AN INSIDE LOOK AT THE LATEST ATS/ERS GUIDELINES
Dawn Patterson, ERT Director of Respiratory Solutions, is joined by Kevin McCarthy, ERT Clinical Overread Specialist and member of the ATS/ERS 2019 Spirometry Update Task Force. They’ll explore the implications of the October 2019 ATS/ERS spirometry update to their pulmonary function testing guidance. ERT was the only data and technology vendor involved in the update.
Access Trial Better Podcast from your favorite channels:
What are the ATS/ERS guidelines? [02:22]
These guidelines represent what can be considered as worldwide standards that ensure the quality of pulmonary function measurements. This type of measurement is somewhat unique in that it requires a high degree of patient understanding and cooperation.
When were the ATS/ERS guidelines last updated?[02:58]
Spirometry standards were first published 40 years ago, and updated approximately every 10-15 years since. The last time they were updated prior to 2019 was 2005.
How did you get involved in the task force that was responsible for updating the guidelines?[03:25]
I was approached by the ATS/ERS to participate on a committee to develop an accreditation for pulmonary function laboratories. While working on that project, I was asked if I’d be interested in participating on the update task force.
How is this guidance used in clinical research?[04:00]
Typically, ATS / ERS guidelines are incorporated in testing protocol for clinical trials. This is important in guaranteeing comparability of tests obtained from multiple global testing sites. In the 2019 guidelines, it’s specified that these standards represent the minimum criteria that must be met for clinical spirometry only – not necessarily for research or occupational surveillance. In clinical trials, sometimes the bar should be set higher.
What are the most important changes in the new spirometry guidelines?[04:39]
One of the most important changes involves the recognition that the forced exhalation could be performed perfectly but still give erroneously low results. The new standards emphasize the need to look at the subject for feedback, and gives detailed guidance to site operators on how to vigorously coach patients to full inflation.
The new standards also stipulate that the procedure does not end with the forced exhalation. At the end of the forced exhalation, the subject is again vigorously coached to full inflation, allowing for a comparison to the FVC that allows operators to verify the forced exhalation started from full inflation.
In recognition that pediatric patients and patients with interstitial lung disease had difficulty in meeting end-of-test acceptability criteria, these acceptability criteria were redefined in a manner that accommodates the lung physiology of these groups.
Finally, the updated standards provide a new letter grading standard for acceptability based on the two main forced spirometry parameters. In the old standards, if an effort failed to meet the start of test criteria, the effort was considered to be unusable for reporting. In the new standards, an effort that is unusable for FEV1 may be acceptable for FVC and vice versa.
Are there any minor changes to the guidance that people need to look out for? [10:39]
This document makes recommendations to the manufacturers about features that they should provide for the users of their testing equipment. One of the recommendations made was that the manufacturers provide standard lists of operator comments. These lists allow the operator to quickly select a comment from a list (in addition to adding free text) to provide insight and context about quality issues for study teams or physicians.
How will this new guidance impact sites and patients in respiratory clinical trials?[12:05]
This new update of the spirometry standards will likely reduce the number of times a patient will have to perform the forced expiratory maneuver to achieve acceptability, improve data repeatability and improve data quality by verifying all efforts start from full inflation. This should result in a big win for sponsors, especially in studies involving pediatric patients and patients with interstitial lung disease.
There was an increased recognition of the importance of the operator administering the test in getting quality results. Operator training and the attainment and maintenance of competency must be integrated in any spirometry testing service.
Intro: Welcome back to ERT’s Trial Better Podcast Series. In today’s episode, we’ll be reviewing the 2019 updates of the ATS ERS guidelines. We’ll dig deep into the critical guideline changes, how the updates will impact clinical research and how patients will benefit from the new guidance. To help us explore these updates, we are lucky to have one of the document’s co-creators, Kevin McCarthy and leading today’s discussion is ERT’s Director of Respiratory Solutions, Dawn Patterson. So, let’s not waste time and dive into this instalment of the Trial Better podcast.
Dawn Patterson: Welcome to ERT’s Trial Better Podcast Series. I’m Dawn Patterson, Director of Respiratory Solutions at ERT, filling in for your usual host, Jason Egger. On today’s episode, we’re taking a look at ATS ERS updates, to their guidance for pulmonary function testing, which hasn’t changed since 2005. I’m joined by my ERT colleague, Kevin McCarthy, who was a member of the 2019 ATS ERS Spirometry Update Task Force. Kevin, welcome to Trial. Better.
Kevin McCarthy: Thank you. Glad to be here.
Dawn Patterson: Kevin, can you tell us about your background in respiratory research?
Kevin McCarthy: Certainly! I’ve been working in the field of Pulmonary Function Testing since 1973. My experiences with clinical research comes from three different points of view; first as a Pulmonary Function Technologist at Cleveland Clinic, I administered pulmonary function tests to patients participating in clinical trials. In that context, my goal was to obtain the highest quality measurement possible. Then I was appointed manager of the Pulmonary Function Laboratories at Cleveland Clinic where we had as many as 30 or 40 different clinical trials ongoing in our laboratories at any given time. My job then was to see that the operators collecting those pulmonary function measurements, were adhering to the protocol agreed upon for any different given study. And once again, high quality measurements remained the goal. And finally working for ERT as a Clinical Specialist and Overread, my job was to review measurements with respect to adherence to the ATS /ERS standards and study protocol standards and to make recommendations for quality improvement.
Dawn Patterson: Kevin, for everyone’s background, what are the ATS ERS guidelines?
Kevin McCarthy: Good question. The ATS ERS guidelines for pulmonary function measurements represent what can be considered as worldwide standards, that if followed, ensure the quality of pulmonary function measurements. Pulmonary function measurements are somewhat unique amongst other diagnostic tests in that most require a high degree of patient understanding and cooperation. Unlike blood tests, for example, if the patient does not cooperate fully with high quality instructions and coaching erroneous results can be produced.
Dawn Patterson: Thank you. Kevin, when were the guidelines last updated and why were they updated in 2019?
Kevin McCarthy: Okay, good question. So, the spirometry standards and actually spirometry was the first set of standards that were published by the ATS. They were first published 40 years ago, and they’ve been sort of updated every 10 or 15 years. And the last time they were published before 2019 was 2005.
Dawn Patterson: You worked on the task force that updated the new guidelines. How did you get involved?
Kevin McCarthy: Well, I retired from Cleveland Clinic in 2016 and had been asked by the ATS to participate on a committee to develop an accreditation program for pulmonary function laboratories. While working on that project, I was asked if I would be interested in participating on the task force to update the standards for spirometry testing. And of course, I was very interested knowing the importance of that document and it kind of felt like I was leaving my final mark on the industry.
Dawn Patterson: How has the guidance used in clinical research?
Kevin McCarthy: So, the ATS guidelines are incorporated typically in the testing protocol for clinical trials. This is important for guaranteeing comparability of test results obtained from multiple testing sites across the globe. There is an important statement in the new standards that says these guidelines represent the minimum criteria that must be met for clinical spirometry, which may not be sufficient for all settings such as research or occupational surveillance. In the clinical trial world, sometimes the bar should be set higher.
Dawn Patterson: Absolutely. After reading the guidelines, there were a few changes, major changes. Can you tell me about the top three changes in the spirometry guidelines?
Kevin McCarthy: So of course, this is just my opinion, but one of the most important changes involves the recognition that if the forced exhalation starts from a lung volume below full inflation, it could be performed perfectly and give erroneous lower results. This was often the cause for poor repeatability between efforts in a measurement. The new standards now emphasize the need for the operator to look at the subject when coaching the inhalation to full inflation for feedback indicating that the subject really is at full inflation, before they give the command to start the forced exhalation.
Guidance and detailed guidance is given to the operators on how to vigorously coach patients to full inflation and what feedback to look for. Further, the new standards stipulate that the procedure doesn’t end with the end of the forced exhalation. Now at the end of the forced exhalation, the subject is again vigorously coached to full inflation. The volume inspired after they’ve completed the forced exhalation is compared to the forced vital capacity that was just measured, to verify that the forced exhalation started from full inflation. The FVC from an effort should closely match the volume inspired to full inflation after the forced exhalation is completed. This is a major new addition to the spirometry procedure and it’s going to take a little while for the world to get used to that, but I think with good benefit. Starting each effort from full inflation should reduce the variability between efforts within the measurement session and will likely reduce the number of efforts that patients will have to do to meet the acceptability and repeatability criteria.
Dawn Patterson: So, Kevin, before you move on, I just have a question about that. So, it’s really important the operator really coaches the subject, correct?
Kevin McCarthy: Yes, yes. So, my experience and I saw this, with the operation that I left at Cleveland Clinic was fairly large when I left. We had over 30 laboratories there, and when I trained people, and in particular people that actually came to me with PFT experience were amongst the worst, that they were used to delivering the instructions, the coaching as it were in a very standardized fashion and often neglected to look at the patient. They would just kind of give the same set of instructions, okay take in a deep breath, deep breath, deep breath and blow.
And rather than looking at the patient to see some of the telltale signs that they really were at full inflation, they would just kind of do the same rote set of instructions over and over again. And the repeatability was really dependent upon how well the patient responded, were they doing it in the same degree of, were they inspiring at the same flow rate? And even then, if they achieve repeatability, oftentimes it really wasn’t full inflation, that the best effort represented. It was just the biggest out of all of them that they did, and they happen to hit it in the context of doing aid efforts. They would hit two that were repeatable and the other six oftentimes we’re not even close. It’s really, really important and that’s why you’re going to see that it’s stressed in that document so strongly.
So, going on, there’s another important change that basically one of the things that the task force does is it takes a look at the literature that was published regarding spirometry since the last set of standards was published. And there were some papers they were published that expressed dissatisfaction with what were called the end of test criteria. Specifically, that there were in the pediatric population and in patients with interstitial lung disease, it was found that they had difficulty meeting the previous end of test criteria for acceptability. The old standards said two criteria had to be met for the end of test to be considered acceptable. A minimum expiratory time of six seconds and no volume change for the last second of exhalation had to be demonstrated. And it turns out that achievement of both these criteria is difficult for patients with high lung elastic recoil to achieve.
That’s the patients that are very, very young and those whose lungs have sort of stiffened up because of interstitial changes. So, the acceptability criteria for the end of the forced exhalation was redefined in a manner that accommodates the physiology of these two important patient populations. And finally, I think this is one of the more important changes as well, is that there was a recognition that the previous definition for what constituted an in acceptable effort often resulted in throwing out the baby with the bathwater.
What I mean by that is that an effort where the start of test criteria was not met would be labeled unacceptable, even though the end of test criteria indicated that the FVC was absolutely valid. But we were sort of prevented from reporting that particularly in the world of clinical trials. The converse was also a true, efforts that failed to meet the end of test criteria were considered to be unacceptable and could not be used for reporting the FEV one, which may be absolutely acceptable. So, the new standards propose a separate grading system for both FVC and FEV one. An effort that is unusable for FEV one may be acceptable for FVC and vice versa. This should have the effect of reducing the number of efforts that patients have to perform to achieve an acceptable measurement.
Dawn Patterson: That’s great. There were some major changes.
Kevin McCarthy: Yes, a lot of discussion about that, and as I said, the literature really guided our hands. So, we relied on the work of people who were frustrated by the fact that the standards that they had to be held to really weren’t accommodating the patient population that they were testing.
Dawn Patterson: Wonderful. So, besides the major changes, were there any other minor changes of this document?
Kevin McCarthy: Yes, yes there were. So, one of the things that this document does, and it did it in previous versions of the standards as well, is to make recommendations to the manufacturers about features that they should provide for their users of their testing equipment. And one of the recommendations in this document is the recommendation that the manufacturers provide standardized lists of operator comments. It’s very common in the clinical world and the clinical trial world to see the comment, good effort.
Dawn Patterson: Right.
Kevin McCarthy: Be assigned to a measurement where there’s clear technical flaws. And so, this kind of obviates the purpose of what the comments technician comments are supposed to provide. They’re supposed to give the ordering or interpreting physician or the clinical trial sponsor teams some insight about test quality issues in that measurement. And so those standardized lists go a long way to allow the operator to quickly select the appropriate comment from a list. And the recommendation is of course to continue to provide the ability for operators to enter free text, if they feel that in the situation that they have at hand isn’t described by any of the entries in that standardized list.
Dawn Patterson: We know collecting data in the diagnostic world is different than the clinical trial world. Can you let us know the new guidelines and how it’s going to impact those patients in a clinical trial?
Kevin McCarthy: Sure. If the guidelines are followed, the new standards will likely improve data acceptability and repeatability. And that is, I think that the one recommendation that we changed the procedure to allow verification that the patient was at full inflation. That’s going to likely allow the operator to get the patient to full inflation quicker and allow them to ensure that they reach that point with every effort. And that should reduce the overall number of efforts that the patients have to do before the operator feels that they have the best measurement that they can obtain.
That’s a big, big win for patients because in clinical trial world, sometimes particularly if you’re trying to demonstrate how the drug is, what effect the drug is having over time, those patients are there for eight to 12 hours sometimes, doing repeated measures of this forced vital capacity maneuver over and over and over again. And that can be really exhausting, and so if they’re doing the maximum number of efforts at each one of those single measurements, for example, that patient’s likely to be exhausted by the end of the day. And if after the first couple of measurements the patient gets it, it often results in them doing only three efforts, getting the three acceptable efforts that are required to say that this measurement is acceptable. That’s a big win.
Dawn Patterson: That is a big win Kevin, thank you, Kevin, are there any final thoughts?
Kevin McCarthy: Yes, yes and this is I think a big one. Everybody on the task force agreed that there was an increased recognition or the need for an increased recognition, that the operator is critically important. The person administering the test is critically important to getting good, high quality results. Operator training and the attainment and maintenance of competency must be documented and integrated into any spirometry testing service. And in my opinion, this recognition of the importance of training and maintenance of competency will help overcome the unfortunate yet pervasive notion that one needs only to learn what buttons to push to produce high quality spirometry measurements. And I think that’s one of the challenges we see in clinical trials is that oftentimes the people involved in the clinical trial management feel that like, oh just show what buttons to push and they’ll be okay. I think it goes, well we know it goes much, much farther than that and hopefully this is going to help other people that aren’t doing testing recognize that there’s a little bit more to it than just pushing the buttons and saying the words.
Dawn Patterson: Kevin, thank you so much for stopping by the Trial, Better Podcast and for sharing your insight on the new guidelines and how we can leverage on the new spirometry updates. Also want to thank you and the task force for all the hard work you put in over the last two years. I also want to thank the listeners for tuning in and as always, feel free if you have any questions to reach out to [email protected] Thanks again and see you later.
Outro: Thanks to Dawn and Kevin for reviewing the 2019 updates to the ATS ERS guidelines and thank you the listeners for tuning into this episode of Trial Better. Have a question for Kevin or Dawn, please let us know by sending us a message to [email protected] Thank you again for tuning in and we’ll see you next time on the Trial Better Podcast.
Kevin McCarthy, RPFT
Respiratory Overread Clinical Specialist, ERT
Member, American Thoracic Society (ATS)/European Respiratory Society (ERS) 2019 Spirometry Update Task Force
Kevin McCarthy has worked in the field of pulmonary function testing for over four decades. He currently serves as a Respiratory Overread Clinical Specialist at ERT. Previously, McCarthy was a Manager of the Pulmonary Function Laboratories at the Cleveland Clinic for 38 years, has written numerous publications in the field of pulmonary function testing and has extensive research experience. He is a member of the ATS Proficiency Standards for Pulmonary Function Laboratories Committee and served as a member of the joint ATS/ERS task force that updated spirometry standards in 2019