Empowering Clinicians and Researchers with Real-World Evidence

Mayo Clinic Platform has developed tools that enable users to find new diagnostic and treatment solutions.

By John Halamka, M.D., Diercks President, Mayo Clinic Platform and Paul Cerrato, MA, senior research analyst and communications specialist, Mayo Clinic Platform

Clinicians and investigators often encounter limitations in the knowledge resources they use. The latest published clinical trials, as well as the most recent professional guidelines, often fall short of giving users the entire picture. Widely available tools do not include the vast treasure trove of information available in electronic medical records: real-world evidence. These records may contain imaging data, clinical notes, medical claims data, lab reports, vital signs, and much more. With this in mind, Mayo Clinic Platform has spent the last several years building data discovery capabilities which could be described as a “search engine for real-world patients".

Gelareh Zadeh, MD, PhD, chair of the Department of Neurological Surgery for Mayo Clinic, has leveraged this capability to help answer questions like: What factors influence outcome for brain tumors such as blood sugar, hemoglobin, white blood count, and many multiple other clinical parameters? What fraction of meningioma patients received radiation? How long is the wait time from diagnosis to surgery the safe limit of care? To answer the question about radiation therapy, she initially collected her own cohort of 2,154 patients, which took five years to build. On the other hand, it took her only a few minutes when she utilized Mayo Clinic Platform's discovery capabilities to access its range of de-identified clinical data and created a cohort of 6,545 patients.

Mayo Clinic Platform's de-identified data environment enables users to define inclusion/exclusion, demographics, drug exposures, labs, and imaging, compare cohorts, test hypotheses, and rapidly (within minutes) compare outcomes. For example, Dr. Zadeh wanted to see what kind of relationship exists between glucose and glioblastoma (GBM), one of the most lethal brain cancers. The cancer is resistant to surgery, radiation, and chemotherapy, with a median survival of 16 months. Research from her laboratory shows that GBM, as many other cancers, feed on sugar and how they process glucose results in more aggressive tumor growth. Based on these findings, she postulated that patients with GBM may suffer adverse effects from hyperglycemia. Patients with GBM are usually given a drug to help with brain swelling, called dexamethasone. Dexamethasone increases blood sugar. Taking all this information into consideration she hypothesized and explored her hypothesis on Mayo Clinic Platform to investigate the relationship between glucose levels and clinical outcomes in patients with GBM. There are over 7,000 GBM patient records currently available on the platform, which is a remarkable dataset. Her analysis revealed that after a diagnosis of GBM, survival is worse among patients with elevated hemoglobin A1c, compared to patients who have normal HbA1c. A similar relationship was found between elevated fasting glucose and GBM survival. Using this data, Dr. Zadeh also found a significant relationship between high fasting glucose and lung, breast, and colorectal cancers.

These findings are consistent and in support of one of the key areas of research focus in the Dr. Zadeh’s laboratory, which is to investigate  the phenomenon in cancer called the Warburg effect. OpenEvidence explains: “The Warburg effect refers to the phenomenon in which cancer cells preferentially metabolize glucose to lactate via glycolysis even in the presence of sufficient oxygen, rather than relying primarily on mitochondrial oxidative phosphorylation for energy production. This process is termed "aerobic glycolysis" and distinguishes tumor metabolism from that of most normal differentiated cells, which utilize oxidative phosphorylation under normoxic conditions.” In plain English, it implies that sugar feeds cancer. That naturally begs the question: Does dietary sugar increase the risk of cancer or speed up its development?

According to the American Cancer Society, dietary sugar does not directly feed cancer cells; ACS nonetheless recommends limiting “highly processed foods containing high levels of added sugars, such as cakes, candy, cookies, and sweetened cereals, as well as sugar-sweetened beverages, such as soda, sports drinks, and energy drinks. [This] can help to reduce caloric intake, minimize weight gain, and promote a healthier body weight as well as lower insulin secretion in individuals with metabolic abnormalities, such as those with prediabetes or type 2 diabetes.” In addition, large prospective cohort data also indicate that higher total and added sugar intake is associated with increased overall and breast cancer risk, even after adjusting for weight gain.

Based on these findings, Dr. Zadeh and her team — including Dr. Asad Lone, a postdoctoral fellow, and Dr. Leo Yefet, a neurosurgery resident and PhD student — collaborated closely with colleagues in endocrinology, Dr. Jian Shah, and neuro-oncology, Dr. Pankaj Campian, to launch a phase 2 randomized clinical trial. The study compares continuous glucose monitoring (CGM) with blood sugar regulation to CGM with the current standard of care. Through the Rapid Activation Trials (RAT) and help of the Mayo Clinic trials and IRB team, this clinical trial was activated in seven weeks and actively recruiting patients.

A next generation of tools that leverage secure data environnments from sources around the world will enable clinical trials to be validated, repeated, and refined at a pace which will far exceed our historical experience. Dr. Zadeh and her team showed us how discovery can be done in days not years.