Modeling the disruption of respiratory disease clinical trials by non-pharmaceutical COVID-19 interventions.
Nat Commun
; 13(1): 1980, 2022 04 13.
Article
in English
| MEDLINE | ID: covidwho-1788287
ABSTRACT
Respiratory disease trials are profoundly affected by non-pharmaceutical interventions (NPIs) against COVID-19 because they perturb existing regular patterns of all seasonal viral epidemics. To address trial design with such uncertainty, we developed an epidemiological model of respiratory tract infection (RTI) coupled to a mechanistic description of viral RTI episodes. We explored the impact of reduced viral transmission (mimicking NPIs) using a virtual population and in silico trials for the bacterial lysate OM-85 as prophylaxis for RTI. Ratio-based efficacy metrics are only impacted under strict lockdown whereas absolute benefit already is with intermediate NPIs (eg. mask-wearing). Consequently, despite NPI, trials may meet their relative efficacy endpoints (provided recruitment hurdles can be overcome) but are difficult to assess with respect to clinical relevance. These results advocate to report a variety of metrics for benefit assessment, to use adaptive trial design and adapted statistical analyses. They also question eligibility criteria misaligned with the actual disease burden.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Respiration Disorders
/
Respiratory Tract Infections
/
Virus Diseases
/
COVID-19
Type of study:
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2022
Document Type:
Article
Affiliation country:
S41467-022-29534-8
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