Survey Reveals Reasons Why Respondents Avoid AATD Trial Participation

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A survey found individuals may avoid participating in AATD trials because a trial may require them to go off augmentation therapy.

A survey pinpointed reasons why respondents avoid alpha-1 antitrypsin deficiency (AATD) trial participation, with the top reason being people not wanting to be required to halt augmentation therapy for 12 months.1

The survey aimed to examine the characteristics of clinical trials that encourage or discourage participation interest among individuals with AATD. The survey was also intended to identify the demographics and health characteristics of individuals who have a high level of interest in trial participation. Investigators, led by Kristen E. Holm, PhD, MPH, from National Jewish Health, conducted this cross-sectional, self-report survey to improve AATD clinical trial designs.

“This study is the first to systematically examine potential barriers to trial participation among individuals with AATD,” investigators wrote.

A previous study identified augmentation therapy as a barrier to AATL trial participation but did not quantify the extent.2

Holm and colleagues invited individuals with AATD on augmentation therapy from the Alpha-1 Disease Management and Prevention Program (ADAMAPP) and individuals with severely deficient AATD with no augmentation therapy from the Risk Evaluation to Achieve Continued Health (REACH) to participate in the study.1

Investigators divided participants into 3 age categories: ≤ 52, 53 – 64, and≥ 65 years. They determined these cut points since age 53 is when the onset of chronic obstructive pulmonary disease may occur and age 65 is when individuals become eligible for Medicare.

The survey asked respondents about their employment status, whether they have been diagnosed with liver or lung disease, use augmentation therapy, and regularly use supplemental oxygen. The survey assessed the frequency of exacerbations of lung problems and hospitalizations for lung or liver disease.

Respondents ranked 34 aspects of clinical trials 1 – 5 (1: would not participate; 5: highly interested in participants). Examples of items ranked included: trial with 3 liver biopsies, trial with 3 bronchoscopies, use of placebo, changes to existing therapy, change of getting a placebo instead of an active study drug, the study requires 12 months off of augmentation, some visits are by telemedicine, and travel to the research site would require an airplane ride.

In total, 1664 respondents were included in the analysis, with 91.6% diagnosed with lung disease, 16.3% diagnosed with liver disease, and 14.9% diagnosed with both lung and liver disease. Half of the respondents (50.6%) were aged ≥ 65 years, followed by 34.3% aged 53 – 64 years and 15% aged ≤ 52 years. Most of the sample was non-Hispanic White (97.2%), and more than half (58.4%) were female.

Results of the Survey

The survey showed participants are more unlikely to participate in a study with more liver biopsies. Only 11.7% of participants responded they would participate if there were no liver biopsies, and the percentage jumped with 1 liver biopsy (32%), 2 liver biopsies (43.3%), and 3 liver biopsies (53.3%). The team saw similar responses for bronchoscopies, with 13% stating they would not participate in a study with no bronchoscopies, 25.5% would not participate with 1 bronchoscopy, 33.7% would not participate with 2 bronchoscopies, and 44% would not participate with 3 bronchoscopies.

Less than a quarter (32% of respondents stated they would not participate in the trial if there were a possibility they would get a placebo instead of an active study drug.

A high percentage of participants (69.6%) responded they would not participate if a trial required 12 months off of augmentation therapy. If the trial required 1 or 6 months off therapy, 29.3% and 54.6% would not participate, respectively.

More than one-third of participants stated they would be highly interested in participating in a trial that has a pill (35.8%) or a drug that is inhaled (32.7%) as a study drug. Participants were less interested if the drug was intravenous with only 21.7% highly interested in participating.

Furthermore, respondents are more highly interested in participants when it is virtual (38.3%), followed by some visits by telemedicine (28.4%) and all visits in person (10.2%). Many participants would not participate in a study if they had to take a plane (50.9%), drive over 2 hours (39.9%), and stay overnight (31.9%).

Investigators saw individuals diagnosed with liver disease and lung disease had greater odds of being in the high-interest group (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1 – 1.9; P = .016 and OR, 1.6; 95% CI, 1.1 – 2.4; P = .028).

Individuals were also more likely to be in the high-interest group if they had a CAT score ≥ 10, had ≥2 exacerbations in the previous year, and had an mMRC score ≥ 3. Additionally, individuals ≥ 52 were more likely to participate in clinical trials than those under ≤ 52.

“Given the limited number of individuals available to participate in clinical trials for medications to treat lung or liver disease due to AATD, it is important to develop clinical trials in which potential participants are willing to enroll,” investigators concluded. “This will make it easier for trials to meet recruitment targets and therefore draw reliable conclusions regarding the efficacy and safety of potential new medications.”


  1. Holm KE, Sandhaus RA, Allison S, Strange C. Clinical trial attitudes among individuals with Alpha-1 antitrypsin deficiency. Respir Med. Published online May 23, 2024. doi:10.1016/j.rmed.2024.107676
  2. Schluchter MD, Stoller JK, Barker AF, et al. Feasibility of a clinical trial of augmentation therapy for alpha(1)-antitrypsin deficiency. The Alpha 1-Antitrypsin Deficiency Registry Study Group. Am J Respir Crit Care Med. 2000;161(3 Pt 1):796-801. doi:10.1164/ajrccm.161.3.9906011