Reply to Callahan: Identifying “Real” Patients in the Real World

From the Authors:

We thank Dr. Callahan for his letter regarding our recent publication on the clinical effectiveness of pirfenidone and nintedanib for patients with idiopathic pulmonary fibrosis (IPF) (1). We appreciate his remarks on our methodology, and agree that controlling for index treatment site (academic vs. community practice) would be a valuable addition to the literature. Unfortunately, as with all retrospective studies, our analysis was limited by the confines of the dataset we used. Although our data allow for subgroup analysis by region, they do not allow for separation by the granular geographic detail necessary to divide the cohort into patients with IPF treated in academic centers and those treated in community practice. Our hope is to analyze the effectiveness of these medications again with a Medicare fee-for-service cohort, which would allow for treatment variation analyses by entities such as “hospital referral regions,” a methodology that has allowed for the study of geographic differences and academic medical center practice variation in the past (2, 3).

We also endorse his support for treatment initiation in consultation with disease experts, as well as the importance of multidisciplinary discussions to confirm the diagnosis of “true” IPF—practices that have been corroborated by many of the recent guidelines and literature (4, 5). As acknowledged in our article, the diagnosis of IPF can be clinically challenging, which then makes the use of billing codes in this population quite complex and susceptible to some degree of misidentification. With the local cohort validation, we believe we were able to identify a population largely consisting of patients with “true” IPF, although (as described) miscoding is still possible.

The potential for misidentification is perceptively highlighted by Dr. Callahan in his identification of the proportion of patients in our cohort with rheumatoid arthritis (RA). Although we agree that the patients with concomitant RA in the cohort make alternative diagnoses possible, the number is small enough that it should not affect the overall analysis. In addition, patients with RA and a usual interstitial pneumonia pattern on imaging (as is likely for those in our cohort, given their coded diagnosis of IPF) have been shown to have mortality similar to that observed in those with “true” IPF, which makes it even more unlikely that the outcomes were modified by the less than 9% of individuals in the cohort with RA (6).

Once again, we thank Dr. Callahan for his letter and very much appreciate his discussion about the value of multidisciplinary teams when diagnosing IPF, and his advocacy for an analysis comparing academic medical centers and community practices when determining the effectiveness of pirfenidone and nintedanib. We look forward to further studies evaluating these and other important questions surrounding the antifibrotic medications for patients with IPF.