Blame Avandia. It was that diabetes blockbuster’s black box warning late in 2007 that got Jonathan Goldman thinking.
Chief medical officer of Icon Medical Imaging, Goldman pondered whether the FDA would start requiring diabetes drug developers to do more to monitor cardiovascular events. Then, last summer, the FDA’s endocrinologic and metabolic drugs advisory committee met. That galvanized Goldman into action.
“I strongly suspected the FDA was going to require more trials,” says Goldman, a cardiologist. “Here you have a huge new class of drugs. One already has a black box warning. I figured, it can’t be long before FDA mandates more unbiased data.”
Goldman asked his team at Icon to work on applications that would keep track of cardiovascular events specifically in diabetes trials. In real time. The goal: to accelerate the adjudication of such events.
Sure enough, last December, the FDA released such guidance, requiring more long-term testing for cardiovascular events of patients in diabetes trials. The agency also mandated more phase IV trials to look at cardiac safety for diabetes drugs already on the market. And FDA is insisting on more robust design and data collection approaches in phase II and III.
By that point, a new component of the firm’s in-house clinical trial management system was already available. The company had built a diabetes-focused module for its Medical Imaging Review and Analysis (MIRA) system. Goldman says MIRA allows online access for clinical data management, image analysis, project management and document management, and has integrated electronic case report forms (eCRFs).
Icon Clinical Research (NASDAQ: ICLR) is a Dublin-based contract research organization (CRO) that is the parent of Goldman’s Philadelphia-based imaging group. The firm focuses on the cardiology space, and has worked with 35,000 patients in cardiovascular endpoint trials over the last five years.
The Icon imaging group has supplemented its clinical experience in adjudication with a cardiovascular-centric advisory board that provided advice on the design of the new electronic adjudication module in MIRA.
Objective vs. Subjective
Thus far, the module has been used in four cardiovascular outcome trials. The system digitally stores all data relevant to the adjudication of cardiovascular events—including CRF output, patient charts, laboratory results, ECG, echocardiogram, coronary angiogram, peripheral angiogram and X-rays—in a digital format. Adjudicators in different locations can simultaneously access and review all such data securely, completing the assessment in an electronic CRF.
Goldman notes that the FDA is now requiring independent adjudication of cardiovascular outcomes. It’s no longer enough just to have the thinking of one investigator at the clinical site. Independent adjudication allows sponsors conducting event-driven trials to be rigorously consistent in their diagnoses, using a system of checks and balances.
In clinical practice, Goldman explains, diagnosis of myocardial infarction can be inconsistent. One doctor might decide a patient has had such an event if, say, a blood test detected a marker for heart muscle damage. But the gold standard for diagnosis involves at least two of three factors: the aforementioned blood work; complaints of chest pain; and confirmation of damage on ECG. With the MIRA system, principal investigators would be required to include all three, so that diagnosis is very clear. So the firm’s technology prevents subjective interpretations.
The MIRA system also increases consistency of diagnosis by using logic-driven eCRF, says Goldman. This ensures that, for instance, if the answer is “yes” to the question, Did the patient die? the adjudicator cannot complete sections about subsequent outcomes.
To the best of his knowledge, Goldman says, competitors such as Perceptive Informatics have not developed comparable systems. One rival, ERT, has recently partnered with Icon for the inclusion and analysis of ECG in the cardiac safety components of clinical trials, according to Goldman.
The real-time aspect is crucial, Goldman says. Sponsors are aiming for large numbers of patients to get an accurate quantification of the prevalence of side effects. For instance, the percentage of patients expected to have a heart attack might be between 2 and 4 percent. So perhaps 10,000 patients would be needed to get 200 to 400 patients at increased risk for myocardial infarction. And then, under the new FDA guidance, those cases must be watched closely. In previous cardiac-focused trials, using paper or a cumbersome system, Goldman says, it wasn’t possible to monitor such patients in real time.
“The pen and paper way, every three or six months, all involved with the trial would sit around a table and say let’s vote on this or that,” says Goldman. “It was more variable, more ad hoc, with a very poor audit trail. And you might be enrolling for months and not know how many [events] you have.”
MIRA’s new module, he says, has a built-in tracking system. It will monitor what data has been collected—and what’s missing. “You can keep an electronic tally in real time,” says Goldman. “That becomes very, very important if you do a big diabetes study—say, 10 countries with 500 sites with up to five years of follow up. That’s a huge amount of data to be acquired and adjudicated. This leads to an additional important benefit for sponsors. With these large trials costing approximately $100 million, the cost savings of the MIRA system can amount to $500,000 per week for allowing earlier completion of the trial.”
Put another way, Goldman says using MIRA for a diabetes-drug trial that must scrutinize cardiac safety will run about 1 percent of the overall cost of the trial.
—by Suz Redfearn
Editor’s note: Here’s an earlier article on the company’s imaging system.d9A2t49mkex