CDG Whitepapers

Relationship Building in Clinical Trials

A Whitepaper by Dr. Nancy J Stark

Relationship building is an integral part of the successful implementation of any clinical trial. You need good relationships with investigators, study staff, your project team, your colleagues, your boss, and your subordinates in order to successfully implement any project. One thing is for certain: they are not going to change. If you want a good relationship you will have to adapt to them.

Myers and Briggs are great heroines and role models to me. Imagine two women psychologists during World War II. Katherine Cook Briggs and her daughter Isabel Briggs Myers had plenty of obstacles stacked against them. They had only master's degrees, they were women, they were playing in a man's world, yet they developed a personality tool that is still used seventy years later. These two did original research extending Carl Jung's theories to practical applications in the workforce.

Why did it matter? Women were entering the workforce en masse without a clue as to what they would be good at: office work (quiet and peaceful), factory work (noisy and lots of yelling), data work (numbers and logic), design work (color, texture, image, spacial relationships), or whatever.

In this whitepaper I will attempt to adapt the work of Myers and Briggs to the critical task of relationship building in clinical trials. I use layman's language because I am not a psychologist. If you are, feel free to add your comments, corrections, contributions, and rebuttals below.

Jungian Background
The theory of personality type originates from the work of Carl Jung, who proposed that people perceive the world through two different functions: 1) the 'rational' (judging) functions of thinking and feeling, and 2) the 'irrational' (perceiving) functions of sensing and intuition. Jung went on to propose that these functions are expressed in either an introverted or extraverted form. From Jung's original concepts, Myers and Briggs developed their own theory of personality types. [1. Myers-Briggs Type Indicator]

Risk-Based Monitoring for Medical Device Firms on CD

We offer training for medical device firms on risk-based monitoring on CD. The course covers the details of the FDA guidance 'A Risk-Based Approach to Monitoring', recommendations on using it for device studies, includes a sample monitoring plan and template, and features QnA addressing issues unique to device manufacturers. CDs are nice because you can stop and start them, share with your colleagues, and build a library for new hires. The well-researched course is designed and presented by Dr. Nancy J Stark. Click here for more information or call 773-489-5706.

Understanding Personality Types
Myers and Briggs saw that there are four essential steps in how people relate to the world: 1) we focus on the world of our choice, 2) we perceive information, 3) we judge the information, and 4) we present the information to the outer world with a characteristic attitude. We do each of these four steps as either introverts or extroverts for a total of sixteen possibilities. For the sensors among us, I've tried to represent the concept in a simple, colorful visual image. [2. Gifts Differing]

As children we learn how to survive in the world that we know first: family and parents. And those survival skills are our default personality throughout life. As we gain experience and mature we learn to move out of our preferred personality type and become skilled at all possibilities, allowing us to act appropriately in different situations. But when under stress we tend to revert to the survival skills of our childhood. If we understand our own personality types, and become adept at discerning the personality types of others, we can adjust our behavior to build the best possible relationships with our colleagues.

[1] Focusing on the World: Introversion or Extroversion
People prefer to focus on either the inner world of thoughts and ideas (introversion) or the outer world of people and things (extroversion). Introverts do their best work in their heads in reflection; extroverts do their best work in the outside world, in action. Our focus on the world effects dramatically how we live in the world. Only an introvert would sit alone in their office and write this whitepaper. An extrovert will be impatiently waiting to get to the practical applications.

Introverts organize the facts and principles related to a situation and are good at researching material, writing protocols, or designing investigations; extroverts organize the situation itself, including any idle bystanders, to get things rolling. Extroverts are good at implementing clinical investigations.

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Introverts work out their insights slowly and carefully, searching for eternal truths. Extroverts have an urge to communicate and put their inspirations into practice. Can you imagine the annoyance of an introverted study nurse when an extroverted monitor bombards her with emails to give her the latest study updates; or the annoyance of an extroverted (and eager) investigator when an introverted monitor is slow to communicate the start date?

[2] Perception, Taking in Information by Sensing or Intuition
Perception refers to how you get information from the outside world into your head. People take in information either by sensing or by intuition. Sensing means to become aware of information by our five senses: touch, smell, sight, sound, and taste. Intuition means to become aware of information through the unconscious. With intuition we incorporate our ideas or associations to what we sense with lightning speed and seemingly without logic.

Discuss a new device with a sensing person and they may tell you it is too lightweight, it is smaller than the current model, the materials aren't sturdy enough, but the display panel is clear and easy to read—all the information taken in by their senses. Sensing people are well suited for the demands of clinical trial monitoring. Practical and matter-of-fact, they see the world as it is rather than as it should be. They are often good project managers, following the project with Gantt charts, spreadsheets, drawings, flowcharts, and data. If both you and the investigator are sensors you may focus too closely on the details and lose sight of overall progress.

Hand an intuitive person the same device and they may answer, "This reminds me of my grandmother. She used this kind of device every day when I was a kid, we'd check in on her to make sure it was functioning properly and then play a game of checkers." Instead of focusing on the device, your intuitive colleague focused on her associations with it. [3 Tieger]

Intuitive people often have inspired product ideas, clever solutions to problems, or make associations that no one else would see. Intuitive people are good at picking up undercurrents, they know when a situation is 'off' even if they can't exactly tell you why. If both you and your investigator are intuitives, you may have imaginative conversations but not notice some study problems.

I had an extroverted, sensing boss who had a rule that we could present no more than three possibilities to him. If he asked you what went wrong, you had better not give him a list of five things. If he asked you for a recommendation, you had better not have more than three. His intuitive, data-loving subordinates were terrified.

“Readers who are sensors will tend to confine their attention to what is said here on the page... readers who are intuitive are likely to read between and beyond the lines to the possibilities that come to mind.”

[3] Judging, Processing Information by Thinking or Feeling
Judging refers to how you process the information you take in. Thinkers use a logical process aimed at reaching an impersonal finding. Feelers use an emotional process of viewing information in a personal, subjective manner.

The thinking protocol writer may make a list of all the data elements they think are necessary to meet the purpose of the new clinical trial. As they develop the protocol they use their list of data elements as an absolute guide. They are not swayed by pleas from marketing to include questions they have already dismissed as unessential or exclude questions because "it is knowledge we would rather not have." Thinking writers may try to collect too much data in a clinical trial—oblivious to the impracticality.

If, as a member of the project team, you want additional data elements included in the study you should listen closely to the thinking writer's rationale for omitting them, be respectful of their reasoning, and use facts and data that relate back to the trial's purpose to persuade them to make the change. Thinking people objectify situations—dealing in facts, figures and data; they do not respond well to insincere flattery. (My husband is even suspicious of sincere flattery, I only tell him he has done a good thing when I know he already thinks so himself.)

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Our professional monitors are experienced in risk-based monitoring of device studies (because that's how device studies are often done), they know how to work with all personality types, their goal is to worry so you can sleep at night. Our Network Staff has been involved in dozens of device trials and hundreds of issues; their extensive knowledge can solve your problem de jour. Click here to request a proposal for clinical research services from CDG or phone 773-489-5706.

A feeling person may make a list of data elements but it will have little influence on the final protocol design—the decision to collect data is made because it “feels” right. The decision is made first, and a rationale is developed later. A thinking monitor who is ill-at-ease with the site's data collection should be delicate with a feeling investigator who is confident the device works, but they should not back down. They should challenge the data with facts while being thoughtfully respectful of the investigator's mode of processing information.

Another consequence of thinking and feeling personalities is how they relate to each other. Feeling people subjectify situations—anticipating how facts, figures and data will affect the people involved. A feeling monitor (such as myself) might have difficulty enforcing an important requirement, say, for dating an informed consent, because it causes too much inconvenience to the investigator. The feeling person’s prime motivation is harmonious relationships, not regulatory compliance. A sensing boss has no difficulty pointing out the monitor's deficiencies.

“A reader who first considers whether an idea is consistent and logical is using a thinking process. A reader who first considers whether an idea is pleasing or displeasing, supporting or threatening, is using a feeling process.”

[4] Attitude to the World: Perception or Judgment
Our attitude in presenting information to the world is a reflection of which personality type is more strongly developed, perception or judgment. Attitude or "face" refers to how you present information back to the outside world. For extroverts, attitude is a reflection of the personality type that is dominant. For introverts, attitude is a reflection of the personality type that is subordinate because they reserve their favored, dominant preference for the more highly prized, inner world. In other words we know exactly what extroverts think and we never know what introverts think.

People with perceptive attitudes maintain an open mind regarding situations, continuing to seek additional information that can broaden and deepen their understanding. If pressed, they will disclose the facts, but they will refrain from telling you what it means or predicting the outcome. Perceptive people make others feel safe and accepted, and are valued members of any project team because they keep an open mind. Project managers with perception attitudes may be reluctant to move the action forward. They are more likely to delay conclusions or fail to act at all. They can be positively frustrating to bosses who who are at a critical decision-point.

Persons with judging attitudes shut off their perception (at least for the moment) and make a judgment. They may not have all the facts, but they can certainly tell you what they mean. Monitors or project managers with judging attitudes will have strong opinions about the value of a project, work product, piece of data, or whitepaper; and will freely share that opinion with listeners. They are more likely to come to wrong conclusions, a positively frustrating behavior to bosses who want to be sure before acting on a recommendation. But judgers are an essential component of a well-functioning project team; they bring issues to closure and move the project to the next step.

The Queen of Hearts in Lewis Carroll’s classic novel Alice in Wonderland had a typical judgment attitude (as well as being an impatient extrovert). “Off with her head, we’ll have the execution now and the trial later!” she said.

“Readers who are still following this explanation with an open mind are using perception, readers who have decided by now that they agree or disagree with me are using judgment.”

Putting It to Practice
The most important step in building relationships is the first one: know thyself. To help you get over the embarrassment of digging so deep into your psyche, I'll tell you that I am an introverted, sensing, feeling, judger (an ISFJ.) I live in my head, which is far more fascinating to me than anything going on outside; furthermore you will never know what I really think. I take in information by my senses: are there data-gaps, are the facts consistent, do I trust the source, do I need more information? I am a feeler, use the wrong word (mismanagement versus bad economy) and your conversation with me is over. And I am a judger, I have an opinion about almost everything, a quality essential for writing whitepapers or editorials.

Happily we are not stuck on home base. With time and experience I have learned to behave like an extrovert, make a rare intuitive leap of logic, be objective in my assessment of a situation, and withhold judgment until the facts are in—at the cost of a great deal of psychological energy. The hallmark of maturity isn't balance, but being able to move freely from one extreme to the other as the situation demands.

The next step is understanding your colleagues. Changing them is not your goal or your business, and anyway it won't work. The goal is to build relationships that will facilitate the successful completion of your trial. If you're working with an introvert be respectful of their privacy; if you're working with a extrovert enjoy the excitement. If your working with a sensor be prepared with facts and details, if with an intuitive go for the big picture. If your working with a thinker be logical in your presentation, if with a feeler never, never, never say "you". If your working with a perceptive be patient while they work through information on their own, if with a judger you may want to slow them down. The best project teams have someone of every personality type.

Relationships are complicated by supervisor/subordinate, client/consultant, parent/child, wife/husband, boyfriend/girlfriend, addiction, religion, politics, culture, heritage, wealth, and so much more; there is no one simple answer to building good relationships. But understanding personality types and adjusting our own behavior to meet the needs of our colleagues in order to meet the goal, is something we can all do.

References
[1] Myers-Briggs Type Indicator, Wikipedia, the free encyclopedia.
[2] Isabel Briggs Myers with Peter B Myers, Gifts Differing, Understand Personality Type, Davies-Black Publishing, Palo Alto, CA, (1980).
[3] Teiger PD, Barron-Teiger B, The Art of SpeedReading People, Little, Brown & Company, New York (1998).


Questions or Comments?
Please post your questions, comments, contributions, and rebuttals below.

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc

 

 

Risk-Based Monitoring—The New FDA Guidance

An Op-Ed by Dr. Nancy J Stark

FDA's draft guidance, "An Oversight of Clinical Investigations—A Risk-Based Approach to Monitoring" (August 2011) references the ICH-GCPs six times. The ICH-GCPs were written in 1996 by pharmaceutical sponsors and regulators from the US, Europe, and Japan. It is 15 years old and is showing a few signs of age—there is no discussion of central data management or electronic security issues, for example. But because the phrase 'good clinical practice' is in the public domain, ICH was free to adopt it as part of the title of document E6, "Good Clinical Practice: Consolidated Guidance." The Center for Drugs published the guidance in the Federal Register giving it high standing in the regulatory community.

Although used by device manufacturers, the guidance does not work well. It's description of an Investigator's Brochure is chemically-centered not mechanically-centered, investigational devices are stored and dispensed but never installed, there is no mention of training an investigator to use the investigational product, there is no mention of software-controlled devices or software collected data, no mention of caregiver or healthcare provider safety; in other words, for medical devices, the ICH-GCPs are inadequate and out-of-date.

ISO 14155 'Clinical investigation of medical devices in human subjects—Good clinical practice' (2011)—the internationally definitive document for medical device clinical studies—is not mentioned even once; yet the international standard was closely harmonized with ICH-GCP to promote international continuity. I could live with the lack of acknowledgement in FDA's guidance if the same FDA Office hadn't taken such a heavy hand in writing the ISO standard. It is wrong to insist on practice-changing language (such as moment of consent versus moment of enrollment) and then turn your back on the work product as FDA seems to have done.

The draft guidance draws heavily on the ever-increasing presence of electronic data collection. A really cool EDC system can spot a lot of site problems before the human eye ever gets to the data. But these systems are expensive (think in terms of a $1M for a modest study) and unaffordable to small start-ups.

Finally, it was the Offices of Compliance from CDRH, CDER, and CBER who wrote this guidance. While they promise us the inspection manual will be promptly updated to match the guidance, they do not make assurances that the reviewers in the Office of Device Evaluation will follow along. Sponsors are strongly urged to get buy-in on the monitoring plan from reviewers before initiating a clinical trial.

While device manufacturers can use the new guidance to their benefit, often to defend existing practices, they should make certain FDA's Office of Device Evaluation buys into any IDE monitoring plan.

 

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc

Risk-Based Monitoring—The New FDA Guidance

A Whitepaper by Dr. Nancy J Stark

In August of 2011 FDA released a draft guidance document titled "Oversight of Clinical Investigations—A Risk-Based Approach to Monitoring." At first I was very excited because the monitoring guidelines had not been updated since the 1988 "Monitoring of Clinical Investigations." But then, as I began to consider the ramifications of implementing the new guidance for medical device investigations I started to have mixed feelings. The first part of this whitepaper is a factual review of the draft guidance with ideas about how device manufacturer's can take advantage of it. The second part (next blog) is an op-ed expressing my views about what it will mean for the device industry. [1.Risk-Based Monitoring Guidance] [2. Monitoring of Clinical Trials]

Two points stand out as noteworthy before we begin: 1) the draft guidance was written by the Office of Compliance not the Office of Evaluation, and buy-in from an IDE reviewer is uncertain, and 2) the draft guidance addresses itself to drugs with a mere mention of devices as an afterthought, so most concepts have to be 'retrofitted' to device needs.

Part One: Review of Guidance
Risk-Based Monitoring
The draft guidance is based on the premise that most sponsors conduct on-site monitoring visits every 6-8 weeks with the goal of source verifying 100% of the data 100% for 100% of the subjects. It uses this premise to argue that sponsors will save money by moving to risk-based monitoring because such a move will result in fewer monitoring visits. Risk-based monitoring probably will result in fewer on-site visits for big pharmaceutical firms, who may be 'conducting hundreds to thousands of trials in locations around the world'. [3. Quality Management in Clinical Trials] But start-up medical device companies have never monitored as heavily as the guidance assumes and, in that sense, the principles risk-based monitoring won't save on monitoring costs.

The guidance suggests that we use fancy statistical algorithms and analyze real-time data as it comes into electronic data capture systems to identify high-risk sites or high-risk data. The algorithm could be something like 'Risk Priority Number = severity x likelihood of occurrence x detectability'. A Risk Priority Number is calculated for each identified risk. When high-risk sites or data exceed a trigger, they merit immediate, onsite monitoring visits. [3. Quality Management in Clinical Trials]

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Training on risk-based monitoring is now available from CDG! The course covers the details of the FDA guidance 'A Risk-Based Approach to Monitoring', recommendations on using it for device studies, include a sample monitoring plan and template, and features QnA addressing issues unique to device manufacturers. The well-researched course is designed and presented by Dr. Nancy J Stark. Click here for more information or call 773-489-5706.

High risk sites and high risk data
A high-risk site is a site with a high probability of having a problem; the 'symptom' might be that they are enrolling at a slower or faster rate, experiencing a higher or lower rate of adverse events, or having a higher rate of non-compliances than other sites. For example, one site I worked with suddenly stopped enrolling subjects altogether. The sudden change in enrollment pattern should have triggered an on-site monitoring visit. We eventually learned the site had enrolled the same subjects in multiple trials and compromised everyone's data. The site stopped enrolling because they were being audited by other sponsors for fraud.

High-risk data might be a particular type of event or outcome that is a 'symptom' of a problem with the study. For example, a high rate of post-procedure embolism might indicate a poorly trained investigator or a problem with subject selection.

The guidance suggests that any site in the start-up phase of the study is a high-risk site and that on-site monitoring should be performed at every site in the study's early stages.

Device companies can adopt the same principles using low-cost methods. Have the sites fax or scan the case report forms to the monitor once a week for off-site monitoring (i.e. remote monitoring). With one trial and maybe 100 subjects, a monitor can easily examine the case report forms manually for high-risk sites or data without the need for statistical algorithms.

Critical data and processes
Critical data and critical processes are the types of data and processes most likely to be high risk. Critical data include: [1] evidence that the subject really exists, [2] evidence that subject has the disease or condition being studied, [3] evidence that IRB approval was obtained, [4] evidence that informed consent was signed before the intervention or procedure, [5] endpoint data that address the hypothesis, and [6] serious adverse device effect data. For each study you'll need to make a unique list of endpoint data and adverse device effect data that is critical.

Critical processes include [1] the process of obtaining informed consent, [2] the intervention or procedure, [3] timely reporting of regulatory non-compliances or study deviations, [4] timely correspondence with a data safety monitoring board (if one exists), and the like. Because studies vary so much from each other, you'll need to make a unique list of critical processes for each one.

Critical data and processes are most likely to be high risk and should be checked for closely during the off-site monitoring process.

CDG has monitors experienced in risk-based monitoring

Our outsourced monitors come in with the attitude of service, impermanence, and an enthusiasm for the new; they are accustomed to off-site monitoring and problem spotting. They also carry a breadth of experiences that can help solve the issues de jour. Click here to request a proposal for monitoring services from CDG or phone 773-489-5721.

Methods of monitoring
Next the guidance considers two different methods of monitoring; on-site monitoring and 'centralized monitoring', meaning the real-time analysis of data by an application running on a server in some data management center.

I propose that for device studies there are four methods of monitoring: [1] on-site monitoring, [2] off-site monitoring of faxed or scanned case report forms, [3] off-site monitoring of electronic ally captured data, and [4] off-site monitoring of source data that has been captured by the device (usually in vivo or in vitro diagnostic devices.) Often data card is changed out on-site and the data card analyzed off-site. Sometimes the data card may transmit data electronically via the internet—consider a digital camera used to take photographs of the procedure. In the future, of course, it may even be possible to remotely access electronic medical records.

The idea, then, is to use the most expensive method of monitoring (on-site) for sites or data or processes that are critical and high risk and to use less expensive methods of monitoring (off-site or remote) for sites and data that are less so. It is a welcome concept to device manufacturers who are cash-starved and looking for ways to economize.

Triggers
The idea of a trigger is that some server at a data management center somewhere is programmed to alert you if critical data or a critical process has become high-risk; i.e. has the value or frequency of a critical data element or critical process step changed in such a way as to demand attention. Indeed, if hundreds or thousands of sites are reporting data every day, you will need a program to screen the information for anomalies or outliers.

But since most device firms are doing only a few studies at a time, having the case report forms faxed or scanned to the monitor for remote viewing is an inexpensive alternative. The monitor checks the forms for, [1] completeness (no missing data), [2] contemporaneousness, [3] legibility, [4] logic, [5] adverse device effect reports. The forms can be checked for everything except source verification. The monitor issues and resolves queries for any issues observed. Most triggers are found by simple observation.

Then the case report forms are forwarded to the data center where the data are entered into a local (often non-networked) computer. Here the data may be statistically analyzed to see if a site, data element, procedure or process step is at risk and merits an unscheduled, on-site monitoring visit.

Monitoring Plan
A monitoring plan should be developed for every study. This requirement is not new to sponsors conducting IDE studies or European studies under ISO 14155, but the guidance makes clear recommendations for the format. I recommend you develop a template for a separate document that can be referenced in the protocol, and don't make the monitoring plan a part of the protocol itself.

Section One—Study Description
As a separate document, the first section describes the protocol, investigational device, purpose of the study, and other obvious reference information. You need to describe, [1] the monitoring approaches you will use for the study, [2] criteria for determining the timing, frequency, and intensity of planned monitoring activities, [3] specific activities required for each monitoring method employed during the study, including
reference to required tools, logs, or templates, [4] definitions of events or results that trigger changes in planned monitoring activities for a particular clinical investigator, and [5] identification of possible deviations or failures that would be critical to study integrity and how these are to be recorded and reported.

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Sometimes to you want to discuss an issue, but implement the solution yourself. If you want a second opinion about clinical, regulatory, biological safety, or reimbursement strategies, sign us up as consultants. Email us here or call Nancy at 773-489-5721.

Section Two—Reporting
Section two of the monitoring plan should discuss the communication of monitoring results to management, review boards, and regulatory bodies. It should describe the format, content, timing, and archiving requirements for reports and other documentation. For example, if the monitor receives case report forms by fax or email, it makes sense to require, say, a weekly or monthly report. Section two should discuss the process for appropriate communication of the findings to management, review boards, and regulatory bodies.

Section Three—Noncompliances
Section three of the plan should discuss the management of noncompliance. How, and who, will follow up with investigators found to be non-compliant with the regulations, protocol, or IRB requirements? If non-compliances persist will the site be retrained, terminated from the study, or will some other action be taken? If protocol deviations are detected you need a plan for root cause analyses. Problem-solving has always been a part of a monitor's responsibilities in device trials and it may require an on-site visit to really assess the problem. I have had the root cause to be such simple things as the data transcriber needing spectacles, a three-hole punch, or a dedicated phone line. Eyes-on may be the only way to detect such problems so they can be solved.

Section Four—Training
Section four of the monitoring plan should describe specific training for monitors and internal data auditors, especially with the detection of triggers and recommendations for on-site monitoring visits. For device studies, I recommend section four also discuss training plans for investigative site personnel. This section should also describe plans for random quality audits.

Section Five—Amendments to Monitoring Plan
Section five describes the process for amending monitoring plans. What events may require review and revision of the monitoring plan and establish processes to permit timely updates when necessary?

Much of sections Two to Five can be incorporated into the clinical research quality management system. By developing procedures for off-site monitoring you won't have to repeat them in every monitoring plan.

References
[1] 'Oversight of Clinical Investigations—A Risk-Based Approach to Monitoring' FDA, August 2011. http://www.fda.gov/downloads/Drugs/.../Guidances/UCM269919.pdf
[2] 'Guideline for the Monitoring of Clinical Investigations' FDA, January 1988.
[3] 'Quality Management in Clinical Trials', March 2009, Clinical case series from Pfizer.

Good Monitoring Practices—"Good Grief! What Now?"

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...
[1] 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.

[2] 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.

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Investigator incidents...check all that apply...
[3] 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.

[4] 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

[5] 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?
[a] yes
[b] no
[c] not sure

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IRB antics...check all that apply...
[6] 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.

[7] 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.
[8] 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?
[a] yes
[b] no
[c] don't know

[9] 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] Monitors.
[x] Clinical research associates.
[x] Managers and directors of clinical research.
[x] Start-up companies planning their first clinical trial.

Presenter
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.

System requirements
[x] Personal computer.
[x] Internet Access.
[x] Telephone.

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.

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc