Kenneth A. Getz
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According to clinical investigators, it's ugly out there! Investigators and site staff consistently report that managing site
operations is difficult—particularly maintaining positive cash flow and profitability. Lead generation has intensified as
competition for new study grants has increased. Study protocols have become more complicated and demanding. Patient recruitment
and retention challenges have escalated. And the burden of regulatory compliance has become onerous and extremely frustrating.
Indeed, in recent interviews with clinical investigators, regulatory compliance is one of the top burdens that sites face
today. Many argue that compliance requirements place unreasonable demands on study staff time and focus, and may, ultimately,
undermine study conduct performance.
"It's not clear if sponsors have even noticed the connection between mounting compliance paperwork and the low morale and
steady exodus of good investigators from clinical research," lamented one New Jersey–based investigator.
The results of a recent study by the Tufts Center for the Study of Drug Development are consistent with these observations.
Turnover among clinical investigators is at an all time high; and the majority of those dropping out of clinical research
are experienced, community-based investigators—not novice investigators, as is commonly believed. Interviews with clinical investigators reveal that there is much to gripe about. Top site concerns offer research sponsors
insight into areas where intervention and assistance might improve study conduct performance.
Besieged by safety reports
One of the largest problems relates to the way Investigational New Drug (IND) Safety Reports are handled. Food and Drug Administration
(FDA) regulations require that all investigators and institutional review boards (IRBs) involved in a clinical study be informed
about any associated severe adverse event (SAE) that occurs anywhere in the world.
"That's a lot of reports," noted Jim Maloy, MD, executive vice president with Drug Research and Analysis in Montgomery, AL.
"One global cardiac study for which we enrolled one patient had 400 IND Safety Reports submitted to the IRB."
"And the information isn't particularly useful. If a study is blinded, recipients have no way of knowing if the SAE was connected
to the actual study drug, a comparator drug, or a placebo," added Maloy. "The reports also don't indicate how many patients
experienced the SAE. I have yet to see a local IRB change a protocol or ask for a change in the consent form based on [IND]
Safety Reports, and I've been involved in a thousand studies," he said. If an SAE is severe enough to warrant such changes,
they're generally made before an IND Safety Report gets issued.
"The problem is compounded if a central IRB is involved," said Jed Ervin, MD, founder and president of the Center for Pharmaceutical
Research in Kansas City, MO. "Central IRBs receive dozens of copies of each IND Safety Report, reviewed and signed by individual
investigators."
Reconsent and disclosures
"But more time consuming and bothersome for sites," added Ervin, "is the requirement that they go back through the entire
consenting process, inclusive of IRB approval, whenever an amendment is made to the study protocol." For a single study, at
least two or three amendments are not unusual. "Reconsenting annoys patients and creates an ethical problem if they're asked
to retroactively agree to changes once the study has ended—a disturbingly common occurrence," he explained.
"Financial disclosure forms represent another big headache, especially for private research operations that provide administrative
support to subinvestigators at disparate locations around town," said Maloy. "Federal regulations require that the forms be
signed by all investigators at the beginning and end of a study and a year after study completion. Yet conflicts of interest
are almost solely a problem in academia where the results of government-sponsored research get commercialized."
