Too Many Amendments, Too Little Planning, Expert Says

March 25, 2019

The rise in the number of protocol amendments occurring before the first patient has even received the first dose is a reflection of failure in planning trial design, says Ken Getz, director of sponsored research programs at the Tufts Center for the Study of Drug Development.

Amending a protocol often means adding endpoints, distinct procedures and patient visits that may not be strictly necessary, Getz said in a webinar last week. “You don’t have to gather data or report on every finding,” he said.

Sometimes added complexity comes from risk avoidance: Companies want to hedge against even a slight chance that a regulatory agency will ask a question. It is also borne from the trend of gathering subjective outcomes and comparative effectiveness data or incorporating additional data from sources such as wearables and smartphone apps.

“No one is questioning the strategic value of many of these supporting tertiary and exploratory endpoints,” Getz said. “The real issue, however, is that when we add another endpoint, there are procedures supporting it. And as we start to aggregate all those procedures it has a huge impact on performance downstream.”

For example, adding additional data points means greater demand for resources to coordinate them. Exploratory endpoints might mean more visits or more procedures per visit, which takes more time and effort not only for those who administer them, but also for trial volunteers.

More complex protocols have numerous costs, ranging from hard dollars to time to participant satisfaction. “The more complex our protocols, the worse we perform — as measured by our recruitment and retention rate [and] our cycle times — for virtually every task that we have measured,” Getz said.

The solution? Better planning in the trial design stage. Companies increasingly are turning to such solutions as:

  • Protocol authoring tools that help create “a greater line of sight” between every procedure performed and the endpoint that it supports;
  • Feasibility review committees that can challenge procedures not associated with essential endpoints; and
  • Patient advisory boards that review draft protocols and look for ways to make participation less burdensome — one of the major factors volunteers cite in their decision not to participate.

Getz also points out that technology can help. “A number of companies are relying increasingly on the use of data, particularly electronic health and medical data, to help guide protocol design practices and determine whether eligibility criteria will make it more difficult to find study volunteers,” Getz said.

“Complexity is inevitable and as a result must be managed more prudently and strategically. It’s really all about creating better balance between the scientific objectives of the protocol and the executional objectives, which are becoming far more important for companies.”


-By Gienna Shaw