Clinical Research, Merck Sharp & Dohme Corp,, Whitehouse Station, NJ 08889, USA.
BMC Musculoskelet Disord. 2011 Jul 18;12:165. doi: 10.1186/1471-2474-12-165.
Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT) are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improvement and the associated NNTs.
This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387) comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation.
For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks.
For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30%) improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen. Use of NNTs and responder analyses provide additional, complementary information beyond population mean responses when assessing efficacy compared to placebo and amongst active therapies.
临床镇痛试验通常报告群体平均结果作为疗效指标。然而，研究表明，少数患者属于平均水平，大多数患者的疗效处于极端情况。此外，群体平均结果无法反映疗效水平，因此在个体水平上代表获益-风险的价值有限。应答分析和需要治疗的人数（NNT）被认为更能评估治疗反应。我们评估了镇痛反应水平和 Bath 强直性脊柱炎疾病活动指数（BASDAI）评分改善程度，以及相关的 NNT 值。
这是一项为期 6 周、随机、双盲研究（N=387）的事后分析，比较了依托考昔 90mg、依托考昔 120mg、萘普生 1000mg 和安慰剂在 AS 中的疗效。脊柱疼痛和 BASDAI 采用 100mm 视觉模拟量表进行测量。计算并比较了 BASDAI 和脊柱疼痛均达到≥30%和≥50%改善的患者人数和百分比，以确定相应的 NNT 值。因任何原因退出研究的患者，在退出后 7 天内，其疗效被归为零改善。
对于依托考昔 90mg、依托考昔 120mg 和萘普生 1000mg，与安慰剂相比，6 周时 BASDAI≥30%改善的 NNT 值分别为 2.0、2.0 和 2.7，≥50%改善的 NNT 值分别为 3.2、2.8 和 4.1。对于脊柱疼痛，NNT 值分别为 1.9、2.0 和 3.2，≥30%改善；2.7、2.5 和 3.7，≥50%改善。依托考昔与萘普生之间的差异超过了描述为疼痛有临床意义差异的±0.5 单位的限制。反应率和 NNT 值在 2、4 和 6 周时通常相似且稳定。
每 2 例接受依托考昔治疗的患者中，就有 1 例脊柱疼痛和 BASDAI 达到了超过安慰剂预期的临床显著（≥30%）改善，而接受萘普生治疗的患者中，约每 3 例有 1 例达到这一效果。与安慰剂相比，在评估疗效时，与群体平均反应相比，使用 NNT 和应答分析可提供额外的、互补的信息；与活性治疗相比，NNT 和应答分析也可提供额外的、互补的信息。
