The immense job of monitoring!
I thought I'd have some fun in this whitepaper and talk about what goes wrong in the lives of monitors. Here are some of my favorite "Good grief, what now?" situations they've given me. Later on in the whitepaper I'll give you a PollMonkey address so you can pick your preferred course of action and see how it compares to other peoples.
Subject situations...check all that apply...
 No Lab test
A subject did not get a lab test on their final visit. The investigator says the subject refused because it hurt to have a needle stick. What should you do?
[a] Have the investigator report the deviation in a note to the Regulatory Binder.
[b] Remind the subject of their obligation to finish the study, they were told of the lab tests in the consent.
[c] Have the investigator report the deviation to the IRB.
[d] Make sure the case report form is clear that the data are not available.
 I'm not sick!
You are monitoring a diabetes study. There is a note in one subject's file that they deny having diabetes, even though their blood work shows they do. You think that a patient who denies having a disease is not a good candidate for a study on that disease. As the monitor, what would you recommend to your boss?
[a] The investigator exit the subject from the study.
[b] The subject be educated about diabetes.
[c] Let the subject complete the study and use the data.
[d] Let the subject complete the study and don't use the data.
Date Wheels Are Useful for Planning Study Schedules
This week I had to estimate a timeline for a study. I wrote the task list and estimated the duration for each task. Then I used the date wheel to estimate the initiation date like this:
Receive firm assignment—Day 0, Jan 8
Write protocol—5 weeks, Feb 12
Submit to IRB—3 weeks, Mar 5
IRB review and approval—12 weeks, May 27
Study initiation—begin May 28
Date Wheels are circular, pocket-sized, calendars used to identify some future date (e.g. when the kittens are due.) Ours are 3.75 inches in diameter, fit easily into your pocket, are flexible, water-proof, and precision-printed for clear, crisp lettering. Don't plan a study schedule without one. Buy them here.
Investigator incidents...check all that apply...
 When did they sign?
The subject and the witness signed the informed consent six days later than the investigator. The visit date, accountability log, screening logs and source notes agree with the doctor's date. You suspect the investigator forgot to get the subject's signature on treatment day. As the monitor, what do you do now?
[a] Confront investigator to get the truth of the matter, and then make a note to file.
[b] The investigator used an investigational device without the patient's consent; it should be reported to the IRB within 5 days.
[c] Have the investigator correct the data and initial the change.
 The case of the missing consent
Just before implantation the investigator turns to an assistant to confirm the patient has signed the consent form. But there is no consent form to be found. The investigator is certain he had the patient sign the form and implants the investigational device anyway. Later, he cannot find a signed consent anywhere. As the monitor, what should you do?
[a] Confirm the investigator reports to the IRB that a subject has been enrolled without consent.
[b] Remind your management that they have five days to report the incident to FDA.
[c] Confirm the patient/subject is truthfully informed of the situation.
[d] Ascertain if the patient/subject was orally informed of the study before surgery.
[e] All of the above
 Fake documents
While monitoring a subject's six-month follow-up data you notice the source document looks fake. All the progress notes are written with the same pen and same handwriting, and the entries slant to the right as you move down the page. You remember monitoring the three-month data and the source documents were real. When you confront the study nurse she confesses that they lost the patient's chart and had to reconstruct it. "We think it was shredded." Can you use the six-month data?
[c] not sure
Begin another advertisement
Adverse Event Definitions: At Your Fingertips
The Adverse Event mousepad/notepad puts complicated adverse event definitions at your fingertips. Use it as a mousepad and find the definitions quickly as you craft a protocol. Use it as a notepad and find the definitions quickly in a meeting.
Starting at the center, you identify the event's characteristics in a pie-wedge. The outer ring identifies the event by type. ISO and FDA definitions are on the right. The tool helps you think your way through the reporting process. Order me.
IRB antics...check all that apply...
 Summaries only, please
The IRB of a famous research hospital refuses to review the full protocol for your non-significant risk study. "We only review summaries of NSR device studies," they say, even though their website procedures state they always review full protocols. You balk, but the IRB stands firm and sends a letter approving the study. What should you do?
[a] Tell the FDA.
[b] Report the incident to AAHRPP, the hospital's research accrediting association.
[c] Stop resisting and initiate the study.
[d] Include a note of objection in your monitoring report.
 Annual renewal
The investigator neglected to get an annual renewal from the IRB and continued to enroll subjects in the study. The investigator claims the IRB never notified him that the approval was up, as they are supposed to do. What "offenses" have been committed?
[a] Subjects were enrolled in an unapproved study.
[b] An investigator failed to file an annual report to the IRB.
[c] The IRB failed to conduct continuing review of research.
[d] The sponsor failed to secure investigator compliance.
Sponsor snarls...check all that apply.
 Anonymous letters
Your manager writes letters to FDA with no return address, seals them, and asks you to mail them from whatever city you are traveling to. You suspect he may be tattling on some questionable practices by your competitors. Are you participating in an unethical practice?
[c] don't know
 Where's the data?
Your company used paper CRFs printed and assembled by a copy shop. When the study is over the data center notices that a page was missing from ~30% of the forms. Of course it's the page with the pivotal, success or failure question on it. What would you recommend as the best course of action?
[a] Have the statistician impute the values based on the values from the other subjects.
[b] Drop the subjects with the missing data from the success/failure analysis.
[c] Continue the study and replace the subjects with the missing data.
If you liked the whitepaper, take the workshop
If you liked this whitepaper, then take the upcoming workshop. We'll review the poll consensus and I'll add my opinions to the mix. The learning objective is to review the skills of monitoring in order to help assure quality in clinical trials. In this intermediate level course participants are expected to have a basic knowledge of clinical research and device regulations. Sign up here or phone us at 773-489-5706.
A quiz, of course
The five-hour workshop is followed by a half-hour online quiz, taken on your own time within the following two weeks. The quiz is designed to test your learning of the concepts discussed in the lecture and your ability to apply those concepts to real-life issues.
You will receive, we will discuss
[x] Printable PowerPoint slides.
[x] Clear example distinguishing intended use, indications, claims and warning.
[x] Selected monitoring procedures and templates.
[x] Recent monitoring warning letters.
[x] A graded quiz with immediate test results.
[x] Certificate of Attendance and 0.55 CEUs.
[x] One computer connection for one learner (each learner must log-in individually).
[x] A copy of the CRA Handbook 2010 (electronic) with registration by October 13.
Who should attend
[x] Clinical research associates.
[x] Managers and directors of clinical research.
[x] Start-up companies planning their first clinical trial.
Dr. Nancy J Stark is President and Founder of Clinical Device Group, a CRO and consulting firm that has been in business since 1990. Her curriculum vitae can be found at www.nancystark.com.
[x] Personal computer.
[x] Internet Access.
Date, time, registration
The 5 hour workshop will be presented on Wednesday, 20 October 2010, at 11:00 Central Time. Event materials will be distributed the day before the workshop. Sign up at here or phone us at 773-489-5706.
Nancy J Stark, PhD
President, Clinical Device Group Inc