Compliance In Focus

A well-controlled clinical trial is much like a well-controlled experiment: They are both rooted in the cornerstone of the scientific method.

Fortunately for sponsors and their research teams, the FDA gives explicit guidance on what it means to run an adequate and well-controlled clinical trial in 21 CFR 314.126. 

Let's take a closer look. 

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?

Gamification is defined as “the process of turning an activity or task into a game or something resembling a game.” This concept has been leveraged in the fields of education and marketing to create engagement with a topic or product by using game playing techniques such as point scoring, achievement badges, or virtual currency.

Please take time to review Emily Haglund’s article “Risk Management in Clinical Research Process and Application” that was recently posted on GxP Lifeline.  The applicable guidances for good clinical practice (GCP), ICH E6 and ISO14155, state explicitly that the sponsor is responsible for quality assurance and quality control. One aspect of quality involves how risks are approached and managed throughout the course of a clinical trial, and is the focus of this article.

On Friday, May 23, 2014 the Federal Register announced a notice that in an effort to increase the quality and efficiency of clinical trials, the Food and Drug Administration (FDA) was planning to grant a one-year, $7,500,000 grant to Duke University’s Translational Medicine Institute (DTMI) (renewable up to a total of five years, $37,500,000). This grant would primarily go to fund the public-private partnership Clinical Trials Transformation Initiative (CTTI).  CTTI  was originally created as a partnership between the FDA and Duke University in 2008, but now includes more than 60 organizations with representatives from government agencies, industry, patient advocacy groups, professional societies, investigator groups, academic institutions, and other interested parties.

Do you know why rules, regulations and standards exist? What exactly is Good Clinical Practice and how does this help protect patients and data integrity?

Often, when one thinks of the team that actually brings a new medical device or drug to market, the first people that come to mind are those at the sponsor company and the investigators at the individual sites – the leaders of the study.  What may be less known, though, is that often the study hinges on the shoulders of the Clinical Research Coordinator (CRC).  Briefly, CRCs are responsible for the accurate maintenance of the records for the trial, as well as many parts of the trial that otherwise may be overlooked.  Some of the major responsibilities of the CRC are:

Recently, the United States Department of Health and Human Services and the National Institute of Health (NIH) issued two proposed rulings that may have a profound impact on how results of clinical trials are made more transparent to the public.  However, before we discuss these proposals, we should discuss briefly how the public has access to clinical trials.

Coming from a background of working as a patient care nurse in the ICU, I would witness the consent process on a daily basis for biopsies, bronchoscopies, chest tubes, arterial lines, etc... These were non-research procedures; they were procedures to assist in the treatment of the critically ill. When I first started a career in research, I already knew that obtaining consent was more than a piece of paper and that it was a discussion and a process, but “a consent is a consent” for standard treatment in a hospital or for research, right? WRONG- I found out very quickly through IMARC’s training program that obtaining consent in research involves so many different specific elements, different from an informed consent for non-research procedures.

When it comes to the Battle of the Sexes you may be surprised to hear this competition is a popular one in the field of health research. On Tuesday, September 22, 2014 the National Institutes of Health (NIH) announced that it will be distributing $10.1 million in grants to scientists and research facilities studying a host of topics, from drug addiction to migraines.  These funds are intended to help support the inclusion of more research subjects, particularly females, in studies that require a little more representation of the XX chromosomes in their laboratory subjects. This means the participation of more female animals, even cell lines, in research laboratories.  The remainder of the awarded money will be used to supplement analysis of gender differences in the studies’ resulting data.

It’s an unfortunate reality in clinical research; Oftentimes sites struggle to recruit subjects.  Frustration trickles down from the principle investigator and on down to the coordinators as sponsors put pressure on sites to enroll, enroll, enroll.  What are the barriers to recruitment and how can they be overcome?

I ran across an interesting article in “The Gray Sheet” on strategies to increase the enrollment of women in clinical trials.  The FDA notes that adequate and appropriate populations of women are needed to support 510(k) clearances and PMAs.

I am often asked by industry colleagues that if I had to pick just one “favorite” federal regulation what would it be?  The answer is easily 21 CFR 812.100, as this regulation embodies 95% of the investigational site non-compliances  I observe as I conduct clinical investigator audits. Let me elaborate.

An article was recently published in the Clinical Researcher entitled “Increasing Provider Engagement in Clinical Research Starts with Research Awareness:  Leveraging Education and Technology to Improve Participation”.  In this article, the authors indicated that whether directly or indirectly involved with clinical trials, increasing research awareness may increase health outcomes, study accrual, and patient safety.  Subsequently, the ability to enroll in a clinical research trial may improve patient care for some individuals and result in better outcomes for future patients.  Without increasing accrual, sites and sponsors are not able to efficiently conduct clinical trials.

MYTH 1: My doctor wouldn’t have told me about the clinical trial if he/she didn’t think it was in my best interest

Advancements are always being sought out to improve clinical research administration, with better patient care as the ultimate goal.  According to an article on The Association of Academic Health Centers website, the current administrative landscape for clinical trials is exceedingly complex.  Many interdependent functions are spread across the research enterprise, which often results in the establishment of administrative structures and small bureaucracies operating as separate, unconnected silos that lack policies or formal procedures for communications and interaction.  The article goes on to explain that the life cycle of a clinical research project involves stakeholders from different realms of academic health center administration who possess various skills and knowledge about clinical research or business functions.

Most of us have been there before.  In an attempt to get that last item completed before the end of another long day on the job in the field of clinical research we inadvertently scribe the wrong date on the research record we are completing.  We are all human after all, and mistakes do happen from time to time.  Sometimes we know instantly and can correct ourselves, and others someone else points out the discrepancy that we may have over looked.  It’s how we respond after we are made aware that we have made the mistake that I want to focus on for this blog post because there are multiple different options one can take.

We ran across an interview with Owen Faris in The Gray Sheet, acting clinical trials director for CDRH.  The position was established to help implement the several CDRH strategic priorities in 2014-15 that were announced in February focusing on speeding up the IDE review process and encouraging more IDE trials in the U.S.

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.

Currently hypertension affects 30.4% of the American population and is projected to cost the nation 91.4 billion dollars a year in 2015.  A subset of hypertensive patients have what is referred to as resistant hypertension.  This refers to a patient receiving three or more anti-hypertensive medications without receiving adequate benefit.  Because of this arbitrary definition, the number of people afflicted with resistant hypertension has varied between 5% in general medical practice and 50% in nephrology clinics. As an alternative to additional anti-hypertensive medication, renal denervation has been used as a therapy to combat high blood pressure.

In a clinical research, patients are the most important key to a study. Subject retention is vital for data integrity, and lack of subject participation can have costly delays for the Sponsor.  Since research sites spend a great deal of time and effort finding qualified subjects, they should also be equipped with reasons subjects withdraw to help prevent this from happening.

Monitoring clinical trials at a high level requires a unique set of traits, skills, and abilities. While monitors often have diverse backgrounds and experiences, there are specific attributes that characterize great monitors and separate them from the rest of the pack. The following list identifies those attributes and explains why each is instrumental to clinical monitoring. This list is not ranked in any particular order and is not meant to be all inclusive; please share your thoughts!

I came across an article describing the benefits to having a shortened informed consent form.  As a monitor who has had experience with reviewing informed consents, as well as a former research coordinator who has obtained consent from study participants, I have mixed feelings on the topic.

You may be familiar with IMARC Research’s History of Clinical Research (HCR).  We recently released an eBook about it that briefly describes all of the images that currently make up the timeline.  If you have visited our office, you may have also been given a guided tour of one of our most renowned resources.  Due to the overwhelmingly positive feedback we have received, we will be highlighting each time point with a series of blogs that we plan to release over the course of the 2014 calendar year.

Do you know why rules, regulations and standards exist? What exactly is Good Clinical Practice and how does this help protect patients and data integrity?

Oftentimes there are questions about doing research with medical devices (as opposed to pharmaceuticals).  We recently highlighted in our whitepaper on the differences (and similarities) of doing research with drugs vs. devices, and also have an infographic summarizing the main points.

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?

When conducting clinical trials, it is of utmost importance that the data generated be free from threats to the validity and integrity of the research. As demonstrated in many FDA warning letters, a commonly cited source of bias in clinical research can be found in the financial ties between investigators and sponsors. It is not unusual for the innovations of individual physician investigators to receive research and development funding from larger organizations that possess the resources to bring these innovations to market, and under 21 CFR 54, it is the responsibility of sponsors to collect for each investigator who is not a full-or part-time employee either a certification of no financial conflict of interest (Form FDA 3454), or a disclosure of the financial arrangements between the sponsor and investigator (Form FDA 3455). These financial disclosures must be updated by the investigators if there are any changes in financial disclosure status throughout the study, until one year after the study is completed.

Coming from a background of working as a patient care nurse in the ICU, I would witness the consent process on a daily basis for biopsies, bronchoscopies, chest tubes, arterial lines, etc... These were non-research procedures; they were procedures to assist in the treatment of the critically ill. When I first started a career in research, I already knew that obtaining consent was more than a piece of paper and that it was a discussion and a process, but “a consent is a consent” for standard treatment in a hospital or for research, right? WRONG- I found out very quickly through IMARC’s training program that obtaining consent in research involves so many different specific elements, different from an informed consent for non-research procedures.

In order for a new medical product to reach patients it must first be proven safe and effective and then be approved for use by the governing regulatory body. Clinical trials are the vehicle to bring these innovative technologies to patients and evaluate them in support of regulatory approval. Unless a product is approved under the appropriate regulations for a specific use, it cannot be commercialized for that indication. In clinical research the products are still investigational, and even in a hospital setting, these products are treated differently.

According to the regulations for clinical trials, the PI is personally responsible for conducting and supervising the conduct of human subjects research by “protecting the rights, safety, and welfare of subject’s under the investigator’s care”.  The PI also has to ensure that all the research he is responsible for is conducted in an ethical manner and in accordance with all federal, state, and local laws and regulations, institutional policies, and the requirements of the IRB. So what exactly is “oversight”?  Oversight is defined in the Webster’s online dictionary as “management by overseeing the performance or operation of a person or group; watchful care, superintendence, general supervision”. As you can imagine, this can be quite an undertaking.

I recently came across this article describing the benefits to having a shortened informed consent form.  As a monitor who has had experience with reviewing informed consents, as well as a former research coordinator who has obtained consent from study participants, I have mixed feelings on the topic.

Today's blog was submitted by guest blogger, Melissa Byrn.  Melissa is affiliated with the Office of Clinical Research at a large academic research organization and will be contributing blogs to IMARC Research.

ICH GCP E6 4.8.3 states that neither the investigator, nor the trial staff, should coerce or unduly influence a subject to participate in a trial, and special care must be taken to assure it is met when dealing with populations whose very nature places them in a situation where they might be more easily coerced or influenced.

You did it!

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?

Today's blog was submitted by guest blogger, Melissa Byrn.  Melissa is affiliated with the Office of Clinical Research at a large academic research organization and will be contributing blogs to IMARC Research.

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 former research coordinator of five years, I am well aware of the extremely busy and highly demanding nature of the job. In addition to balancing multiple trials, subjects, physicians, sponsors, and monitors; coordinators are often required to perform a diverse set of tasks that go beyond the scope of subject visit conduct. This may include regulatory submission and maintenance, laboratory processing and shipping, subject recruiting, and source document creation among others. Furthermore, coordinators often work to facilitate trials across multiple locations and must ensure that studies are conducted in accordance with applicable federal regulations, the investigator agreement or 1572, the protocol, and the rules of the IRB (FAIR SHAKE). Given the multitude of responsibilities, some coordinators may be spread too thin.

Previously, we have discussed the importance of choosing a Contract Research Organization (CRO) for your Cardiovascular (CV) clinical trial that possesses a strong therapeutic background, as well as a strong regulatory foundation. We also acknowledged CROs, in order to be successful with CV clinical trials, must have a powerful knowledge of CV clinical trials along with the know-how to manage the complexities of your trial. Finally, here we explain why the right company must have the ability to understand you and your specific clinical trial needs while always putting patients first.

Over the past few days, we have discussed five important traits of Contract Research Organization (CRO) when it comes to your Cardiovascular (CV) clinical trials. Because we regard CV clinical trials one of our core strengths, we thought it beneficial to sponsors to see just how IMARC compares. Read on for a look at our background and some of our recent successes.

There is a new development in the story of Henrietta Lacks, the woman whose cancerous cells were obtained without her consent and developed into the immortal HeLa cell line.  You may recall that Henrietta presented to John Hopkins in Baltimore Maryland in 1951 and was treated for cervical cancer.  During her treatment, her doctors obtained a sample of healthy cervical cells along with a sample of the cancerous ones for testing.  Unexpectedly, Dr. George Otto Gey was able to keep the cells alive in a culture and they have been used without Henrietta’s permission in numerous research studies ever since.  In fact, you can still obtain a sample of HeLa cells today.  Unfortunately, Henrietta was never even informed of this and it wasn’t discovered until over 20 years later when Johns Hopkins contacted her children to see if they would be willing to give blood samples in order to better understand the immortal cells.  Not only has the Lacks family had no say in how Henrietta’s cells could be used, but they themselves have struggled to receive adequate medical care because the family has never been compensated in any way for their mother’s contribution to science.

In our last post, we revealed one of the most important aspects of choosing a Contract Research Organization (CRO) for your Cardiovascular (CV) clinical trial. But your research cannot end there. Several other elements will impact your trial, and you need to be well aware of them in order to successfully pass Food and Drug Administration (FDA) or other bureau inspections. Read on to find out how CRO employees and capabilities can affect your CV clinical trial and how to ensure best results.

Choosing the right Contract Research Organization (CRO) for your Cardiovascular (CV) clinical trial is imperative for so many reasons, but a strong foundation and a robust background are the building blocks for various other elements. If you are searching for a CRO for your upcoming CV Clinical trial, read on to find out how a company’s background can affect your trial.

The New York Times published an article that poses an important question to researchers- Do new medical procedures, products, and drugs work better than the old practices that they commonly replace?  It is a similar question that consumers are faced with every time a new version of their favorite cell phone is released- it is new, but is it necessarily better?

One of the fundamental principles of Clinical Research is: “if it is not documented, it is not done”. The attributes of source documentation, we, as research personnel, should be looking for are ALCOA: Attributable, Legible, Contemporaneous, Original and Accurate.  (The IMARC ALCOA Checklist is a helpful tool for understanding the importance of these qualities.)

For those involved in clinical research, whether it is at the site, sponsor, or CRO level, it can be easy to get caught up in the day to day rigor of collecting data; resolving action items all while juggling study staff schedules and fielding patient phone calls.  It is Grayson Clamp that reminds us why we as clinical researchers in the medical device industry do what we do.

In order for a new medical product to reach patients it must first be proven safe and effective and then be approved for use by the governing regulatory body. Clinical trials are the vehicle to bring these innovative technologies to patients and evaluate them in support of regulatory approval. Unless a product is approved under the appropriate regulations for a specific use, it cannot be commercialized for that indication. In clinical research the products are still investigational, and even in a hospital setting, these products are treated differently.

Often clinical research trials are conducted through large, academic medical centers. This is understandable as the cost of a research department infrastructure can be beyond the budget for a community hospital.  Yet for those community hospitals willing to become involved in clinical research trials, the dividends to the institution, its staff, and the community are phenomenal. A few of these benefits are reviewed.

Do you know why rules, regulations and standards exist? What exactly is Good Clinical Practice and how does this help protect patients and data integrity?

Dr. Robert Findling, Director of Johns Hopkins Division of Child and Adolescent Psychiatry and leading researcher in pediatric psychopharmacology, views being a principal investigator as “a privilege, not a right.” Dr. Findling has been noted as saying “with privilege comes great responsibility”.  Principal investigators who subscribe to this philosophy can set themselves apart by leading the development of cutting edge technology and novel treatments. According to 21 CFR 812.100, General Responsibilities of investigators, P.I.s are responsible for conducting research according to the federal regulations, agreements with the sponsor, the investigational plan, and the requirements set forth by the IRB.

I ran across an article in MDDI on virtual prototyping that could have an impact on clinical trials.  There is mixed opinion on the value of clinical trials.  Advocates claim they are necessary to ensure patient safety, while many in the device industry argue trials are only necessary for complex medical devices.

It’s an unfortunate reality in clinical research; oftentimes sites struggle to recruit subjects.  Frustration trickles down from the principle investigator and on down to the coordinators as sponsors put pressure on sites to enroll, enroll, enroll.  What are the barriers to recruitment and how can they be overcome?

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?

Running a clinical trial is a tremendous effort, requiring extensive resources.  No company wants to spend any more effort than required to get their product to market.  A recent whitepaper published by ImageIQ talks discusses the application of preclinical study in clinical trials to help save time and money.

In order for a new medical product to reach patients it must first be proven safe and effective and then be approved for use by the governing regulatory body. Clinical trials are the vehicle to bring these innovative technologies to patients and evaluate them in support of regulatory approval. Unless a product is approved under the appropriate regulations for a specific use, it cannot be commercialized for that indication. In clinical research the products are still investigational, and even in a hospital setting, these products are treated differently.

Being a CRO that specializes in helping companies gain FDA and world-wide approval through monitoring, auditing, training and consulting services- it’s fair to say we’ve come across a wide range of fellow CROs, investigative sites, research teams, and hospital systems. It’s amazing how much innovation exists- not just with the investigative products- but with technological advances to platforms used the healthcare industry.

The Entrepreneurs-in-Residence Program (EIR), a program at the Center for Devices and Radiological Health (CDRH), brings entrepreneurs, innovators, and government employees to combine the principles of lean engineering in rapidly testing, validating and scaling new approaches to the development in areas that impact innovation with the goal of delivering transformational change. This change, specifically in the medical device arena of public heath, would provide patients in the U.S. to high-quality, safe, and effective devices quicker.

Informed consent is arguably the most important aspect of patient protection in clinical research. The informed consent process is intended to protect the rights and welfare of subjects by educating them about their potential participation in a clinical trial. Unfortunately, informed consent remains an issue today. In fact, the FDA has sent out many warning letters regarding informed consent over the last few years.

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?

A project that has long been in the mind of Sandra Maddock’s has come to life.  The challenge was how to translate key events in clinical history into a series of images that depicted both the amazing and tragic events that have impacted medical research.

Clinical trials are a crucial step in the process for new products to reach patients. The information and data those trials yield provide FDA with the evidence to decide whether a product is both safe and effective for the public. But what happens if that crucial information is missing? By only looking at pieces and parts, it’s hard to see the full picture. With out knowing the whole story, could a vital piece of the puzzle be missing? Could missing data put patients at risk?

You did it!

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.

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 order for a new medical product to reach patients it must first be proven safe and effective and then be approved for use by the governing regulatory body. Clinical trials are the vehicle to bring these innovative technologies to patients and evaluate them in support of regulatory approval. Unless a product is approved under the appropriate regulations for a specific use, it cannot be commercialized for that indication. In clinical research the products are still investigational, and even in a hospital setting, these products are treated differently.

Minority participation in clinical trials continues to be a concern for industry professionals.  As stated in a blog posted on diversity in clinical trials, Dr. Kwame Osei says “minority participation in clinical trials remains lower than in the general population, with minorities making up only 10% of participants in multicenter clinical trials.”  Not only are minority participants lacking, but minority researchers are lacking as well.  The resulting danger of this reality lies in the tremendous amount of data that remains unknown, yet could have a substantial impact on clinical research.

Half the battle when facing obstacles or challenges is proper preparation. Knowing what types of challenges you may face is one way to ensure you have a well-thought out plan for the situation. So much opportunity exists around the world and as of late it has been an industry trend to operate studies outside the US.

Recent widespread recalls of investigational products have led to harsher scrutiny and stricter rules from the Food and Drug Administration (FDA). Steps take to prepare for trials in the past are no longer enough. The path to FDA approval requires tremendous organizational skills and attention to detail to navigate; but with the right preparation and commitment to compliance, all of these challenges can be overcome.

Not too long ago we posted a blog on cell therapy trials. This is an emerging field in clinical research and one we are very excited about. While the FDA is still in the process of building a foundation of the cell therapy industry, there exists a need for this type of medical development to meet the needs of patients. Before any of these life-saving innovations can reach the public, they must meet the requirements for being proven safe and effective in clinical research- and have success in clinical trials. Looks like FDA is taking steps in this direction.

As part of the Patient Protection and Affordable Act, the Sunshine Act requires medical device, pharmaceutical and similar companies to report any payment or other transfer of value to the Health and Human Services (HHS). This will effect many companies that conduct clinical research and clinical trials, but the question remains- will this negatively impact physician’s willingness to participate in research?

In clinical research having a well-run, compliant study is a top priority. Ensuring patients are protected and resulting data has integrity, it’s important to be experts in all aspects of your study. If your trial involves imaging, understanding how to get the most out of your data is not only smart- it’s cost effective. From a recent article published on GEN - Genetic Engineering & Biotechnology news, here are nine tips to help bring products to market faster with these ways of optimizing preclinical imaging: