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Action Needed if Clinical Trials Are to Be Modernized

By Mari Serebrov
Washington Editor

The FDA got an earful Monday at a hearing on how to best modernize clinical trials and good clinical practice (GCP), but most of the ideas have been on the table for many years, one stakeholder pointed out.

"We need to go big if we are going to modernize clinical trials," Doug Peddicord, executive director of the Association of Clinical Research Organizations, told the FDA. And action, not more research, is needed, he added.

Referencing earlier calls for "research of research," Peddicord claimed such endeavors produce white papers, not transformation of the enterprise. "Knowing is not enough," he said. "We must apply."

As part of its 8-year-old Critical Path Initiative, the FDA has said it's open to clinical trial innovation. While there has been progress in developing the basic building blocks for clinical research, Peddicord noted there has been no improvement in reducing the cost or time involved. The problem is that there's no formalized process whereby industry can bring innovative projects to the agency, he said.

Thus, the industry's natural aversion to risk is blocking innovation. No one wants to go first. "The devil we know can be costly and time-consuming," Peddicord said. "The devil we don't know could be even worse." It could result in a protocol rejection or denied approval.

He suggested the FDA create an agenda for testing innovative clinical trial practices. It could compare current practices with innovative approaches and encourage industry demonstration projects that have the potential to actually save time and money. Many aspects of a clinical trial, including informed consent, could easily be tested, he said.

One way to do that would be to set up an accelerated development pathway that would provide a framework for industry proposals for innovative trial approaches, he said.

But in making any changes to clinical trials, the FDA must ensure it focuses on the needs of the patients, rather than those of the sponsor, investigators, regulators, academic institutions or anyone else involved in the enterprise, Peddicord said.

That sentiment was echoed by Rene Cabral-Daniels, who was representing the National Patient Advocate Foundation and Regulatory Education and Action for Patients.

Safety should not be the FDA's only concern, she said. Instead, it should consider what's in the best interest of the patient. For instance, the agency should look at acceptable risk levels from the patient's perspective. And the benefit to the patient should not be offset by outdated regulatory burdens on the sponsor.

Standardizing many aspects of clinical trials would help reduce that burden and go a long way in making the U.S. more competitive as a place to do clinical trials, Andreas Koester, head of clinical trial innovation at Janssen Pharmaceuticals Inc., a unit of Johnson & Johnson, told the FDA panel.

It also would allow sponsors to focus their limited resources in areas that have potential to impact patient safety and data integrity, he added.

One area that would benefit from standardization is investigator training. Currently, investigators must sit through GCP training every time they participate in a trial with a new sponsor. That can be a frustrating redundancy that discourages physicians from serving as investigators. Some sponsors are tackling the problem on their own – Janssen and Pfizer Inc. now recognize each other's training – but it would be easier if there were a standardized FDA-approved or -endorsed training module, Koester testified.

Speaking to BioWorld Today during a break, Koester said standardized training would reduce participation hurdles for community-based physicians. Their participation is necessary to increase the diversity of trial enrollment and limit the need to conduct studies overseas.

Some of the other recommendations made at the hearing include:

clarifying the safety reporting requirements to reduce the paperwork burden and the noise that can get in the way of the meaningful review of data;

reforming the informed consent process, not just the form itself;

certifying clinical investigators;

recognizing international standards and harmonization efforts;

developing uniform policies with other federal agencies involved in health research;

providing guidance on recruitment materials;

ensuring consistency in the inspection program (device sponsors, especially, have encountered inspectors with a broad range of interpretations, which leads to inconsistency);

recognizing valid clinical evidence from overseas trials, even if they're not FDA-approved;

encouraging the use of centralized institutional review boards;

focusing on endpoints that impact clinical decision-making;

developing a menu of validated tests and biomarkers;

providing a clear regulatory pathway for companion diagnostics;

sharing investigator performance records;

requiring that outcomes and long-term impacts of a study are provided to subjects in plain language;

increasing transparency by not letting contract research organizations audit the studies they conduct.

"A lot of the things you're wishing for are things we think we're doing," the FDA's Bob Temple said in response to some of the suggestions.

The agency will continue to take written comments and recommendations on ways to improve the clinical trial process through May 31.