Medical Device CRO Blog

Inept Clinical Trial Endpoints Can Cost Billions

John Lehmann — Fri, 09 Nov 2012 13:10:00 GMT

Here’s a staggering statistic for you- inefficient clinical trials are costing some companies between $4 and $6 billion each year in unnecessary expenses. This is according to study data published by the Tufts Center for the Study of Drug Development (CSDD).

This report was also covered by an article on RAPS which points to the fact that the problem is widespread. However, in clinical trials the major issue lies in unnecessary endpoints and the expenses associated with collecting data to meet these endpoints. Trial endpoints can be crucial as they can be defined as “results, conditions, or events associated with individual study patients that are use to assess study treatments.” Nevertheless, something seems to be amiss if this becomes a wasteful aspect of the research process.

Other interesting finds noted in the report include:

An average 22.3% of all clinical trial procedures are considered to be non-core, including 17.7% of Phase II procedures and 24.7% of Phase III procedures.
Half of all procedures and 54.3% of Phase II procedures and 47.9% of Phase III support primary and key secondary endpoints.
The typical clinical trial protocol has an average of 13 endpoints, with the number of less essential endpoints per protocol nearly doubling the average level observed 10 years ago.

While this data is resulting from a study of drug development costs, it sheds an interesting light on the idea of extraneous endpoints in clinical trials. If a study is not stream-lined with a well-written and well-defined protocol, the study is doomed from the start. Endpoints in a clinical trial can be a challenging and critical study design decision. For more information on this aspect of a trial check out this useful presentation.

Why do you think the trend is for a wasteful increase in endpoints? Is there such a thing as too much information?

Photo Credit: 401(K) 2012

Medical Device Industry Impacted by Hurricane Sandy

Brandy Chittester — Thu, 08 Nov 2012 13:02:00 GMT

Seeing those greatly effected by the recent storms is devastating. While in various places the assessment of damage is still being assessed, physically, FDA also is assessing the set-backs from the recent natural disaster. This was expressed in a recent FDA Voice Blog by Margaret Hamburg, M.D., FDA Commissioner.

The Commissioner notes that while many of us think of these major disasters in terms of property damage, FDA has a wider field of view. “At FDA we also have to focus on the effects of natural disasters on the safety of the products we regulate and that consumers and patients depend on – everything from fresh produce to canned foods to medicines and high-tech medical devices.”

While the blog points out that FDA prepares early for any type of possible disaster, even with great preparation obstacles can occur. In fact, another recent article by RAPS, notes that many industry related functions are feeling the effects of Hurricane Sandy, including:

The Office of Personnel Management (OPM), the federal office charged with closing and opening government facilities, shut down FDA for two days as the storm bore down on the region
The closure of its offices for two days would not be without consequence for sponsors with target dates around those two days

This disruption will be felt more by those who submitted documents via paper submission in contrast to those who submitted to FDA electronically. Overall this could mean a costly delay for some sponsors.

However, it’s important to remember that FDA, industry, and public’s top priority in the realm of clinical research, medicine and innovative devices are the people who at the other end of these life-saving products. So, whether FDA ensures patient safety through the rigorous review of submissions- or by FDA inspecting facilities impacted by the storms, keeping people save remains the #1 goal.

Check out the FDA Voice Blog and share your thoughts on FDA’s preparation and response during this time.

Photo Credit: NASA Goddard Photo and Video

IRB Reporting Compliance - Whose Job is it?

Sandra Maddock — Wed, 07 Nov 2012 13:25:00 GMT

Recently, when discussing Institutional Review Board (IRB) adverse event reporting, a Project Manager for a leading medical device Contract Research Organization (CRO) brought up a valuable question regarding reporting compliance- whose job is it to ensure an investigator is compliant with IRB reporting policies?

According to ICH GCP E6 5.1.1, the sponsor is responsible for implementing and maintaining quality assurance and quality control systems to ensure that trials are conducted and reported in compliance with the protocol, Good Clinical Practice (GCP) and the applicable regulatory requirements.

The sponsor may transfer any or all of the sponsor’s trial-related duties and functions to a CRO, but is ultimately responsible for the quality and integrity of the data. The CRO should implement quality assurance and quality control (ICH GCP E6 5.2.1).

In 21 CFR 812.46, it is the sponsor’s responsibility to secure compliance when it is noted that a investigator is not complying with the signed agreement, investigational plan, or any conditions of approval imposed by the reviewing IRB.

IMARC Research, Inc. uses the FAIR Shake technique as the CRO delegated by the sponsor to ensure that the research site is in compliance with:

Federal Regulations
Agreements with the sponsor
Investigational Plan
Requirements of the IRB

IMARC monitors review a site’s IRB adverse event and non-compliance reporting policies and work with the site to ensure IRB reporting compliance.

Whose job do you think it is to make sure that the site is following its IRB’s policies? The sponsor? The CRO? The PI? The coordinator? The IRB? Explain your thoughts below.

Photo Credit: jetheriot

Did You Miss it?

John Lehmann — Tue, 06 Nov 2012 13:17:00 GMT

We continue to reach out to our colleagues, customers, and friends in the most convenient places- from Facebook to Linked-In to Twitter, and even in your very own inbox! Today we distributed the 21st issue of the IMARC e-Newsletter.

We pride ourselves on proactively providing information devoted to various areas of clinical research, making it easier for you to navigate through the regulations, understand the current industry climate, and stay on the cutting edge of industry news.

Our e-Newsletters include various areas of focus:

Featured Articles
Industry Hot Topics
Upcoming Speaking Engagements
News Briefs
IMARC Staff Bios

We issue a new edition every 6-8 weeks full so don’t miss out on our next edition! Sign-up now to receive your free issue: Subscribe here!

Photo Credit: IMARC Pet Photos!

Top 10: Cleveland Clinic Medical Innovations

John Lehmann — Mon, 05 Nov 2012 13:28:00 GMT

The wind, rain, and power outages of Hurricane Sandy did not stop the 2012 Medical Innovation Summit that welcomes approximately 1,000 leaders in new medical technology to convene at The Clinical Clinic. The Summit, held over 3 days in North East Ohio, is attended by investors, regulatory, clinical, medical affair and business development executives in the healthcare industry, buy and sell-side researchers and other healthcare service providers.

One of the highlights of the Summit is the Cleveland Clinic’s list of the “Top 10” Medical Innovations for 2013. Dr. James Merlino, Chief Patient Experience Officer and Dr. Michael Roizen, Chief Wellness Officer, both of the Cleveland Clinic, presented the list of breakthrough technologies that were selected from 150 nominations from 110 Clinic experts.

As noted in the Cleveland Plain Dealer, here are the Top Ten innovations:

Bariatric surgery for diabetes control
Neuromodulation therapy for cluster and migraine headaches
Mass spectrometry for bacterial identification
Novel medications for advanced prostate cancer
Handheld optical scan for melanoma
Femtosecond laser cataract surgery
Ex-Vivo Lung Perfusion system
Modular devices for treating complex aneurysms
Breast tomosynthesis
Medicare Better Health Rewards Act

IMARC Research, as a medical device CRO, is excited to see -“Modular Devices for treating complex aneurysms” as the 8th most innovative technology. New technology using grafts and stents allows physicians to treat potentially deadly aneurysms with minimal invasive endovascular repair. The use of different types of modular devices translates to a better experience to the patient. The risk and time of the procedure is decreased as well as the amount of time spent in the hospital post procedure.

Other innovation winners include medications for prostate cancer, laser cataract surgery and therapies for migraine headaches. What types of new technologies would you like to see healthcare experts develop in the future?

Photo Credit: sam_churchill

The Cost-Saving Power of Study Evidence

John Lehmann — Fri, 02 Nov 2012 11:22:00 GMT

There has been a downward trend in certain knee procedures for osteoarthritis. According to a recent study published , researchers from Emory University examined the trend in hopes of showing the effectiveness of study evidence and the positive impact it can have on study dollars. This is because the New England Journal of Medicine published many reports between 2002 and 2008 associated with changes in clinical practice patterns.

The study seemed to have an impact on practice patterns, researchers examined ambulatory surgery data from Florida and found that the number of arthroscopic debridement and lavage procedures per 100,000 adults declined by 47 percent between 2001 and 2010. During that period, the New England Journal of Medicine published results from two randomized controlled trials that found no benefit from arthroscopic debridement and lavage procedures. This had a financial impact, as these procedures declined from approximately $83-$138 million annually over this ten-year period.

It seems many patients opted for physical therapy over surgery. This again had a saving impact, as it is calculated that national savings were $39.2 million - $94.3 annually.

The challenge is that physicians in our fee-for-service system have little incentive to abandon these surgeries. The only way a study like this can have a lasting impact is if:

Physicians have a willingness to abandon unnecessary surgeries
Patients are willing to take on a new thought process on these types of surgeries
Better public education to understand the standard of practice and treatment procedures

This study shows that trials and comparative studies that examine widely used therapies with questionable value can have help reduce potential cost. What are your thoughts on this study? Do you think it can have a lasting impact on unnecessary procedures? Share your thoughts below.

Photo Credit: 401(K) 2012

GCP… What Does it Mean?

Brandy Smith — Thu, 01 Nov 2012 11:23:00 GMT

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?

Protecting patients is at the core of clinical research and one of the ways research teams can ensure human subjects are protected is through holding up rules, regulations and standards set forth. Good clinical practice (GCP) is something that encompasses all these things because it is:

An attitude of credible excellence in research that provides a standard for clinical study design, implementation, conduct and analysis

Many cornerstone events have occurred in history to make clinical research what it is today. Often times the biggest events in patient protection had roots in some of the most unethical tragedy. We have a whitepaper devoted to the key principles that make up good clinical practice, and how to take “good to great” in clinical research.

Since this topic is so important we’ve created a one page guide you can print for free which defines GCP, describes what makes up GCP, and ultimately reminds us that the responsibility for clinical research ethics rests on all of our shoulders.

Use our infographic as a memento- the only way to practice clinical research is with Good Clinical Practice!

Should THIS be the Next Global Priority?

John Lehmann — Tue, 30 Oct 2012 13:18:00 GMT

Recently an article was published in PLOS titled “Strengthening Medical Product Regulation in Low- and Middle-Income Countries” which strongly suggests developing countries must become a global health priority. In fact, The Word Health Organization (WHO) recognizes regulatory system functions as one of the six core building blocks of health systems.

There exists an essential value of medical product regulatory systems in regulatory domains such as:

global product supply chains
clinical trials
premarket approval
post-market surveillance
regulatory science

Despite this fact, many emerging countries have little attention focused on this important building block. The article points out that “few global initiatives focus on strengthening low- and middle-income country medical product regulatory systems.” Should this become a global priority? As stated in the article:

Globalization and the scaling up of medicines and vaccines to the developing world are highlighting the urgent need for systems to assure product efficacy, safety, and quality.

It’s important to note that this request comes with challenges. As noted, “There are numerous competing priorities for political and financial support, especially in the wake of the global financial crisis” but the need for increased regulatory function must remain as a growing priority.

Check out the article which is full of valuable points, case studies, and references on this topic. Do you think these low- to middle-income countries need to provide incentives and more sustainable economic development before this can become a global priority?

Let us know your thoughts.

Photo Credit: Judy **

Conducting a Well-Controlled Clinical Study When Clinical Data is Required

Sandra Maddock — Mon, 29 Oct 2012 11:50:00 GMT

There continues to be much discussion over the FDA’s 510(k) program, which has led to controversy and confusion over the direction of the program. In fact, we have posted many blogs devoted to this topic, so we thought it was time to create a whitepaper focusing on the topic.

The purpose of the whitepaper is to establish the current status of the 510(k) process with regard to clinical data requirements, and then to begin to define some considerations that should be given to conducting a well-controlled clinical study, if, indeed, clinical data is required.

We realize that running a clinical study could be a monstrous undertaking for a company who historically has not had to produce clinical data for their 510(k) submissions, and this white paper has only begun to touch the surface.

Take time to download and review the whitepaper, we hope it helps provide you with a plan if your 510(k) requires clinical data.

Please let us know what you think.

Photo Credit: University of Denver

Affordable Care Act: Impacting America’s Leadership?

John Lehmann — Fri, 26 Oct 2012 11:30:00 GMT

Affordable Care Act: Impacting America’s Leadership? At the Medical Device Conference 2012 (MedCon), held at Xavier University, in Cincinnati, Ohio, Kem Hawkins, President and CEO of Cook Incorporated and Cook Medical, delivered a powerful keynote address. In his speech, Hawkins proposed that FDA has not demonstrated the leadership necessary for the United States to maintain its position as global forerunner in the healthcare arena. Hawkins also touched on his opposition to the medical device tax included in the Patient Protection and Affordable Care Act (ACA).

Prior to the MedCon, Hawkins suggested that the claims of the ACA may be inaccurate, as the tax has already impacted U.S. healthcare leadership and medical innovation. In an article published in MedCity News titled “ACA’s 2013 medical device tax has already killed jobs, expansion plans”, Hawkins refutes the claim that proposed tax will have little effect on medical innovation. In fact, this tax on top of existing taxes and regulatory systems will drive research, development and manufacturing out of the United States. In attempts to counterbalance the 2.3 % tax on medical device sales, companies have started to take the following actions:

Limit research budgets, decreasing the availability of new medical treatments to patients
Consider clinical research studies and development of next-generation products outside of the U.S. to growing markets like China, India and South American countries
Limit capital investment in new factories or expanded existing plants in the U.S.
Lay-off workers or outsource jobs outside the U.S.

Hawkins argues against the new tax for the negative impact it may have against U.S. patients having access to breakthrough technology. The tax may also threaten U.S. and FDA’s position as a global leader in medical device research and innovation.

Does the new tax grow or limit the global leadership role in healthcare? Are there any ways that the Act can positively effect jobs in the U.S? What are potential strategies that medical device companies can develop in the U.S. to grow leadership and innovation? Share your opinions below!

Photo Credit: PMillera4

Change Your Focus from Device Compliance to Device Quality

John Lehmann — Thu, 25 Oct 2012 12:23:00 GMT

In a recent speech in Minneapolis, Steve Silverman Director of the FDA’s Center for Devices and Radiological Health’s Office of Compliance, urged the industry to expand their focus beyond compliance and build high-quality medical devices. The speech in was based on the agency’s focus on building a quality framework. Silverman explained that while the FDA will continue to enforce regulation, its success won’t be judged by that enforcement work alone.

In an article in MedCity News, Silverman indicated that compliance with the regulatory framework is a baseline, but high-quality devices are in the best interest of patients. Historically the FDA has been focused on compliance. The challenge is that the FDA only inspects a fraction of the firms that fall under its jurisdiction globally. Silverman indicated that 66% of firms are not regulated and 95% of firms are not inspected globally, which is a staggering number.

It’s been an ongoing mission of FDA to provide data transparency so people can easily access the variety of data including:

Adverse event reports
Inspection data
Recall information among

Silverman also noted it’s important to release information in a highly organized and consistent manner so that patients can compare medical devices and make informed decisions about possible treatments. “There is significant risk in doing this and so we have to provide context,” Silverman said. “It’s not the position of the agency to be a Consumer Reports. We don’t want to put out a score.”

The goal is to build a collaborative environment among all groups. What are your thoughts on this topic? Do you feel it’s important for the FDA to expand their focus beyond compliance? Or are they getting involved in areas where they do not belong.

Share your thoughts below.

Photo Credit: Cayusa

Understanding on the Benefits of the FAIR Shake™ Training Method

Brandy Smith — Wed, 24 Oct 2012 11:30:00 GMT

We recognize that it might not be easy to quickly grasp the concept behind the FAIR Shake™ training program, so we have posted a video on our company website that we believe will give you a better understanding of the training program. Sandra Maddock, CEO and President of IMARC, is featured in the video and walks you through the training methodology.

The FAIR Shake™ technique takes an otherwise complicated maze of requirements and breaks them down into four simple areas that can be applied to clinical research questions.

The goal of The FAIR Shake™ program is to foster a pattern of thinking that will allow you to navigate through the complexity of the regulatory framework in a very simple way that is based in regulatory fact as opposed to popular opinion. This technique will position you to raise the bar on your own study teams as you gain confidence in your ability to wage an educated debate when potential areas of non-compliance are raised.

You can also access the video on IMARC’s YouTube channel or download the FAIR Shake™ whitepaper for a more in-depth overview.

When was the last time you gave your study a FAIR Shake™?

New FDA Program: What Does This Mean for 510(k) Submissions?

John Lehmann — Tue, 23 Oct 2012 11:30:00 GMT

In an effort to promote innovation while protecting the population at large, FDA has been on a path to revise the existing regulatory pathway surrounding the 510(k) process for medical devices for several years. This continues to be an area of many questions and considerations. In fact, we’ve devoted a whitepaper to these issues to help researchers understand the 510(k). Recently FDA released a Draft Guidance on the eCopy Program for Medical Device Submissions. While this system is currently voluntary, the draft guidance gives industry an idea of what might be in store for device submissions.

The draft guidance describes eCopy as “an exact duplicate of the paper submission, created and submitted on a compact disc (CD), digital video disc (DVD), or in another electronic media format that FDA has agreed to accept, accompanied by a copy of the signed cover letter and the complete original paper submission.”

As noted in a recent news-release on Regulatory Focus, the guidance lists explicit details about:

How to submit an eCopy
Steps to assure that a submission is up to FDA standards
How to submit to different FDA centers
Common mistakes made in submissions and
How to avoid the common mistakes made in submissions

How will this effect the device submission process and 510(k)? According to another recent guidance released by FDA, “Most 510(k) submissions will be subject to a user fee as described in the guidance and all 510(k)s will be subject to the requirement for an eCopy. Submitters should note that 510(k) submissions will not be processed and distributed to the appropriate Division for review without confirmation of user fee payment and a validated eCopy.”

It plainly states in the “Actions on Premarket Notification 510(k) Submissions: Effect on FDA Review Clock and Goals” Guidance, 510(k)s need a valid eCopy in order to initiate review.

Do you think this is just an administrative hurdle to add to the 510(k) submission process? Or, do you think this will help streamline reviews? Voice your opinion below.

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New Industry Trend? Warn Wall Street Before Receiving FDA Warning Letter

John Lehmann — Mon, 22 Oct 2012 11:00:00 GMT

It hit the headlines in a dizzy twist on words. The CEO of St. Jude put the cart before the horse in warning investors that he was expecting a warning letter from FDA before one was actually even issued! According to a report on MedCity News, this type of announcement apparently has no precedent. Have you ever heard of a company proactively telling Wall Street they’re going to receive the dreaded warning letter before receiving it- or even a FDA form 483? This was something that was on the mind of analyst Bob Hopkins of Bank of America.

So, what does this mean for our industry moving forward? Is this going to be the new trend- beating FDA to the punch? The CEO of St. Jude, Dan Starks, made comments on how investors don’t like surprises, and urged people to be realistic about the role of warning letters in today’s regulatory arena.

In fact, Starks stated, “Another reason we made the comment is that in the long run, we think it’s good for our markets if the public knows that the FDA is exercising its regulatory oversight of medical device companies in a very rigorous and robust way, and it’s clear to us that FDA is doing that.”

Questions that analyst Hopkins mentions in the article are valid inquiries:

Did the FDA uncover something and told you about it?
Have you uncovered something- and wanting to be proactive- notify FDA?
Why did you make that comment?

There are a lot of curiosities and questions left to be answered. Hopefully FDA will release information soon so the public is aware of the details. After all, the letter hasn’t even been issued yet, as Stark stated, “It’s a risk, and don’t be shocked if that risk is realized.” Reuters also covered the story with the same tone of unanswered questions.

How will this play out on Wall Street? Was this a smart move? Can we expect to see more warning letters and 483’s handled this way? What are your thoughts?

Photo Credit: Mathew Knott

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NEW!! FDA Guidance for Review/Approval Time-Lines

Brandy Smith — Fri, 19 Oct 2012 12:10:00 GMT

Stemming from the much anticipated Medical Device User Fee & Modernization Act (MDUFMA), FDA issued a new guidance regarding Premarket Approval Applications (PMAs) review and approval timelines. As the guidance plainly states in the introduction “the additional funds obtained from user fees will enable FDA, with the cooperation of industry, to improve the device review process to meet certain performance goals and implement improvements for the medical device review process.”

As part of the improvements to the medical device review process, the new user fees set decision goals as follows:

180 Days: Original PMAs and Panel-track Supplements without panel
320 Days: Original PMAs and Panel-track Supplements with panel
90 Days: Real-time Supplements
180 Days: 180-day Supplements
A shared goal for total time from application submission to decision
"Missed MDUFA Decision" notices for companies whose reviews have missed goals by 20 days

FDA also lays out in the guidance specifics on when the review “time clock” starts and stops with each step regarding FDA’s actions:

Approval Order
Approvable Letter
Major Deficiency Letter
Not Approvable Letter
Denial Order
Acknowledgement of Voluntary Withdrawal

As with any newly established goals, these are ones FDA hopes will be easier to obtain as processes improve. In fact, the agency hopes to reach the timeline goals 90%-95% of the time- consistently- within the next five years.

Hopes are that this guidance will help all players involved, specifically Center for Devices & Radiological Health (CDRH) and the medical device industry, with satisfaction in review times and goals. After all, with a drastic increase in User Fees for PMAs, hopefully industry gets what it’s paying for.

Have you read the new guidance? Do you think this is a positive outcome from the new MDUFMA agreements? Share your thoughts below.

Photo Credit: Moonrhino

Are Implantable Devices On Their Way Out?

John Lehmann — Thu, 18 Oct 2012 11:40:00 GMT

A PricewaterhouseCoopers report titled “Operating performance in the med-tech industry: Trends and imperative” was recently published with highlights the operating performance trends for the medical device industry and its various segments. Being a medical device CRO, we read with interest the report, and an article in MassDevice which also covered the report.

Interestingly enough, the report calls out the decline in operating performance of implantable devices indicating that "the implantable devices segment has been the most consistent top operating performer relative to other segments, driven by significantly higher gross margins," according to PwC. "This advantage is declining, however, likely due to the maturation of the cardiology and orthopedic implant markets (both of which have been characterized by low growth and reimbursement challenges) and changes in purchasing dynamics and buyer behavior."

To underscore the report, more than 40% of companies in the implantable device segment saw an operating decline and only 1 in 4 saw improvement. Conversely, the PwC report indicates that nearly 1/3 of IVD companies’ increased operating performance during that same time (2005-2007).

The report hopes to not only explain how various med-tech segments are doing, but also provide direction for med-tech companies as to “which levers to pull to improve their operating performance” according to their website. In brief, here are the recommendations to help improve medical device companies:

Broaden innovation
Move up the productivity curve
Transform the go-to market model
Revitalize growth strategies

While implantable devices have long been considered the top performer for many med-tech companies, this may be the start of a new “King” in the medical device market. In fact, there seems to be an upward trend concerning in vitro diagnostics (IVD) and has become the leading growth segment.

Do you think these trends can turnaround? Or is this is start of the end for implantable devices? We want to hear from you.

Photo Credit: llamnudds

IRB… As Easy as 123!

John Lehmann — Wed, 17 Oct 2012 11:00:00 GMT

The key players in a clinical investigation are infamously made up of Sponsors, monitors, investigative sites, and patients. A fundamental part of the team is also the Institutional Review Board (IRB), as they oversee the conduct of clinical research. Per the FDA’s IRB information sheet, “IRBs are responsible for continuing review of ongoing research to ensure that the rights and welfare of human subjects are protected.” That’s a tall order!

To help all the key players in an investigation better understand the role and responsibilities of an IRB, we’ve put together an infographic cheat-sheet called:

IRB’s 123’s

FDA has placed an enormous responsibility on institutional review boards. The rules that govern IRBs are clearly laid out in 21 CFR 56, which contains general standards for IRB:

Composition
Operation
Responsibility

Check out the infographic and feel free to print our guide as a tool for your entire research team! After all - no matter what position you play on the clinical research team, we’re all responsible for protecting the rights and welfare of human subjects.

Let us know what you think! Any ideas for other tools? Comment below.

Where is EMA Falling Short? See Audit Results!

Sandra Maddock — Tue, 16 Oct 2012 11:52:00 GMT

Conflict of interest can be defined as occurring when an individual or organization is involved in multiple interests, one of which could possibly corrupt the motivation for an act in the other. While many may see disclosure of conflict of interest as just another form to check off the list, it’s an important aspect in a study to ensure the trial is conducted with the utmost integrity and responsibility.

Per the regulations, most clinical trials require disclosure of conflict of interest (COI). This is required by the investigator(s) to the sponsor, then from the sponsor to the FDA. The FDA then considers whether adequate steps are taken in the design, conduct, reporting and analysis of studies to minimize bias. However; the idea of conflict of interest should extend further then just in clinical trials. What about if there is a conflict of interest between those reviewing research? What happens if there was an unseen influence on their decision?

It seems this is something EMA is falling short to adequately address. According to recent reports, auditors have discovered that EMA “despite its attempts to increase transparency and implement conflict-of-interest (COI) policies, is falling short of its responsibilities to, adequately manage COI situations. This audit was performed by the European Court of Auditors (ECA) and had a few recommendations for the agency, including:

Screening candidates for conflict of interest before their appointment;
Establishing conflict of interest policies and procedures which would ensure that conflict of interest situations are managed to a comparable standard by national authorities performing outsourced tasks;

It wasn’t too long ago that FDA released a guidance called, “Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: Public Availability of Advisory Committee Members' Financial Interest Information and Waivers.” This guidance also touched on 21 CFR 54; Financial disclosure, which can be a source of bias for the outcome of a study. While the guidance released is specific to advisory committees, its goal is to help provide clarity to the FDA processes, and standardize of public disclosure of the COI information.

Do you think EMA could benefit from more transparency like the FDA? Do you agree with the recommendations? Let us know what you think.

Photo Credit: Tax Credits

How Do We Regain Society’s Confidence in Clinical Trials?

John Lehmann — Mon, 15 Oct 2012 11:29:00 GMT

We live in a fast-paced world; a world where new technology and innovation develops in rapid succession. We are always seeking the “latest and greatest” in technology. Intertwined in this world of technology and innovation, lies the world of clinical research. People who are ill or disease-ridden have faith and hope that a miracle cure or life saving device is just around the corner. But what happens when society as a whole loses faith in clinical research? Who will volunteer for research studies when trust in the system fails?

Researchers know that at the basis of clinical research lies the inherent burden to protect the rights, safety and welfare of all subjects who have agreed to participation. It is imperative that subject’s have some degree of confidence that their rights, safety and welfare are at the fore front of any clinical research study. In order to keep public trust in the safety and efficacy of clinical trials, stricter policies on clinical oversight are warranted.

Often times, the public is made aware of only the negative effects of research. It is often years before the positive results of such trials are brought into the public eye by mass media. However, the truth is, almost all life-saving drugs and devices are available to people today because of clinical trials.

In an article published in American Society of Clinical Oncology, the following elements were listed as essential to ensure public trust in clinical trials:

Ensure safety precautions for clinical trial participants and their fully informed consent
Ensure the validity and integrity of scientific research
Enhance the educational training of clinical scientist and research staff to maximize standards of research conduct
Promote accountability among all those involved in clinical research
Promote professional and public understanding of clinical research

Through a well-developed plan to promote and educate society regarding clinical research and to ensure that all clinical trials are conducted with the utmost integrity, we can once again allow the public to have confidence and an eagerness to be part of ground breaking science. In order for this to occur, researchers must guarantee that they are placing the rights, safety and welfare of their subjects above all other aspects of the clinical trial.

Have you experienced a decline in the amount of subjects who participate in clinical research? How can we regain the public’s trust in clinical trials? Share your thoughts below.

Photo Credit: EU Social

Protocol “Waiver” from the Sponsor- Is That Enough?

Brandy Smith — Fri, 12 Oct 2012 12:09:00 GMT

At times, a Sponsor may provide a site with a memo allowing the site to enroll a patient who does not meet all inclusion or exclusion criteria. Or a Sponsor may give the site pre-approval to deviate from the protocol-defined visit windows. Is this waiver enough? Would the investigative site be covered in the event of a federal audit?

What is in the Regulations?

812.150 (a) (4): Deviations from the investigational plan

Prior approval by the sponsor is required for changes in or deviations from a plan, and if these changes or deviations may affect the scientific soundness of the plan or the rights of the subjects, IRB approval is also required

812.35 (a) (1): changes in the investigational plan requiring prior approval

A sponsor must obtain IRB approval prior to implementing a change to the investigational plan

312.66: Assurance of IRB review

The investigator shall assure that he or she will promptly report to the IRB all changes in the research activity and that he or she will not make any changes in the research without IRB approval, except where necessary to eliminate apparent immediate hazards to human subjects.

In addition to the regulations, the Biomedical Monitoring (BIMO) checklist states the following:

Verify the Investigator followed the study protocol approved by the IRB
Limited prospective exceptions to the protocol (e.g. agreement between the Sponsor and Investigator to enroll a single subject who does not meet all inclusion/exclusion criteria), like protocol amendments must be reviewed and approved by the IRB prior to implementation.

A review of FDA warning letters indicated investigative sites and Sponsors are being cited by the FDA for failure to obtain IRB approval prior to implementing approved protocol waivers. Various citations are listed below:

Although you received a letter from the Sponsor’s representative that permitted you to conduct testing outside of the protocol, you never sought or received IRB approval to deviate from the protocol.
The protocol included a provision that selection criteria maybe waived by the Sponsor-Investigator if approved by the IRB on a case-by-case basis. You failed to obtain advanced IRB approval.
You received an email from the Sponsor stating it is “ok to ship samples on the next day following collection.” You did not, however, seek or obtain approval from the IRB for that protocol deviation.

It is easy to think that if the Sponsor allowed a waiver or deviation, then that’s enough. Studies move quickly and enrollment is so important – no one wants to miss out on enrolling a potential subject. However, it’s important to ensure all regulations are followed when conducting clinical research – whether you’re the sponsor or the site.

We know this is a hot topic in clinical research. Please share your experiences with us.

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510(k) RTA - Did FDA Shoot and Miss?

John Lehmann — Thu, 11 Oct 2012 12:13:00 GMT

It wasn’t too long ago that new recommendations for improving the 510(k) medical device review processes were published with the goal of installing a pre-review assessment that would check applications and reject submissions dibbed incomplete. FDA took steps forward with this plan and released the FDA Draft Guidance: Refuse to Accept Policy for 510(k)s (RTA).

FDA’s goal with RTA is to help streamline the review process, and hopefully grant faster approvals. The applications submitted would be pre-reviewed for based administrative completeness including criteria:

Submission contains table of contents
All pages of the submission are numbered
Inclusion of engineering drawings
Identification of predicate devices

However, recently industry has fired back claiming FDA’s guidance is not objective and could be more time consuming then the current review process. While FDA made it clear RTA is not meant to review the innovative products- rather just ensure completeness with submission- many feel that the checklists are too detailed and too subjective to really help both parties.

510(k) remains to be a hot topic across industry leaders. While it seems FDA is trying to make steps forward, others view them as steps in the wrong direction. To better understand the 510(k) process checkout the whitepaper, “510(k) Current Status & Considerations” and gain a better perspective on these types of submissions.

Have you had a chance to look at FDA’s draft guidance? Do you agree that this will become more burdensome then helpful?

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Why Use an Integrated EDC/EHR System in Clinical Research?

Sandra Maddock — Wed, 10 Oct 2012 11:00:00 GMT

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.

A recent article, “5 Reasons For Using Integrated EDC/EHR Platforms” explores the up and coming advancement of an integrated platform that could streamline processes within our industry. The article asks a pensive question, “Most researchers today are already using an electronic data collection (EDC) tool to help manage even early-stage clinical trials. Because the collection methodologies for electronic health records (EHRs) are similar, could a single system simultaneously be used for patient care in both the hospital/clinic and clinical trial settings?”

Many believe that using an integrated system will allow for better workflow in clinical research studies, and perhaps new tools in this area will help bring more innovative products to market in a quick, cost-effective method. How will this type of hybrid system prove beneficial? The article points to five reasons to consider using an integrated EDC/EHR product for a clinical research study:

Pre-identification of sites with appropriate patients for even the most tightly focused study
This, in turn, fosters fewer enrollment delays — an important consideration from not just a cost standpoint but from the implementation requirements of a competitive, go-to-market strategy.
Research costs are considerably lower due to certain economies
For example, study monitors and research associates do not need to travel to sites as often for source data verification because 80% to 90% of the data is typically taken directly from the EHR.
Greater pool of potential sites, even those that are research naive, because the startup requirements are significantly lowered through an integrated EDC/EHR platform
The potential patient pool is also increased, as those living far from large medical centers can now enroll through smaller, more localized clinics.
Improve data input accuracy
By removing the potential for transcription errors, data quality is improved.
Information that isn’t normally collected within a site’s EHR can be collected on eCRFs (electronic case report forms) that are displayed in the EHR interface.
Using one interface can help with problems in workflow and duplicate data entries.

Do you currently use a hybrid system? What are your thoughts on an integrated platform? Share your pro/con list below.

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Did You Miss the Risked-Based Monitoring Presentation?

Brandy Smith — Tue, 09 Oct 2012 11:59:00 GMT

In August 2011, FDA released a draft guidance document recommending a Risk-Based approach to monitoring. Risk- Based Monitoring combines the vigilance and data surveillance (key features of Electronic Data Capture systems) with traditional on-site data verification targeting critical data points. Rather than a standardized monitoring plan, Risk-Based Monitoring aims to adapt the monitoring plan to the changing needs of the Study, Site and Investigational Product.

With growing interest in Risked-Based Monitoring, President and CEO Sandra Maddock presented an audio conference on September 11, 2012 on Centralized vs. Onsite Monitoring – Applying FDA's Risk-based Approach. The presentation discussed the key principles of the current trends in research monitoring with a focus on the advantages of using a Risk Based Monitoring approach, while touching on topics like:

An overview of monitoring
Monitoring regulations and standards
Current Status of our industry
FDA’s draft guidance
Application using various case studies

Also available for review is the whitepaper “Centralized vs. Onsite Monitoring: A Sponsor’s Balancing Act” which acts as a guide to understanding the various aspects of what a monitor does on site, how this affects monitoring, and assessing the risk for onsite and centralized monitoring for a clinical trial.

IMARC Research is committed to being an industry thought leader on a wide-range of clinical research topics. We give periodic presentations throughout the year and welcome you to look through past presentations. If you have any thoughts regarding this presentation, or ideas on a relevant topic for a new one, feel free to share below!

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How Medical Device Development Is Different

John Lehmann — Mon, 08 Oct 2012 12:52:00 GMT

Each sector of the research industry faces its own unique challenges. For instance, take clinical research involving drugs versus devices. While some aspects of the research process and clinical trial are the same, their differences require special attention to have a compliant and well-controlled study. Likewise, an article titled, “Combating the challenges of medical device development,” investigates how medical device development is similar to other product development- but still faces unique challenges.

The article lists the following challenges that are specific to the medical device industry:

Strict regulatory regimes that demand proof of compliance and vary between markets
Potentially significant damage if you fall foul of regulatory bodies
Need to show traceability from user needs right through to delivered products
Need to have systems in place to ensure customer requests/complaints are managed and, if necessary, changes made to products
Everything needs to be documented and reported

The amount of regulation that is involved in device development definitely sets the industry apart. On top of this list, pile on another set of complications, including:

Increased competition
Need to sell into global markets
Need to shorten development time and time to market

It’s obvious the pathway to approval isn’t exactly broad and easy. Then again, the patients on the other end of approval deserve something that is proven safe and effective. While they may seem like burdens or obstacles these challenges ultimately help the people who will receive them.

What are your thoughts on device development? Can you think of any other unique challenges to add to the list? Let us know below.

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Do Medical Devices Need an FDA Security Plan?

John Lehmann — Fri, 05 Oct 2012 11:36:00 GMT

One great aspect of the research industry is being on the cutting-edge of new, innovative technologies. Looking back at the history of medical devices, it’s amazing how far technology has brought us. New devices are incorporating more complex technologies then ever before. These medical advances are to help treat patients; however, does the increase in innovation also mean an increase in safety risks?

This is something the US Government Accountability Office (GAO) is taking into consideration. In fact, in a recent report, “FDA Should Expand Its Consideration of Information Security for Certain Types of Devices,” GAO outlines the safety concerns of certain advanced devices as well as the recommendations to best protect patients.

One of the biggest concerns outlined in the report concerns the threats, vulnerabilities, and security risks associated with implantable devices. GAO voices that these devices are more vulnerable to information security risks; issues such as untested software components, limited battery life and other shortcomings. GAO recommends that FDA develop and implement a plan expanding its focus on information security risks which will include four main actions:

Increase its focus on manufacturers' identification of potential unintentional and intentional threats, vulnerabilities, the resulting information security risks, and strategies to mitigate these risks during its PMA review process;
Utilize available resources, including those from other entities, such as other federal agencies;
Leverage its post-market efforts to identify and investigate information security problems; and
Establish specific milestones for completing this review and implementing these changes

While no major public health risks have occurred stemming from these “advanced” devices, the concern still exists. Do you think there is a need for FDA to develop a proactive plan? Or do you think the agency will develop a reactive plan? Let us know what you think below.

Photo Credit: Matteo Paciotti | Photography