PMID- 34735756
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220406
IS  - 2372-952X (Print)
IS  - 2372-952X (Electronic)
IS  - 2372-952X (Linking)
VI  - 9
IP  - 1
DP  - 2022 Jan 27
TI  - Designing Clinical Trials in "Regular" COPD Versus Alpha-1 Antitrypsin 
      Deficiency-Associated COPD: "More Alike Than Unalike?".
PG  - 95-102
LID - 10.15326/jcopdf.2021.0261 [doi]
AB  - Alpha-1 antitrypsin deficiency (AATD) predisposes to emphysema, liver disease, 
      and panniculitis. This emphysema risk naturally invites a comparison between 
      "regular" chronic obstructive pulmonary disease (COPD) (i.e., unrelated to AATD) 
      and AATD-associated emphysema. Several features characterize both conditions. 
      Both can be life-limiting and highly debilitating. Both are highly 
      under-recognized. An important corollary of this comparison between "regular" 
      COPD and AATD-associated COPD is whether both should be treated similarly and 
      whether clinical trials to assess new therapies can be conducted similarly in 
      both. Here, the distinctions between "regular" COPD and AATD-associated COPD are 
      quite pronounced. Therapeutically, sparse available data suggest that lung volume 
      reduction surgery confers less improvement in forced expiratory volume in 1 
      second (FEV1) in AATD and that such benefits are shorter-lived. Perhaps the most 
      striking contrast between the 2 conditions is that clinical trial designs and 
      conduct are necessarily very different. The relative scarcity of diagnosed 
      individuals with AATD hampers recruitment to trials. Furthermore, primary outcome 
      measures in trials of "regular" COPD must differ markedly from those of 
      AATD-associated emphysema. Specifically, power calculations show that FEV1 and 
      exacerbation frequency, which are amply represented as endpoints in large COPD 
      trials, are infeasible in studies of AATD-associated emphysema. Rather, in the 3 
      available randomized controlled trials of intravenous augmentation therapy, the 
      rate of emphysema progression based on serial computed tomography densitometry 
      measurements has been the only feasible primary outcome measure. These 
      considerations underscore the distinctive challenges and needs of conducting 
      treatment trials in AATD-associated emphysema and emphasize that, with regard to 
      clinical study design, the 2 conditions are "more unalike than alike."
CI  - JCOPDF (c) 2021.
FAU - Stoller, James K
AU  - Stoller JK
AD  - Education Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Chronic Obstr Pulm Dis
JT  - Chronic obstructive pulmonary diseases (Miami, Fla.)
JID - 101635411
PMC - PMC8893971
OTO - NOTNLM
OT  - alpha-1 antitrypsin deficiency
OT  - clinical trials
OT  - copd
OT  - endotype
COIS- Dr. Stoller serves as a member of the Board of Directors of the Alpha-1 
      Foundation and as a consultant to: 23andMe, Grifols, Takeda, CSL-Behring, 
      InhibRx, Arrowhead Pharmaceuticals, Dicerna, Insmed, Vertex, 4DMT, Korro, and 
      Bridgebio.
EDAT- 2021/11/05 06:00
MHDA- 2021/11/05 06:01
PMCR- 2021/11/03
CRDT- 2021/11/04 17:38
PHST- 2021/11/05 06:00 [pubmed]
PHST- 2021/11/05 06:01 [medline]
PHST- 2021/11/04 17:38 [entrez]
PHST- 2021/11/03 00:00 [pmc-release]
AID - 10.15326/jcopdf.2021.0261 [doi]
PST - ppublish
SO  - Chronic Obstr Pulm Dis. 2022 Jan 27;9(1):95-102. doi: 10.15326/jcopdf.2021.0261.