Implications of product withdrawal on a post-approval pragmatic trial: The VOLUME study experience.

Introduction: Many clinical trials terminate early due to safety and efficacy concerns, and less often due to unexpected "positive" findings. However, early termination of post-approval (Phase IV) pragmatic randomized trials for commercial reasons is less frequent, may be more complex, and may require added flexibility in closure methods, including short term follow-up. VOLUME was a randomized, open-label, post-approval pragmatic clinical trial (PCT) or large simple trial that terminated early due to product withdrawal.

Acceptable levels for the breathing resistance of respiratory apparatus: results for men over the age of 45.

Tolerance of additional external resistance to inspiration has been investigated in a group of coalworkers older than 45 years. Peak inspiratory pressure, external respiratory work rate, ventilation, and gas exchange were measured, during periods with and without one of four inspiratory resistances, on 41 subjects walking on a treadmill. Minute volume was reduced, breathing frequency was unchanged and oxygen uptake and carbon dioxide elimination were reduced by the presence of resistance.