Compliance In Focus

Making sense of the many clinical research trial acronyms sometimes feels like swimming in alphabet soup.

After you've been in the field for some time, using these abbreviations often becomes second nature. But for those who are new to this industry, understanding these clinical research acronyms can seem daunting. 

If you need help decoding them, we're here to help. Here are 30 acronyms commonly used in clinical research and what they mean. 

During a training module this week, a group of monitors were discussing the importance of back-up coverage. Monitors that are conducting visits in the field know that juggling schedules can be very challenging. To provide thorough and consistent monitoring, experienced monitors are assigned to a clinical trial or a study team. Next, training is extended into the therapeutic area of research and sponsor specific trainings including SOPs and monitoring plans.  But what about back-up coordinators- are they trained and ready?

In the realm of clinical research, two functions often work together to complement each other to create an additive impact on the overall quality and integrity of a clinical trial. The two functions are clinical monitoring and auditing. But how do these work hand-in-hand, and how are they different?

As monitors, we spend a decent amount of time preparing for the visit – before we even head out the door. On the road, we’ve noticed that the most effective coordinators tend to be those who also prepare for the visit. Spending an extra hour or two before the visit can decrease the amount of queries, follow-up items and even the length of the visit itself. Before your next monitoring visit, consider asking yourself these five questions:

We’re often asked- What makes a good monitor? What’s involved in the day-to-day of being a CRA? Well, it’s no secret that a good monitor often wears and juggles many hats; from reporter, to auditor, to traveler. And like many with this New Year quickly unfolding there are some resolutions from those that live out the day-to-day of clinical research monitoring:

In the realm of clinical research, two functions often work together to complement each other to create an additive impact on the overall quality and integrity of a clinical trial. The two functions are clinical monitoring and auditing. But how do these work hand-in-hand, and how are they different?

When the words “Clinical Research Trial” are heard, many questions may come to one’s mind. What is being tested?  What is involved? Where will it be taking place? Who came up with the trial? Who is paying for it? What doctors are participating? Many of these answers for an Investigational Device (IDE) clinical research trial can be found on ClinicalTrals.gov.

Over the years, we have had many conversations with sponsors regarding their needs for monitoring support services.  It is clear that while many sponsors consider the outsourcing of their monitoring needs to a CRO, they have many concerns that they have shared with us.

While procedures, checklists, guidance documents, report templates and all sorts of other things combine to form the infrastructure for monitoring, what is possibly even more important is the shared mindset.  The acceptance by all that regardless of the title, there is a shared responsibility in calling out issues, in looking purposefully at this document, in questioning that blank.

Monitors that perform their job at a high level can drive the growth and reputation of their company. The companies that employ these monitors are equipped to meet the needs of their clients and ensure that patient safety and data integrity are maximized.

For a sponsor or investigator, selecting the right Contract Research Organization (CRO) to help with the monitoring and management of a clinical trial can be crucial to a successful outcome.

In the realm of clinical research, two functions often work together to complement each other to create an additive impact on the overall quality and integrity of a clinical trial. The two functions are clinical monitoring and auditing. But how do these work hand-in-hand, and how are they different?

It is usually not very difficult to engage sites who have been chosen to participate in a clinical study at the beginning of the trial.  This is an exciting time for any site that is able to bring that new experimental drug or device to their patients who are able to participate in the study!  Many times, during the enrollment phase of the study, sites continue to be excited and active in their roles, and this is usually facilitated by sponsors who are actively encouraging their sites to enroll subjects.

As monitors we sort of live by this motto and we always try to remind our sites of this, we do so in order to help protect the subjects, their site, and the Sponsor of the study all at the same time.

Over the past seven years I have traveled all over the United States and Canada and have even been to Japan once.  Due to the great distance, airplane has been the most expedient method for me to travel.  Given that, I have looked out of hundreds of airplane windows and am always enamored with the view.  I never tire of trying to identify where I am, especially as I get closer to Cleveland Hopkins International Airport.  I only live about 25 miles from the airport and really, how hard can it be to find a landmark from the sky?  For whatever reason, I have the hardest time trying to do this.  So you can imagine my aggravation when my husband accompanied me on a trip a few years back and on our decent into the airport he started to rattle off all of these landmarks and our location.  Did I mention my husband has flown in an airplane about six times in his entire life?  After I was done being aggravated at his skill, I really enjoyed finding landmarks, too.  It was so easy once someone gave me a starting point.  Wearing your ‘auditor’s hat’ during your monitoring visits can be just as easy and fun.  You just need to have the right starting point and tools.

Frequently, by the time a monitor or CRO is brought into a clinical research study, the protocol, case report forms, and informed consent template have been finalized.  As noted in 21 CRF Part 812.42, the sponsor is required to have all study documents approved by the participating institution’s IRB.  As the sponsor is working to create their informed consent document, they likely reference 21 CFR Part 50, specifically incorporating all of the required elements of informed consent into their template.

In general, most hospitals and clinics use electronic medical records (EMR), or a mix of electronic and paper medical records.  Often paper records are scanned into the EMR in order to house all records for a particular patient in one location.

IMARC Monitors sometimes have a challenging job; they are often on the road, trying to balance work and home life.  They juggle multiple studies from different Sponsors, have many relationships to maintain, sites to visit, and reports to write.  At IMARC we want to always provide the very best monitoring services we can.  In order to do that we must have great monitors on staff, so, what makes a great Monitor?

IMARC monitors are all over North America on a weekly basis traveling to a wide range of sites from the small community hospital to the large medical center that also serves as a teaching institution. What makes a periodic monitoring visit a Good Visit? To those in the medical field, they may determine a good visit by the notability or prestigiousness of the facility itself. To the general population in the outside world, they may say - destination. After all, who wouldn’t want to be monitoring at the site next to the sunny, beautiful beach in southern Florida versus next to the corn field out in no man’s land? If you ask an insider, a monitor, the response would sound something like- “That visit was great. The research coordinator – she (he) was a ROCK STAR!” 

As a Master’s of Public Health student at Emory University, one of the most intriguing ideas I encountered was that of upstream prevention. This concept is often illustrated by a metaphor involving drowning bodies in a river; a panic ensues at the riverfront as rescuers eagerly jump in to save the drowning victims. Although many people are saved, the rescue team can’t keep up with the sheer number of victims. One member of the rescue team (the public health expert) decides to travel upstream to find the cause of the problem. Although this member of the team is harshly criticized for abandoning the immediate rescue effort, he is later praised for identifying the source of the problem and preventing many deaths.

It is a common question that follows an informed consent document revision- does the subject need to re-sign? The answer could be yes or no depending on the type of revision that was made to the document. 

Recently, my inbox has been inundated with training opportunities for Risk-Based Monitoring.  Since the FDA’s release of its latest guidance on monitoring in August 2011, the pharmaceutical and device industries have made this a hot topic of discussion.  It seems the term, Risk-Based Monitoring, in spite of the guidance, has become an obstacle.  What is Risk-Based Monitoring?  And what is causing the confusion?  Perhaps the clearest definition for Risk-Based Monitoring was given by a presenter at the Global ACRP Conference this year in Tampa.  She referred to it as “Intelligent Monitoring”.  That says it all, doesn’t it?  Visually, I see the AT&T Commercial (It’s Not Complicated “Infinity”) with all the kids sitting around a table discussing big numbers with a grown-up.  When a little girl responds “Infinity times infinity” the grown man responds by motioning that his head just burst.

While procedures, checklists, guidance documents, report templates and all sorts of other things combine to form the infrastructure for monitoring, what is possibly even more important is the shared mindset.  The acceptance by all that regardless of the title, there is a shared responsibility in calling out issues, in looking purposefully at this document, in questioning that blank. 

It just depends!

As monitors, we spend a decent amount of time preparing for the visit – before we even head out the door. On the road, we’ve noticed that the most effective coordinators tend to be those who also prepare for the visit. Spending an extra hour or two before the visit can decrease the amount of queries, follow-up items and even the length of the visit itself. Before your next monitoring visit, consider asking yourself these five questions:

Deviations from the protocol, or non-compliances, are inevitable across a multi-centered study. Some deviations can be prevented by the investigational site study staff, such as in exclusionary criteria noted in the medical history. Other deviations, such as missed visits due to the subject’s schedule, can not be avoided. According to 21 CFR 812.46(a), it is the responsibility of the sponsor to ensure that the selected investigators are compliant with any conditions of approval of the reviewing IRB. The investigator, according to 21 CRF 812.110 (b), is responsible for conducting the trial in compliance with the conditions of approval of the reviewing IRB. Additionally, investigators are responsible for maintaining records relating to deviations, including dates of and reasons for, according to 21 CFR 812.140(a)(4).

Recently, a team of IMARC monitors traveled to a sponsor’s clinical research headquarters to meet face-to-face, study team to study team, to kick off a new medical device study. The two teams joined together with a heavy agenda to get the study’s ducks in a row prior to our monitors hitting the road for the on-site initiation visits scheduled in the upcoming weeks. While this is not always the case at study start-up, with tight timelines and limited budgets, there are many advantages to getting the teams together at the beginning of the study to help prepare for a successful study. Additionally, the teams can process through potential study challenges before they become potentially larger issues. Read on to learn five reasons why the sponsor should meet with and include the CRO in study start up!

IMARC clinical monitors are constantly on the go monitoring in the field, from California to Connecticut, Vancouver to Miami.  The monitors are no strangers to airport security lanes and the Transportation Security Administration agents (TSA).  Some may even creatively compare monitors to TSA agents. Both groups of people are required to be familiar with federal regulations. The regulations exist to allow for monitors and TSA agents to execute their primary role; ensuring safety. Monitors ensure the safety of subjects in clinical trials and ensure compliance to 21 CFR 812 (device) or 21 CFR 312 (drug). TSA agents ensure safety of travelers and flight staff as well as ensure compliance with FAA regulations.

What is the ultimate goal for every clinical trial?  High-Quality Data that proves safety and/or efficacy endpoints while safeguarding clinical trial participants. How can data integrity be ensured? This requires a combination of a few key players during the course of a study.

While procedures, checklists, guidance documents, report templates and all sorts of other things combine to form the infrastructure for monitoring, what is possibly even more important is the shared mindset of those on a clinical research team.  The acceptance by all that regardless of the title, there is a shared responsibility in calling out issues, in looking purposefully at this document, in questioning that blank to facilitate running a well controlled, compliant clinical trial.

Clinical Research Monitoring is a vital part of the Clinical Trial process, and one of the most prominent skills you’ll find in an effective monitor is exceptional communication.  Whether you’re contacting a site, writing a confirmation letter, drafting a report, or talking to an investigator, your communication skills, or lack thereof, will determine how well you are perceived and will ultimately affect your effectiveness in the clinical trial process.

Many believe good monitoring should heavily focus on Source Data Verification (SDV), which stripped down to its simplest meaning equates to “X=X” and “Y=Y”.  And maybe some of you reading this are thinking “Isn’t that exactly what monitoring is?”  While data integrity is absolutely essential, it is only the beginning of what comprehensive monitoring encompasses.

We’re often asked- What makes a good monitor? What’s involved in the day-to-day of being a CRA? Well, it’s no secret that a good monitor often wears and juggles many hats; from reporter, to auditor, to traveler. And like many with this New Year quickly unfolding there are some resolutions from those that live out the day-to-day of clinical research monitoring:

We call it providing a "Third Set of Eyes."  Interestingly enough, most IMARC monitors have a background in nursing, or as research coordinators. It may very well be that this experience has assisted us in monitoring to empathize with each subject. After all, so many years were spent one-on-one with patients; we see them as individuals- not just subject numbers.

You may have heard the term Sponsor-Investigator before, but just who are they and what do they do?  Just as the title suggests, a Sponsor-Investigator is someone who both initiates (sponsors) and conducts (investigator) an investigation.  This may sound simple, but in actuality, the role can be quite complicated.  However, like anything else, with proper preparation and support it can be accomplished.  Sponsor-Investigators are a rare breed of extremely intelligent, hardworking people who are on the cutting edge of scientific advancement in their respective fields.  They are so committed that they are willing to do essentially twice the work to bring new technologies and advancements to the medical community.

According to 21 CFR 812.110 an Investigator is responsible for conducting an investigation in accordance with the signed agreement with the sponsor, the investigational plan, this part and other applicable FDA regulations, and any conditions of approval imposed by an IRB or FDA.

As questioned in this issue of the Journal of Clinical Research Best Practices - why does the clinical research industry have such a high turnover rate for clinical research personnel?

During a recent monitoring visit, I came across a scenario that challenged my efforts to ensure compliance with the Institutional Review Board’s (IRB) policies.  For background, an East Coast University/Hospital has a new area of outsourcing for the studies that are being conducted at their institution. The local IRB reviews all Phase I/ II studies and all studies that are funded by the National Institutes of Health (NIH). Phase III and IV trials are outsourced to a central IRB.

This blog was written by a newer monitor with IMARC Research.  This is her experience, and certainly not representative of all research coordinators and monitors.  We thank her for sharing this, and hope others who have made the similar transition will chime in with their experiences!

Oftentimes when one thinks of clinical trial monitoring, he thinks of a monitor making periodic site visits to the hospital or institution where the trial is taking place.  During these visits, the monitor verifies the data collected with the site’s source data and study documentation, among other duties.  These periodic site visits are often scheduled and made on an elapsed duration.  For example, some sponsors/studies require a monitor to be on site every 4-6 weeks to keep tabs on the data.  Seems like a pretty straightforward, streamlined, routine process, right?