Investigator Responsibilities: Compare & Contrast-FDA & ISO
What to Expect of Your Investigator An
e-Conference by Dr. John Pandolfino & Dr. Nancy J Stark AvailableOnDemand or on CD
Investigators are expected to make certain contributions to
clinical investigations. But there are also many duties they typically take
on that are not identified in any regulation or guidance. Some are standard
practice, others are bad ideas. So what should we reasonably expect from
investigators? Which of the following tasks is not a common investigator
 Supervise all testing of the device.
 Completing case report forms.
 Tell the IRB about non-compliances.
 Maintain a record of device exposure.
 Repair a device that isn't working.
If you answered 2, you know your standard investigative site
practices. Investigators rarely transcribe information from source files to
case report forms themselves. In fact, the best investigative sites have
research nurses who are trained in good clinical practices and who
transcribe data, maintain documentation, and much more.
If you answered 5, you are correct, device repairs are not a
common investigator duty. I have had investigators 'fix' the solder on an
electronic unit and had to find a way to draw a better boundary between
device investigation and device development.
The issues addressed in the guidance document are: 1)
delegation of tasks, 2) study staff training, 3) study staff supervision,
4) oversight of other parties, 5) reasonable medical care for injured
subjects, 6) reasonable access to care for all subjects, and 7) protocol
compliance. There is little that is new in the guidance document, with the
exception of investigators being held responsible for supervising a
sponsor's field monitors.
What else can you expect?
Investigators are asked to do so much more than what's listed in the
guidance document. The very day-to-day implementation of the study is in
their hands. Without their enthusiastic support, a study will stall and
Communication with the IRB
Typically investigators talk to IRBs and sponsors talk to investigators.
Even when a sponsor is responsible to assure a communication has been
delivered to an IRB, the line of communication is through the investigator.
Investigators are responsible for obtaining initial IRB approval, obtaining
approval for amendments to the protocol, obtaining approval for changes to
the device design, for reporting adverse device effect reports, protocol or
regulatory non-compliances, for annual reports, and for final reports.
Last year a well-known IRB refused to review the full text of
an medical device protocol, just because the study was nonsignificant risk.
I could not persuade the investigator to insist on full IRB review. Do you
think this placed the data in jeopardy? Or was the IRB correct: NSR studies
are held to a lower standard.
Communication with the subject
Investigators are responsible for determining if they have access to enough
subjects. They should not conduct two studies at the same time that compete
for the same subject, it introduces bias because the sponsor that pays the
most gets subjects first. It is perfectly reasonable to ask an investigator
outright if they are conducting competing studies.
Only investigators or other persons authorized by the IRB may
approach patients for entry into a trial. A log should be kept of every
patient approached (i.e., screened). If the patient gives consent and
enters a trial they are assigned an ID number, if not, the reason for
non-entry is recorded. Too many reasons like 'subject did not meet entrance
criteria' is a tip-off that the investigator is approaching anyone just to
meet a screening goal. The log should use sequential numbers and every
number should be accounted for. When screening IDs skip from patient 13 to
patient 17, FDA will question what happened to patients 14, 15, and 16.
Communication with the sponsor
We expect investigators to give us honest feedback about a device: how does
it handle, how can it be improved, how does it compare to other
devices—even when we don't ask overtly on the case report forms. We expect
them to inform us about adverse events and non-compliances and to report
them in a timely manner to the IRB. We expect them to be knowledgeable
about the regulations and to promote compliance. We expect them to maintain
good documentation, to allow monitoring, auditing, and inspections.
And, as sponsors, we should expect to pay a fair and
competitive amount for services rendered. The most frequent relationship I
have seen for bad investigator behavior is underpayment. Twenty years ago
the device industry thought that investigators were so lucky to be
investigating our devices that they didn't need to be paid. That day has
passed, and everyone deserves fair remuneration for work performed.
contrast: FDA guidance to the international standard A detailed
cross-functional matrix shows that the 2009 FDA guidance and the 2010
ISO/DIS 14155 standard are very similar in their expectations of
investigators. There are some interesting additions to the ISO/DIS standard
that don't appear in US regulations:1) inform the subject about any adverse events
they have experienced, 2) inform subjects of significant new findings, 3)
maintain and calibrate equipment, 4) ensure accuracy of case report forms,
5) allow sponsor to perform monitoring visits, 6) report all adverse events, not just adverse device effects, and 6) sign the
aside from these few, albeit significant, differences—I find the spirit of
responsibilities to be uncannily similar.
Learn more: take the e-conference I've just touched the tip of the iceberg with regard to
what investigators do. What is the objective of this e-conference? To learn
the subtleties of investigator responsibilities, learn how sponsors can
help assure investigator compliance, and see how the States compare with
The first half of the presentation will be
a discussion of the FDA guidance document given by a bona fide medical
device investigator. The second half will be a comparison to the ISO/DIS
14155 standard, given by a bona fide medical device CRO.
You will receive
[x] PowerPoint slides.
[x] The expertise of a prominent medical device investigator, Dr. John
Pandolfino. [x] Some additional input from Dr. Nancy J Stark. [x] A cross-functional table which compares and contrasts FDA and ISO. [x] Chance for Q&A.
[x] CEUs and certificate of attendance. [x] Please
purchase your own copy of ISO/DIS 14155 atwww.iso.org.
Who should attend
[x] Anyone who's sponsoring a device trial.
[x] Anyone who's an investigator for a device trial.
[x] Regulatory professionals who submit final reports to FDA.
[x] FDA personnel who inspect investigational sites.
[x] Marketers or managers who select investigators.
John Pandolfino, MD is an Associate Professor of Medicine at the Feinberg
School of Medicine at Northwestern University. His career is focused on
clinical and physiologic research of esophageal diseases and he is
currently NIH funded to study the pathogenesis of GERD and Dysphagia. He
has also been involved in the development of new technologies for diagnosis
and treatment of GERD. In addition, he has been the primary investigator on
a number of Industry funded projects ranging from investigator initiated
physiologic studies to clinical trials involving new antisecretory
medications and medical devices (Phase II, III and IV).
His clinical practice focuses on refractory GERD,
post-surgical complications (Nissen Fundoplication/ Obesity Surgery) and
esophageal motor diseases. He is the director of the Motility lab at
Northwestern Memorial Hospital and he also performs a substantial amount of
In-patient consultation at Northwestern Memorial Hospital.
He is editor of Diseases of the Esophagus and is on the
Editorial Boards of Gastroenterology, Neurogastroenterology and Motility,
American Journal of Gastroenterology, Clinical Gastroenterology and
Hepatology. He is an Ad Hoc Reviewer for Alimentary Pharmacology &
Therapeutics and Archives of Internal Medicine. He can be reached at firstname.lastname@example.org.
Dr. Nancy J Stark, PhD and President of Clinical Device Group
can be reached at www.nancystark.com.
System requirements [x] Personal computer. [x] Internet Access. [x] Telephone.
purchase is $424 for OnDemand access and $474 for the CD. Each attendee
is eligible for 0.15 CEUs upon completing the course feedback via the
link provided with the event materials. Click hereto purchase.
Nancy J Stark, PhD
President, Clinical Device Group Inc