Early score fluctuation in double-blind, placebo-controlled studies may affect the reliability of the baseline measurement and adversely affect the eventual study outcome. We examined the effect of early score fluctuation during a 2-week double-blind placebo lead-in period in a phase II, double-blind, placebo-controlled trial of adjunctive s-adenosyl methionine (MSI-195) in MDD subjects who had had an inadequate response to ongoing antidepressant treatment. The overall study failed to meet its specified endpoints. We examined the score trajectories of all placebo-assigned subjects during the double-blind placebo lead-in period and subsequent 6-week treatment period. Placebo-assigned subjects with ≥20% HamD17 or MADRS score fluctuations (improvement or worsening) during the double-blind placebo lead-in period (prior to randomization) had significantly higher rates of placebo response and remission at week 8 compared to subjects with <20% response. A post-hoc analysis of evaluable subjects taken from the ITT population that excluded subjects with ≥20% early score response yielded higher effect sizes for both the HamD17 and MADRS sub-groups and statistical significance for MSI-195 over placebo in the MADRS sub-group (p = 0.012) with an effect size of 0.404. A reliable baseline measure is an asset for signal detection. These post-hoc findings suggest that study designs that anticipate and attempt to manage early response prior to randomization may yield more meaningful outcome data for trials of MDD and possibly other disorders as well.

中文翻译：

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一项主要抑郁症研究中的早期评分波动和安慰剂反应。

双盲，安慰剂对照研究的早期评分波动可能会影响基线测量的可靠性，并对最终的研究结果产生不利影响。我们在MDD受试者的辅助性S-腺苷甲硫氨酸（MSI-195）的II期，双盲，安慰剂对照试验的II期，双盲，安慰剂对照试验中，研究了2周双盲安慰剂导入期间早期评分波动的影响。对正在进行的抗抑郁药治疗反应不足。总体研究未能达到其指定的终点。我们在双盲安慰剂导入期和随后的6周治疗期中检查了所有分配给安慰剂的受试者的评分轨迹。在双盲安慰剂导入期间（随机分组之前），HamD17或MADRS得分波动≥20％（改善或恶化）的安慰剂分配受试者，与< 20％的回应。对ITT人群中可评估受试者的事后分析，排除了得分≥20％的早期受试者，对HamD17和MADRS子组产生了更高的效应值，并且在MADRS子组中，MSI-195的统计学意义高于安慰剂（p = 0.012），效果大小为0.404。可靠的基线测量是信号检测的资产。