BioPharma Dive sat down with our Gary Fishbein for a conversation on how to de-risk trials without sacrificing cost or speed.
Phase 3 oncology studies have approximately a 35% likelihood of leading to regulatory approval. There are particular challenges for oncology studies, in view of the fact that the overall likelihood of non-oncology Phase 3 studies leading to approval averages 65%. Oncology medical monitors play a critical role in the clinical development and execution of pivotal oncology trials, and often have strongly influenced the therapeutic area in which the compound will be most active, along with identifying and managing drug-related toxicity. These measures, applied across the continuum of a compound’s development, can improve the likelihood of successful late phase trials.
In recent years, strategic and data-centric tools have provided physicians and other medical experts the ability to assess safety and efficacy signals earlier in the course of the clinical trial. Doing so can set programs up for success by optimizing enrollment, assessing safety signals and working with sites — all while informing protocol changes in real time.
“Every sponsor company of every size should pay attention to how they perform medical monitoring,” said Gary Fishbein, MD, MPH, Vice President, Therapeutic Area Lead for Oncology at Worldwide Clinical Trials. “This process contributes to data integrity throughout the trial, from making sure the right patients are participating to ensuring you’re collecting the right data that addresses the protocol’s original scientific question and fits within the framework of oncology drug development.”
And yet, in this moment of intense competition and pressure to do more faster, medical monitoring programs should not only be comprehensive — they should also be efficient. We sat down with Dr. Fishbein to learn how to strike the right balance and de-risk trials without sacrificing cost or speed.
While medical monitors are perhaps best known for surveilling adverse events and other safety concerns after the trial begins, they can be just as influential at the outset by evaluating inclusion and exclusion criteria. After all, trials have historically received criticism for not having the right people involved — and if you can optimize enrollment parameters at the get-go, it makes for more efficient onboarding for all.
“We’re looking at many variables when defining who should or shouldn’t participate in a trial,” Dr. Fishbein said. “Aspects like bone marrow function, liver enzymes, kidney function, and other factors can influence outcomes quite a bit — and medical monitors’ knowledge about these patient populations are highly valuable in this context.”
For example, he said, if you’re studying a liver cancer drug, you most certainly want to evaluate other drugs participants might be taking that are metabolized through the liver and could interact with the investigated therapeutic. Those individuals might be excluded from a safety perspective.
But there might also be occasions when an experienced medical monitor can widen the aperture of study inclusion so that more patients can be a part of it, he added.
“As medical monitors, we see where patients screen fail, and we can assess whether there is flexibility in adjusting these clinical or laboratory features,” he said. “If you can scrutinize the protocol and ask whether there’s room to amend things without compromising patient safety, you can create opportunities to make studies more accessible to more people.”
Assessing safety signals
Even with optimized enrollment, adverse events occur. You can onboard all the right people under a medical monitor’s guidance but still have unexpected safety events develop downstream. When that happens, medical monitors offer continuing expertise to adapt protocol design in real time.
“It may not be clear which patients may manifest certain side effects that would limit the ability to escalate the dose of an oncology drug,” Dr. Fishbein said. “But there are several tactics medical monitors can employ, such as issuing an amendment to split the patients into two dose categories based on concomitant medications that they require. An example of this is seen in leukemia studies, where antifungal agents, which are required to prevent reactivation of infection, may compete for important pathways of metabolism with the drug that is under study. Study arms can be set up to evaluate the study drug in patients who are on highly competing antifungal agents and for those who are on less inhibitory antifungals.”
Sometimes, the midstream change might not even require a different dose.
“You might just institute more frequent specialist exams,” Dr. Fishbein said, adding that the importance of that surveillance step is twofold: “It’s not just that the side effect creates a safety issue which can jeopardize a person’s quality of life, but we also need to control those side effects in order to observe the optimal efficacy impact of the drug. The medical monitor needs to institute measures so that the anticancer potential of a compound can be fully and fairly evaluated.”
In these cases, advanced technologies such as data visualization can help, he added. Such platforms create easy-to-access charts and graphs that help medical monitors as well as sponsors identify and even predict patterns of anticipated toxicity.
Working with sites for a more efficient approach
Ultimately, these best practices all depend on the sponsor and CRO study staff having a good relationship with sites. From holding a comprehensive site initiation visit to maintaining close communication long term, Dr. Fishbein said, it’s critical for medical monitors to establish and keep up the partnership so that accurate decisions can be made about whether a particular drug is active.
“From the time of study start-up, we’re developing detailed slide decks for the sites that will describe the protocol, disease indications, toxicity concerns, mitigations to manage side effects, and how we’ll work together throughout the trial,” he said. “At the end of that discussion, we’ve often exchanged phone numbers and emails so that we can support our study sites throughout patient enrollment and treatment. It’s very collaborative and highly motivating for both the research sites and the drug developers.”
After all, he said, these are oncologists who also hope to see the therapy succeed. And with a robust effort that contributes to better, cleaner data — in a more efficient way — medical monitors are a critical piece to making that happen.
Learn how medical monitoring from Worldwide Clinical Trials can help de-risk your oncology clinical trials protocol for faster and more efficient study startup.
Previously published on BioPharma Dive on July 11th, 2022