Was the assessment of outcomes appropriate

Comparing an agent with a long duration of action to one with a short duration can also be challenging. Timolol eye drops are a standard treatment for managing glaucoma. The maximum reduction in intraocular pressure (IOP) occurs after 1-2 hours and then wears off rapidly. Hence, multiple daily applications are required. In contrast, latanoprost is a prostaglandin analog with maximum IOP reduction after 8-12 hours. If the two drugs are to be fairly compared, IOP measurements need to be made at several timepoints over the course of the day. In one study that did compare the two drugs, the timing of the IOP measurements was arranged to favor the newer agent.17 The sponsor decided to delay the 8:00 a.m. morning dose of the timolol drops until after the 9:00 a.m. IOP measurement. Clearly, any IOP-lowering effect of the timolol dose from the previous evening had worn off by that time.

It takes up to 5 days to achieve the full prophylactic effect of warfarin (Coumadin) for thrombosis prevention. A new anticoagulant, ximelagatran (Exanta) reaches therapeutic concentrations within hours. A short-term trial was designed to compare the two agents in patients undergoing surgery for knee prosthesis. The primary combined outcome was mortality plus thromboembolic events over 7-12 days.7 The new drug showed a lower combined event rate -- mostly for asymptomatic distal thrombi -- but the FDA appropriately rejected the trial as an unfair comparison, since warfarin had never been approved for short-term use.

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