Clinical Trials Increase Off-Study Drug Use: A Segmented Time-Series Analysis.

Area of Science:

• Clinical Pharmacology
• Infectious Diseases
• Clinical Trial Design

Background:

• The impact of clinical trial participation on off-study investigational drug use remains largely undescribed.
• The Daptomycin as Adjunctive Therapy for Staphylococcus aureus bacteremia (DASH) trial aimed to evaluate daptomycin's efficacy, but its effect on overall prescribing patterns was unknown.

Purpose of the Study:

• To determine if participation in the DASH clinical trial influenced overall daptomycin prescribing rates at participating study sites.
• To assess the potential for off-target effects of clinical trials on prescribing habits.

Main Methods:

• Retrospective analysis of daptomycin and linezolid use (defined daily doses per 1000 patient-days) over 8 years pre-trial, 31 months during the trial, and 6 months post-trial.
• Utilized segmented linear regression analysis of interrupted time series to evaluate changes in drug utilization.
• Controlled for rates of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections.

Main Results:

• Daptomycin use showed a statistically significant increase of 0.28 DDD per 1000 patient-days per fiscal period following the initiation of the DASH trial (95% CI, 0.03 to 0.52).
• This increase occurred despite low and stable rates of MRSA and VRE infections, suggesting a trial effect rather than a clinical need.
• Linezolid use remained stable throughout the study periods, and daptomycin use returned to baseline after trial completion.

Conclusions:

• The DASH trial, despite being a negative study, significantly impacted local prescribing habits for daptomycin during its recruitment phase.
• Clinical trial investigators must consider potential off-target effects on drug utilization.
• Prescribers should exercise caution regarding the early adoption of interventions before definitive study results are available.