A boom in cancer drug development has flooded the nation's largest research institutions with clinical trial requests, which some say are making the system bloated and inefficient.
"Most institutions have many more trials open than need to be open," said John DiPersio, deputy director of the Alvin J. Siteman Cancer Center in St. Louis, home to more than 500 open clinical trials by DiPersio's estimates.
Immuno-oncology, a branch of research that looks at how the immune system can be used to fight cancer, is largely the culprit. The field took off in the last five years with the success of Merck & Co.'s Keytruda and Bristol-Myers Squibb's Opdivo, and it remains a top investment area for pharma.
Informa, an industry data provider, counted 2,731 immuno-oncology R&D projects in the works this year, up 16% from 2018. Keytruda alone is under investigation across more than 1,000 trials.
Many of the projects rely on studies conducted at large, urban institutions like MD Anderson Cancer Center in Houston, Memorial Sloan Kettering in New York or Moffitt Cancer Center in Tampa, Florida. These sites have experience running clinical trials and the infrastructure, such as nursing support and imaging tools, required to meet patient and data collection needs.
They also see more patients than rural or community-based centers, which can help to speed up enrollment. That's especially true when the study is for a rare cancer — Ferran Prat, head of industry relations at MD Anderson, estimates about half of all U.S. cases of osteosarcoma come through the center.
The industry's oncology investments are a business boon for these institutions, but they're also posing challenges. Prat notes how the higher volume of clinical trial requests is causing MD Anderson to be more selective about which studies it takes on and which companies it works with.
"Many of them are still under the old paradigm that if they ask us to conduct a trial, we will of course do it," Prat told BioPharma Dive. "The reality is we're saying no more and more often, because we don't think the science is meritorious."
Doctors have also run into difficulties filling all the newly available trials.
DiPersio estimates about a quarter to a third of cancer clinical investigations are open for a year without anyone enrolling in them. He said empty trials are not only an "economic drain" on institutions because of the regulatory and logistical work that goes into opening a site, but they're also reflective of broader enrollment issues.
Industry and academia claim that just 5% of cancer patients ever participate in clinical trials, but many believe the percentage could increase if enrollment criteria weren't so restrictive. Mild abnormalities in lab tests or a hepatitis infection from decades ago are some of reasons patients have been denied entry into trials.
"It's very disappointing after all this effort, all these tests, all this time, and the multiple visits to find out that they missed the criteria by a little bit," DiPersio said.
Merck and Pfizer are among the drug giants that say they want to make trials more accessible and efficient.
Eric Rubin, vice president of global clinical oncology at Merck Research Laboratories, said one priority has been offering more community sites once a drug is in the larger, later phases of development.
"If they can sign up at their local site rather than have to drive into New York City or something, that may make the difference for them participating in the trial versus not participating," Rubin told BioPharma Dive.
Pfizer has more than 125 ongoing cancer clinical trials operating out of nearly 3,200 sites globally. Chris Boshoff, chief development office at Pfizer Oncology, said enrolling patients outside of large research institutions hasn't been a substantial problem, but notes there's "a lot of space for improvement" with cancer clinical trials in general.
DiPersio contends that one sticking point is the lack of dialogue between sites and sponsors after the study protocol has been approved. A meeting before the site initiation may lead to a simpler protocol that's easier on patients, he said.
"Can the burden on the patient be reduced? Nobody asks that question. Like, why are you doing a bone marrow test every three months? Or do we really need to biopsy this tumor three different times?"
Another lingering question is whether certain immuno-oncology agents warrant so much clinical focus.
For example, the Food and Drug Administration has already approved six medicines that target an immune system pathway called PD-1, including Keytruda and Opdivo, and more are on the way.
A large number of clinical trials are testing these drugs in different tumor types or in combination with other therapeutics. While readouts have been compelling in areas such as kidney cancer, there are concerns that other potential therapies may not get enough attention.
"You have all these companies trying to support their share price because they have to have an immunotherapy drug out there in the market," Joseph Unger, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, told BioPharma Dive.
As a result, they're "collectively slowing down the development of this class of drugs by having too many drugs that are really the same thing in too many clinical trials."
The crowding isn't universal, however.
Pfizer's Boshoff said he often hears that U.S. academic sites have many immunotherapy studies for first-line lung cancer, but that's "a very unique situation right now."
"Globally, it's much less of an issue," he said.
Still, the greater amount of trials and competition puts pressure on doctors to deliver meaningful results. In fact, one of the criteria drugmakers consider when selecting a site is whether it has a history of producing quality data quickly.
"There's an enormous amount of pressure and cost to the institutions to hire lots of clinical trial assistants, to not only make sure the patients on study are getting the right treatments, but also that the data are being entered into the database in a timely fashion," DiPersio said.
Money isn't as much of an issue at MD Anderson, according to Prat. As a state agency, it can only offer its services at fair market value.
Rather, the limiting factor is time and resources.
"We have to gear up to be able to have more bandwidth," he said, "and it's something we're trying to improve every day."