Tag Archives: icardiac

eCOA in action: Podcast interview with iCardiac CEO, Alex Zapesochny

from-rbj-article-headshot-21

Alex Zapesochny, CEO, iCardiac Technologies

Electronic clinical outcome assessment (eCOA) platforms collect data from patients, clinicians and caregivers to make clinical trials more efficient and accurate. iCardiac Technologies, an innovative core lab where I am a board member, just introduced its QPoint eCOA platform to complement its existing cardiac safety and respiratory function product lines.

In this podcast interview, iCardiac CEO Alex Zapesochny shares more about the launch.

  • (0:11) What are some of the key trends you are following in clinical drug development?
  • (1:04) You started with cardiac safety testing and then added pulmonary function testing. How do those fit together?
  • (3:00) Now you have a new platform, QPoint. What is it, and why is it the next logical service?
  • (4:44) For those who are less familiar with eCOA, what is it? And what are some of the challenges that are typically encountered?
  • (7:09) Compliance is often an issue with patient reported outcomes. Do you address compliance with QPoint?
  • (10:30) How important is eCOA for drug development? Is it a major change or incremental?
  • (12:20) You have explained the move from cardiac safety to respiratory to eCOA. What can we expect next from iCardiac?

By healthcare business consultant David E. Williams, president of Health Business Group.

Is Generally Regarded as Safe (GRAS) safe enough?

ID-10072764

What did I eat?

Unlike most people exposed to the Frontline investigation of supplements and vitamins, I really didn’t find it shocking that a lot of supplements are dangerous and that the bottles don’t contain what they say they do. I feel sorry for people who take these products and are not helped –and are even harmed– but frankly the customers should know better.

The story got me thinking about a related topic: the safety (or lack thereof) of food additives. An NPR story from last year (Why the FDA has never looked at some of the additives in our food) sums it up well:

Companies have added thousands of ingredients to foods with little to no government oversight. That’s thanks to a loophole in a decades-old law that allows them to deem an additive to be “generally recognized as safe” — or GRAS — without the U.S. Food and Drug Administration’s blessing, or even its knowledge.

The loophole was originally intended to allow manufacturers of common ingredients like vinegar and table salt — when added to processed foods — to bypass the FDA’s lengthy safety-review process. But over time, companies have found that it’s far more efficient to take advantage of the exemption to get their products on shelves quickly. Some of these products contain additives that the FDA has found to pose dangers. And even ingredients the agency has agreed are GRAS are now drawing scrutiny from scientists and consumer groups that dispute their safety.

Basically companies have been declaring their own products as GRAS. Sometimes they let the FDA know and sometimes not. Since the GRAS concept was introduced during the Eisenhower administration the number of additives in food has gone from around 800 to over 10,000. Chances are you eat GRAS substances every day.

The FDA review process for food is cumbersome, which is a deterrent to undertaking it. But some safety testing is becoming radically less expensive and more reliable. One area I know about is cardiac safety, thanks to my role on the iCardiac Technologies board. Until recently, drugs in development were assessed for cardiac safety by a highly manual and expensive process of measuring QT prolongation. Now iCardiac’s Early Precision QT approach can provide definitive results with a much smaller and more affordable study and it is becoming the standard that is endorsed by FDA and international bodies.

So with the new approach, maybe it’s time to reconsider the cost/benefit of cardiac safety testing at least for certain food additives.

FDA’s “threshold of concern” is reached when a drug extends the QT interval by 10 milliseconds (ms). As it turns out, some food ingredients can reach or exceed this level. For example:

  • An American Heart Association study found that energy drinks could boost QT by 10 ms.
  • Licorice (also used as a sweetener in some products) can lead to long QT when “abused”
  • Ginseng can increase QT by 15 ms.

Some of the more responsible companies like Cargill are undertaking safety studies for new products. Cargill has been evaluating a new sweetener (3000x as sweet as fructose!) derived from root bark. After some initial concerns were unearthed, the company conducted a QT study to determine the ingredient’s safety. As it turned out, this ingredient was found to cause a 20+ ms prolongation of the QT interval, which will certainly give Cargill pause before continuing development. Results of the study (Detection of ECG effects of (2R,4R)-monatin, a sweet flavored isomer of a component first identified in the root bark of the Sclerochitin ilicifolius planthave been published in Food and Chemical Toxicology.

With new techniques, you don’t have to be Cargill to be able to afford to test food ingredients for safety. As consumers become more discerning it will become a good business decision to test more thorougly.

Image courtesy of David Castillo Dominici at FreeDigitalPhotos.ne

By healthcare business consultant David E. Williams, president of Health Business Group.

 

ICH endorses a faster, less expensive approach to cardiac safety testing

iCardiac CEO Alex Zapesochny

iCardiac CEO Alex Zapesochny

Drug developers must demonstrate that new medications are safe and effective in order to win regulatory approval. The gold standard in cardiac safety testing has been the Thorough QT study, a separate, expensive trial that is typically conducted late in the clinical development process.

The international body that informs drug development standards has just revised its stance to support definitive QT testing based on ECGs collected during existing early-stage trials. iCardiac Technologies, where I’m a board member, pioneered this approach in conjunction with the FDA. I asked iCardiac’s CEO Alex Zapesochny to explain what is happening.

  1. What is the ICH and why does it matter for clinical trials?

The International Council for Harmonisation is an international forum for regulators to harmonize drug approval practices. The group includes pharmaceutical industry representatives and regulators from the United States, Canada, the European Union, Japan and Switzerland.

As for the clinical trials process, the ICH aims to make recommendations toward achieving greater harmonization in the interpretation and application of technical guidelines and requirements related to research and development of new drugs. These guidelines can assist with pharmaceutical product registration and help reduce or avoid duplication of testing carried out during R&D.

  1. ICH has issued a regulatory revision for cardiac safety testing. What specifically has it done?

Currently, the FDA and other regulators expect nearly all new drugs to be tested using a costly, stand-alone Thorough QT (TQT) study to assess a drug’s effect on the QT interval before market approval. This is an important step, since a prolonged QT interval is associated with a heightened risk for arrhythmias and possible sudden cardiac death. The latest revision adopted by the ICH states that data from ECGs collected during routine Phase I or other early clinical trials may be used to conclusively demonstrate a drug’s QT effect. This approach relies on intensive, high quality ECG analysis and the use of exposure response modeling.

  1. What led to the change?

Regulators around the world want to make the drug development process as safe, precise and efficient as possible. The ICH revision emerged a year after the U.S. Food and Drug Administration helped to organize a meeting of thought leaders to discuss the results of a successful prospective validation study demonstrating the ability to determine cardiac safety much earlier in the development process. This revision is likely the most significant regulatory shift in cardiac safety since the original E14 guidance was adopted by the ICH in 2005.

  1. What role did iCardiac play? The FDA?

iCardiac has been championing this alternative approach for several years, including collaborating with thought leaders from the FDA and from industry to help organize a prospective validation study to definitively test this new approach. Ultimately iCardiac sponsored that definitive validation study, and it was overseen by iCardiac personnel and used our proprietary High Precision QT methodology to perform the critical data analysis. Leaders from the FDA have been involved in multiple key ways, including decisions around the validation study design and co-authoring publications about the validation study and its implications. Of course, the FDA is also a participant in the ICH and played a direct role in the new regulatory revision.

  1. What will be the practical implications?

This development provides an alternative path for sponsors with regard to demonstrating the effect of their drug on QT, which is a critical part of gaining market approval for a new drug. By analyzing ECG data from a Phase I or other early clinical study, sponsors can choose to seek a waiver from regulators from having to do a TQT study. The FDA granted the first TQT waiver based on this alternative approach earlier in 2015. So apart from saving time and money, this approach gives drug developers insight into their compound’s QT liability much earlier in the clinical trials process.

  1. What are you doing to let people know more about the implications?

iCardiac will conduct two free public webinars to explain the new ICH guidance and the standards it establishes for receiving a waiver from the Through QT study. Dr. Borje Darpo, a cardiologist and chief scientific officer at iCardiac, will discuss the impact of this regulatory revision on the clinical development process. The webinars will be held on January 12th and January 20th, 2016. You can follow the links below to register for one of iCardiac’s webinars:

By healthcare business consultant David E. Williams, president of Health Business Group.