OCOG is versatile and over the years has conducted phase I first-in-human trials, phase II and large phase III randomized clinical trials. Over the last decade a major theme of OCOG trials has been the evaluation of new technologies and their adoption into clinical practice.

New and expensive imaging technologies are often introduced into clinical practice before there is evidence that they are better than existing modalities. One such example is Positron Emission Tomography (PET), which is an imaging technique that is attractive in oncology because of the preferential uptake of radiolabelled glucose by cancer cells compared to non-cancer cells. OCOG has conducted a program of eight clinical trials supported by Cancer Care Ontario and the Ontario Ministry of Health & Long-Term Care (MOHLTC). The trials include: operable early stage non-small cell lung cancer (NSCLC) (PIs: G Darling, D Maziak); locally advanced NSCLC (PI: Y Ung); early stage breast cancer (PI: K Pritchard); head and neck cancer (PI: J Waldron); colorectal cancer metastatic to liver (PIs: CA Moulton, S Gallinger); recurrent solid tumors (PI: J You); locally advanced cancer of the cervix (PIs: L Elit , A Fyles); muscle invasive bladder cancer (PIs: S Shridhar, N Power, S Mukherjee, U Metser); and locally advanced breast cancer (PIs: I Dayes, A Eisen, R George, U Metser). When the trials began, there was little experience with PET in Ontario. As a result, OCOG established quality assurance programs for the performance of the PET scans and for reading of the scans across the sites. By introducing this technology in a standardized and organized manner, broader healthcare has been improved. Over 2000 patients have been enrolled in these trials and OCOG's PET evaluation program is the largest of its kind in the world. The results of these studies have informed health policy in Ontario and have had significant impact on cancer patients worldwide.

OCOG is recognized internationally for its trials of novel radiation therapy regimens after breast cancer surgery and in radiation therapy in men with early stage prostate cancer. An example of a particularly impactful trial is the OCOG RAPID trial (PIs: T Whelan and I Olivotto), which compared accelerated partial breast irradiation (APBI) twice a day for 5 days with standard whole breast irradiation (WBI) over 3 weeks following lumpectomy in women with early stage breast cancer. The goal of shortening radiation treatment is important because of its impact on patient convenience. The APBI regimen uses high doses of radiation delivered to a targeted area while sparing the surrounding normal tissues. The results of the trial showed that the shorter treatment was non-inferior to WBI, but that it was associated with a worse cosmetic result due to increased scarring and thickening of the breast tissue. This is a very important result as in the United States there has been an unconstrained adoption of short high-dose radiation regimens in regular practice. These results have discouraged the use of such radiation regimens outside of the research setting.

OCOG completed the PROFIT trial (PIs: H Lukka, CN Catton) in men with intermediate risk localized prostate cancer. They were randomized to standard usual radiation with 78 Gy in 39 fractions over 8 weeks or hypo-fractionated radiation with 60 Gy in 20 fractions over 5 weeks. The hypo-fractionated regimen was non-inferior to standard RT in terms of efficacy and there was no increase in late toxicity. As a result of the PROFIT trial patients with prostate cancer are receiving shorter radiation treatments.

For many years, methodologists at OCOG have had links to the thrombosis research program at McMaster University. The OCOG Division of Thrombosis, established by the late Dr. Clive Kearon, has focused on improving the diagnosis and treatment of venous thromboembolism. The Division of Thrombosis were responsible for study design and served as the Data Coordinating Centre of the NIH-funded trial, Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis (ATTRACT), published in the New England Journal of Medicine (PIs: C. Kearon, J. Julian, S. Parpia), that showed that catheter-based thrombus removal had very limited ability to prevent the "post-thrombotic syndrome" after DVT. The group is now conducting a NIH-funded trial, Chronic Venous Thrombosis: Relief with Adjunctive Catheter Directed Therapy (C-TRACT), evaluating catheter-based treatments for established post-thrombotic syndrome.

OCOG was established in 1982 by the Ontario Cancer Treatment & Research Foundation (OCTRF) with funding initially provided by the Ontario Lottery Corporation to recognize the importance of clinical research in improving health care and as a way to develop, coordinate and promote cancer clinical trials throughout Ontario's regional cancer centres and the Princess Margaret Hospital. The OCOG Coordinating & Methods Centre (CMC) was established in the former Department of Clinical Epidemiology & Biostatistics (CE&B) at McMaster University. Dr. Peter McCulloch was the initial OCOG director and Dr. Mark Levine, a medical oncologist and methodologist from the Hamilton Regional Cancer Centre, helped found OCOG and soon became its director.

In 1988, the Clinical Trials Methodology Group (CTMG) was established as a program within the Henderson Research Centre and OCOG became part of CTMG. CTMG also conducted trials in venous thrombosis and cardiovascular disease. In 2002, Dr. Mark Levine assumed the role of Director of CTMG and the focus of CTMG became oncology trials. In December 2007, OCOG joined McMaster University's new Department of Oncology. In 2011, the Escarpment Cancer Research Institute (ECRI) was established as a joint venture between the Hamilton Health Sciences and McMaster University. OCOG is one of the core components of ECRI.

The trials conducted at OCOG are supported from several sources including peer-review grants from the Canadian Institutes of Health Research, the Canadian Cancer Society, the Canadian Breast Cancer Research Alliance, Cancer Care Ontario, the Ontario Institute for Cancer Research, the National Institutes of Health, the Heart & Stroke Foundation, the Ontario Ministry of Health and Long-Term Care, and from the pharmaceutical industry.