirming clinical equipoise and designing trials. SRs provide an excellent opportunity for trainees to participate in research.<\/jats:p>","DOI":"10.3390\/curroncol29120750","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T11:02:10Z","timestamp":1670238130000},"page":"9550-9559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrating Systematic Reviews into Supportive Care Trial Design: The Rethinking Clinical Trials (REaCT) Program"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2462-0581","authenticated-orcid":false,"given":"Bader","family":"Alshamsan","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Medical Oncology, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1H 8L6, Canada"},{"name":"Department of Medicine, College of Medicine, Qassim University, Buraydah 52571, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Hutton","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Program, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Liu","sequence":"additional","affiliation":[{"name":"Cancer Therapeutics Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5921-1441","authenticated-orcid":false,"given":"Lisa","family":"Vandermeer","sequence":"additional","affiliation":[{"name":"Cancer Therapeutics Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-8219","authenticated-orcid":false,"given":"Mark","family":"Clemons","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Medical Oncology, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1H 8L6, Canada"},{"name":"Cancer Therapeutics Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1016","DOI":"10.1200\/JOP.2016.013474","article-title":"Novel methodology for comparing standard-of-care interventions in patients with cancer","volume":"12","author":"Hilton","year":"2016","journal-title":"J. Oncol. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1200\/JCO.2009.27.5404","article-title":"Equipoise lost: Ethics, costs, and the regulation of cancer clinical research","volume":"28","author":"Stewart","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e276","DOI":"10.3747\/co.23.2394","article-title":"Can the referring surgeon enhance accrual of breast cancer patients to medical and radiation oncology trials? The ENHANCE study","volume":"23","author":"Arnaout","year":"2016","journal-title":"Curr. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5381","DOI":"10.1158\/1078-0432.CCR-10-1273","article-title":"Phase III clinical trial development: A process of chutes and ladders","volume":"16","author":"Dilts","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1056\/NEJM198707163170304","article-title":"Equipoise and the ethics of clinical research","volume":"317","author":"Freedman","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1136\/bmj.321.7263.756","article-title":"For and against: Clinical equipoise and not the uncertainty principle is the moral underpinning of the randomised controlled trial","volume":"321","author":"Weijer","year":"2000","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3959","DOI":"10.3390\/curroncol28050337","article-title":"The rethinking clinical trials (REaCT) program. A Canadian-led pragmatic trials program: Strategies for integrating knowledge users into trial design","volume":"28","author":"Saunders","year":"2021","journal-title":"Curr. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10549-019-05274-0","article-title":"Creating a pragmatic trials program for breast cancer patients: Rethinking Clinical Trials (REaCT)","volume":"177","author":"Basulaiman","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_9","unstructured":"Petticrew, M., and Roberts, H. (2008). Systematic Reviews in the Social Sciences: A Practical Guide, John Wiley & Sons."},{"key":"ref_10","unstructured":"(2021, December 14). Cochrane Handbook for Systematic Reviews of Interventions, Cochrane Training. Available online: https:\/\/training.cochrane.org\/handbook."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1002\/sim.1875","article-title":"Combination of direct and indirect evidence in mixed treatment comparisons","volume":"23","author":"Lu","year":"2004","journal-title":"Stat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1136\/bmj.331.7521.897","article-title":"Simultaneous comparison of multiple treatments: Combining direct and indirect evidence","volume":"331","author":"Caldwell","year":"2005","journal-title":"BMJ"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, T., Puhan, M.A., Vedula, S.S., Singh, S., Dickersin, K., and Ad Hoc Network Meta-analysis Methods Meeting Working Group (2011). Network meta-analysis-highly attractive but more methodological research is needed. BMC Med., 9.","DOI":"10.1186\/1741-7015-9-79"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"777","DOI":"10.7326\/M14-2385","article-title":"The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: Checklist and explanations","volume":"162","author":"Hutton","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"l6890","DOI":"10.1136\/bmj.l6890","article-title":"Synthesis without meta-analysis (SWiM) in systematic reviews: Reporting guideline","volume":"368","author":"Campbell","year":"2020","journal-title":"BMJ"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jbo.2013.05.001","article-title":"A systematic review of dosing frequency with bone-targeted agents for patients with bone metastases from breast cancer","volume":"2","author":"Hutton","year":"2013","journal-title":"J. Bone Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.ctrv.2015.09.007","article-title":"Identifying an optimal antiemetic regimen for patients receiving anthracycline and cyclophosphamide-based chemotherapy for breast cancer\u2014An inspection of the evidence base informing clinical decision-making","volume":"41","author":"Hutton","year":"2015","journal-title":"Cancer Treat. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1093\/annonc\/mdv284","article-title":"Should de-escalation of bone-targeting agents be standard of care for patients with bone metastases from breast cancer? A systematic review and meta-analysis","volume":"26","author":"Ibrahim","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1634\/theoncologist.2014-0381","article-title":"Is there a role for oral or intravenous ascorbate (vitamin C) in treating patients with cancer? A systematic review","volume":"20","author":"Jacobs","year":"2015","journal-title":"Oncologist"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10549-015-3434-z","article-title":"Management of urogenital atrophy in breast cancer patients: A systematic review of available evidence from randomized trials","volume":"152","author":"Mazzarello","year":"2015","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.clbc.2016.07.014","article-title":"Optimal management of leptomeningeal carcinomatosis in breast cancer patients\u2014A systematic review","volume":"16","author":"Dudani","year":"2016","journal-title":"Clin. Breast Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1007\/s00520-015-2941-0","article-title":"Treatment of taxane acute pain syndrome (TAPS) in cancer patients receiving taxane-based chemotherapy\u2014A systematic review","volume":"24","author":"Fernandes","year":"2016","journal-title":"Support. Care Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1007\/s00520-016-3256-5","article-title":"Taxane acute pain syndrome (TAPS) in patients receiving taxane-based chemotherapy for breast cancer\u2014A systematic review","volume":"24","author":"Fernandes","year":"2016","journal-title":"Support. Care Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e117","DOI":"10.1016\/j.clcc.2016.02.011","article-title":"Management of epidermal growth factor receptor inhibitor-induced hypomagnesemia: A systematic review","volume":"15","author":"Jiang","year":"2016","journal-title":"Clin. Colorectal Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clgc.2016.07.018","article-title":"A systematic review of the incidence and risk factors for taxane acute pain syndrome in patients receiving taxane-based chemotherapy for prostate cancer","volume":"15","author":"Fernandes","year":"2017","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10549-016-4028-0","article-title":"Optimal primary febrile neutropenia prophylaxis for patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer: A systematic review","volume":"161","author":"Fernandes","year":"2017","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_27","first-page":"1","article-title":"Primary febrile neutropenia prophylaxis for patients who receive FEC-D chemotherapy for breast cancer: A systematic review","volume":"4","author":"Fernandes","year":"2018","journal-title":"J. Glob. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ctrv.2018.06.015","article-title":"Optimal sequence of adjuvant endocrine and radiation therapy in early-stage breast cancer\u2014A systematic review","volume":"69","author":"McGee","year":"2018","journal-title":"Cancer Treat. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s10549-018-4868-x","article-title":"Optimal vascular access strategies for patients receiving chemotherapy for early-stage breast cancer: A systematic review","volume":"171","author":"Robinson","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s10549-019-05265-1","article-title":"De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: A systematic review and meta-analysis","volume":"176","author":"Awan","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/s13643-019-1243-x","article-title":"Benefits and harms of medical cannabis: A scoping review of systematic reviews","volume":"8","author":"Pratt","year":"2019","journal-title":"Syst. Rev."},{"key":"ref_32","first-page":"E86","article-title":"Comparing interventions for management of hot flashes in patients with breast and prostate cancer: A systematic review with meta-analyses","volume":"47","author":"Hutton","year":"2020","journal-title":"Oncol. Nurs. Forum"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e362","DOI":"10.1016\/j.clbc.2021.10.003","article-title":"Time to update evidence-based guideline recommendations about concurrent tamoxifen and antidepressant use? A systematic review","volume":"22","author":"Bradbury","year":"2022","journal-title":"Clin. Breast Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s00520-020-05556-0","article-title":"Long-term impact of bone-modifying agents for the treatment of bone metastases: A systematic review","volume":"29","author":"Ng","year":"2021","journal-title":"Support. Care Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"LeVasseur, N., Cheng, W., Mazzarello, S., Clemons, M., Vandermeer, L., Jones, L., Joy, A.A., Barbeau, P., Wolfe, D., and Ahmadzai, N. (2021). Optimising weight-loss interventions in cancer patients\u2014A systematic review and network meta-analysis. PLoS ONE., 16.","DOI":"10.1371\/journal.pone.0245794"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102254","DOI":"10.1016\/j.ctrv.2021.102254","article-title":"De-escalating adjuvant therapies in older patients with lower risk estrogen receptor-positive breast cancer treated with breast-conserving surgery: A systematic review and meta-analysis","volume":"99","author":"Savard","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102188","DOI":"10.1016\/j.ctrv.2021.102188","article-title":"The COVID-19 pandemic: An opportunity to rethink and harmonise the frequency of follow-up visits for patients with early stage breast cancer","volume":"97","author":"Surujballi","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_38","unstructured":"Bourque, J.M., and McGee, S. (2021, November 12). Evaluating Optimal Timing of Endocrine Therapy and Radiation Therapy in Early-Stage Breast Cancer (REaCT-RETT), NCT03948568, ClinicalTrials.gov, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03948568."},{"key":"ref_39","unstructured":"Savard, M.F. (2021, November 12). Evaluating Harms and Benefits of Endocrine Therapy in Patients \u226570 Years of Age with Lower Risk Breast Cancer, NCT04921137, ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04921137."},{"key":"ref_40","unstructured":"Clemons, M. (2021, December 15). Individualised Versus Standard Care for Breast Cancer Patients at High-Risk for Chemotherapy-Induced Nausea and Vomiting the ILIAD Study, NCT02861859, ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02861859."},{"key":"ref_41","unstructured":"Clemons, M. (2021, November 12). Granulocyte-Colony Stimulating Factors or Antibiotics for Primary Prophylaxis for Febrile Neutropenia, NCT02816112, ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02816112."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.annonc.2020.04.005","article-title":"A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer","volume":"31","author":"Clemons","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s10549-019-05388-5","article-title":"A multicentre, randomized pilot trial comparing vascular access strategies for early stage breast cancer patients receiving non-trastuzumab containing chemotherapy","volume":"178","author":"Robinson","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100388","DOI":"10.1016\/j.jbo.2021.100388","article-title":"Two-year results of a randomised trial comparing 4- versus 12-weekly bone-targeted agent use in patients with bone metastases from breast or castration-resistant prostate cancer","volume":"30","author":"Clemons","year":"2021","journal-title":"J. Bone Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ejca.2020.08.019","article-title":"A randomised trial of 4- versus 12-weekly administration of bone-targeted agents in patients with bone metastases from breast or castration-resistant prostate cancer","volume":"142","author":"Clemons","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_46","unstructured":"Clemons, M. (2021, November 12). Comparing a Single-Dose vs. Twice Yearly Zoledronate in Patients with Early Stage Breast Cancer (REaCT-ZOL), NCT03664687, ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03664687."},{"key":"ref_47","unstructured":"Ng, T. (2021, November 12). Comparing Continuation or De-Escalation of Bone Modifying Agents (BMA) in Patients Treated for Over 2 Years for Bone Metastases from Either Breast or Castration-resistant Prostate Cancer, NCT04549207, ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04549207."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5787","DOI":"10.1007\/s00520-021-06142-8","article-title":"A prospective multi-centre, randomized study comparing the addition of tapering dexamethasone to other standard of care therapies for taxane-associated pain syndrome (TAPS) in breast cancer patients","volume":"29","author":"Clemons","year":"2021","journal-title":"Support. Care Cancer"},{"key":"ref_49","unstructured":"Vickers, M. (2021, November 12). Feasibility of Using an Integrated Consent Model to Compare Two Standard of Care Regimens for the Management of Hypomagnesemia from Anti-Cancer Therapies, NCT02690012, ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02690012."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.breast.2020.11.002","article-title":"A randomized trial of individualized versus standard of care antiemetic therapy for breast cancer patients at high risk for chemotherapy-induced nausea and vomiting","volume":"54","author":"Clemons","year":"2020","journal-title":"Breast"},{"key":"ref_51","unstructured":"(2021, August 01). REaCT: REthinking Clinical Trials. Available online: https:\/\/react.ohri.ca\/."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/29\/12\/750\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:34:15Z","timestamp":1760146455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/29\/12\/750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,5]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["curroncol29120750"],"URL":"https:\/\/doi.org\/10.3390\/curroncol29120750","relation":{},"ISSN":["1718-7729"],"issn-type":[{"type":"electronic","value":"1718-7729"}],"subject":[],"published":{"date-parts":[[2022,12,5]]}}}