Former FDA Inspector Notes From the Field: It’s a Compliance Jungle Out There
Considering that clinical trial compliance responsibility is on the Principal Investigator, your contracted participation should add value. Contract Research Organizations (CROs) and independent Monitors must honor the contractual commitments by documenting site deviations and issuing data correction forms. For fiscal year 2010, Monitor inspections by FDA determined that fifty percent (50%) were not in compliance. Twelve percent were classified as official action indicated for warning letter or worse. I will provide analysis of the fiscal year 2011 numbers when they are released.
Meantime, I helped generate these numbers while at FDA in 2010. The most common compliance deficiencies listed were:
- Inadequate monitoring
- Failure to bring investigators into compliance
- Inadequate accountability for the investigational product
The rest of the pie chart in the compliance metrics are for IRB’s Principal Investigators, and Bioequivalence inspections by FDA Consumer Safety Officers/Investigators.
I have recently completed many Sponsor generated Quality Assurance audits. I have issued many notable observations of non-compliance. On my most recent audits I have observed serious adverse event reports (SAE’s) had not been reported over the span of years putting the sponsor out of compliance as well (protocol required SAE report within few days). Inclusion and exclusion violations, missing pages of the informed consent form, not following the protocol for three years for all Subjects, data integrity problems, 21 CFR Part 11 electronic records compliance, and failing to bring the site into compliance. Many simple mistakes when detected early and corrected will compound when left unchecked for years.
It may make sense to audit your trial halfway through, and then at the end, or risk throwing out your highest enrollment sight data for lack of protocol adherence. I have to say I recently observed liquid paper/White Out used on source documents for a clinical trial Subject. It has been many years since I have listed that as an observation. The focus must be risk based with primary efficacy end-points and serious adverse event review at the top of every monitor visit.
Then move through to protocol adherence and test article coverage. Training and hiring qualified monitors are key aspects to providing patient safety and regulatory compliant projects. We have our work cut out for us and FDA is not going to review every study or even more than 2% of them domestically. Fifty percent is not a passing number and you do not want to be listed with the rest of the 483 observation forms on the Internet for all to see.