The largest source of subject variability within a respiratory clinical trial is the improper performance of a test. Such “noise” in spirometry and other pulmonary function testing (PFT), coupled with device calibration and technician training inconsistencies, can restrict the ability to find important clinical signals relating to treatment effects.
For your trial, this means a heightened risk of inaccurate and unusable data that can only be prevented by utilizing standardized and centralized respiratory services. Standardization involves the use of consistent devices and calibration across sites, as well as identical training regimes for technicians to ensure consistent patient performance. Centralization delivers digital collection of test results and helps increase data quality by providing the ability to better see treatment effects through accurate analysis. Centralization also institutes quality control measures in each step of the clinical trial process so the study has the advantage of cleaner data, which in turn minimizes the negative impact to your data and your budget.
These benefits apply to the carbon monoxide diffusing capacity test (DLCO), a commonly used pulmonary function test that measures the gas exchange ability of the lungs. While spirometry measures lung mechanics and lung volume PFTs ascertain size, DLCO tests indicate how well the lungs and heart are able to oxygenate blood. DLCO measurements specifically test the integrity of the alveolar/capillary interface in the lungs. Repeated measures of DLCO aid in determining disease progression or therapy efficacy and enable clinicians to identify diagnostic details that are not visible by spirometry or other PFT approaches.
Unfortunately, many DLCO measurements are subject to variability as a result of patient, equipment, or technician errors. To obtain consistent, credible data, DLCO equipment must be properly maintained and regularly calibrated. In addition, diffusion testing requires a specially trained technician who can validate the data by understanding the measurements and also their plausibility in relationship to the subject’s condition.
According to a study published in Respiratory Care, DLCO measurements of the same patient in different labs vary as much as 50%. In an effort to reduce these differences, the American Thoracic Society (ATS) and European Respiratory Society (ERS) published the standardized testing procedures and equipment recommendations for DLCO in 2005, which can be found here: http://www.thoracic.org/statements/resources/pfet/pft4.pdf.
Since improper training and poor patient effort will lead to poor quality data, it is crucial to educate and monitor the technicians to improve the accuracy of the data being reported. It is equally important to ensure the equipment and measurement procedures meet performance criteria so that end assessments have the greatest, most consistent data – significantly reducing variability.
Using standard equipment across all investigator sites is also vital to producing consistent, quality data. Standardized devices significantly reduce variability often caused between instruments, meeting ATS/ERS standards for accuracy.
With centralization, data is transmitted to a central database and is graded according to a combination of the ATS/ERS standards and pharmaceutical company specifications. The overread of data quality is reviewed proactively, so sites with a large amount of poor quality data can be targeted during the trial for retraining.
Centralized, standardized DLCO measurement benefits the development of new compounds for the treatment of asthma, chronic obstructive pulmonary disease (COPD), and other indications by reducing variability inherent to effort-dependent pulmonary tests. ERT provides standardized devices and training as well as central data collection, and we will evaluate both digital and site-generated paper DLCO measurements for quality and performance. 100% data overread is provided by a highly qualified team with over 20 years of clinical experience guided by multiple levels of quality control and assurance. Standardizing and centralizing with ERT significantly increases the percentage of acceptable data and provides the best quality data – resulting in greater patient retention, increased statistical power at a reduced price, and ultimate determination of efficacy to support your new drug application’s regulatory approval.
Visit the ERT Resource Center at https://www.ert.com/clinical/resources for more information on centralizing and standardizing DLCO and other measures in respiratory trials. There you can register to view the recently recorded webinar, “Current Pharmacotherapeutic Treatment and DLCO Monitoring Strategies for the Management of Asthma and COPD.”