Risk factors for subject withdrawals in clinical trials evaluating glaucoma medications.

BACKGROUND

To evaluate risk factors for subject withdrawals from multicenter clinical trials evaluating glaucoma medications.

METHODS

An analysis of prospective, randomized, multicenter, parallel, active-controlled clinical trials with 70 subjects/treatment arm published from 1996-2008.

RESULTS

We analyzed 36 glaucoma studies including 17,511 subjects at 1,294 clinical sites. There were 2,060 (12%) subject withdrawals with 669 (32%) for administrative errors, 945 (46%) for adverse events (AEs), 197 (10%) for inadequate intraocular pressure (IOP) control and 249 (12%) for unknown reasons. By multilinear regression analysis, no positive risk factors for early subject withdrawals were observed following a Bonferroni correction (p > or = 0.01). A positive correlation was observed for medication errors and protocol violations to withdrawals due to ocular AEs and total administrative errors (p < 0.0001). Protocol violations alone were correlated to subject withdrawals for any AE (total/month) and systemic AEs (p < 0.0001). Females and Caucasians were correlated to medication errors (p < 0 .0001). Among medical therapies, alpha-agonists, beta-blockers, the carbonic anhydrase inhibitor/beta-blocker fixed combination and prostaglandins were correlated with systemic AEs (p < or = 0.005) while the alpha-agonists were correlated with withdrawals for poor IOP control (p = 0.00056).

CONCLUSIONS

Subject withdrawals from clinical trials for total administrative errors or AEs potentially might be reduced by choosing sites with lower historical rates of protocol violations or medication dispensing errors. Drug class choice also may influence subject withdrawals for AEs and poor IOP control.