The Rise of Registration Trials
Registration trials are on the rise, with major interest from pharmaceutical companies and actions taken by the National Cancer Institute. It’s a good thing. These trials provide enough evidence of efficacy to support a new drug application filing with the U.S. Food and Drug Administration – speeding new treatments to cancer patients.
Registration trials are more expensive for drug companies to run, and require more effort from our sites. For us, they’re a lot more work to manage. They demand more data and extra levels of scrutiny, leaving the FDA with no doubt about a positive finding. This means more effort by staff at our group chair’s and operations offices and our statistics and data management center. A ton of extra work goes in on budgeting and contracts, protocol development, data collection, query responses, and QA monitoring. The bar is high and the tasks are high-volume.
SWOG Cancer Research Network’s first major dip into prospective registration trial waters was Lung-MAP, the precision medicine trial we launched in 2014. Lung-MAP was designed so that every sub-study would be registration ready – and we’ve opened 11 of them to date!
Every year since, we’ve activated a registration trial – S1404 (melanoma and symptom control and quality of life) in 2015; S1418 (breast) in 2016; and S1605 and S1806 (GU) in 2017 and 2018, respectively.
In addition, there was S0777, a retrospective registration mega project. As I explained in an April blog post , Dr. Brian Durie and his team found that the addition of bortezomib to lenalidomide and dexamethasone significantly lengthened progression-free survival for myeloma patients. These drugs were already approved by FDA, but Celgene Corporation – the makers of lenalidomide – aimed to get the triplet combo approved in Europe. SWOG was approached to retrospectively get S0777 data “registration ready” for submission to the European Medical Association (EMA). This year, the EMA approved the request – after a Herculean effort by our data management and statistical teams that required reconsenting 214 patients, managing over 3,000 case report forms sent in by sites, and handling 9,000 queries. Auditors from our operations office made a stunning 240 monitoring visits, logging over 1,000 visit days.
Registration trials are possible only because of major investments made by the NCI. In recent years, NCI has created or improved trial infrastructure that makes data collection and sharing easier. This includes the centralized, web-based Open Patient Enrollment Network (OPEN) system; Medidata Rave, the cloud–based clinical data management system; the Registration and Credentialing Repository (RCR) for NCI investigators and staff; and Clinical Data Acquisition Standards Harmonization (CDASH), which delivers data traceability and transparency to the FDA.
The bottom line: SWOG and our NCI partners are working harder in order to deliver cancer treatments faster. This acceleration of the drug development process is exactly what government initiatives like Cancer Moonshot, and advocacy groups like Friends of Cancer Research, are all about. They may not be cheap or easy, but registration trials have clear benefits for patients.