回歸均值的統計現像是否可以解釋安慰劑的顯著效果以及某些精神藥物的假定有效性？
彼得·西蒙斯-2019 年 4 月 16 日

Michael P. Hengartner 的一篇新文章探討了回歸到平均值的統計現象可能是安慰劑在精神科藥物研究中的顯著影響的原因。 Hengartner是蘇黎世應用科學大學的臨床心理學家，該論文在BMJ Evidence-Based Medicine上提前在線發表。
A new article by Michael P. Hengartner explores the possibility that the statistical phenomenon of regression to the mean may be responsible for the dramatic effects of placebo in psychiatric drug studies. Hengartner is a clinical psychologist at the Zurich University of Applied Sciences, and the paper was published online ahead of print in BMJ Evidence-Based Medicine.

回歸均值是一個統計術語。在該理論下，異常值（在極端情況下）可能會自發地向平均值移動。一個例子說明了這種現象。
Regression to the mean is a statistical term. Under this theory, scores that are outliers (at the extremes) are likely to move toward a more average value spontaneously. An example illustrates this phenomenon.

患有中度抑鬱症的人，經歷了各種環境壓力，在消除壓力或生活變得更好時，可能會略有改善。這種輕微的改善甚至可能足以使他們不符合抑鬱症的標準。然而，患有嚴重抑鬱症的人可能正在經歷強烈的環境壓力。如果其中一個問題變得更好，它可能會導致某人的生活發生巨大變化。
People with moderate depression, experiencing a variety of environmental stressors, are likely to improve slightly when a stressor is removed, or when their life gets better. This slight improvement may even be enough to move them toward not meeting criteria for depression. People with severe depression, though, are likely experiencing intense environmental stressors. If one of these problems changes for the better, it can make for a dramatic shift in someone’s life.

因此，在這些經歷中處於極端的人在統計上更有可能經歷向平均經歷的更顯著轉變。這些變化是自發發生的，通過一個人生活中所有復雜性的轉變。
Thus, the people on the extremes of these experiences are statistically more likely to undergo a more significant shift toward the average experience. These changes happen spontaneously, through the shifting of all of the complexities of a person’s life.

回歸均值的常用比喻是棒球運動員。在一個偉大的賽季之後（假設他們打了很多本壘打），球迷們希望這名球員在下個賽季也能表現得一樣好。但是，通常情況下，這不會發生。在體育運動中，這被稱為大二低迷(sophomore slump)。發生這種情況是因為這名球員並沒有比其他職業球員好多少——他們只是在那個賽季走運了。很有可能，在整個團隊中，一名球員會比其他球員更幸運。但好運不會永遠存在。下個賽季，該球員恢復到平均水平，而另一名球員獲得了幸運命中。
The usual metaphor for regression to the mean is that of a baseball player. After a great season (let’s say they hit a lot of home runs), fans expect that player to do just as well in the next season. But, often, that doesn’t happen. In sports, this is called the sophomore slump. This occurs because the player was not that much better than the other professional players—they just got lucky that season. Chances are, across a whole team, one player would get a bit more fortunate than the rest. But luck doesn’t hold forever. The next season, that player is back to average, and a different player gets the lucky hits.

大多數精神病藥物有效性研究都招募了症狀相當嚴重的人——這意味著他們的整個參與者池可能都包含這些異常值。
Most psychiatric drug effectiveness studies enroll people with pretty severe symptoms—meaning that their entire participant pool may consist of these outliers.

Hengartner 為患有抑鬱症的退伍軍人提供了重複經顱磁刺激 (rTMS)臨床試驗的真實示例。被選中參加該試驗的參與者已經接受了幾次藥物試驗並且沒有改善，因此他們被認為是“治療抵抗(treatment resistant)”。許多退伍軍人還被診斷出患有創傷後應激障礙(PTSD)、藥物濫用，並被認為有自殺傾向。
Hengartner provides the real example of a clinical trial of repetitive transcranial magnetic stimulation (rTMS) for veterans with depression. The participants selected for this trial had undergone several trials of medication and did not improve, so they were considered “treatment resistant.” Many of the veterans also had diagnoses of PTSD, substance abuse, and were deemed to be suicidal.

由於這些退伍軍人已經經歷了幾次藥物試驗而沒有改善，他們已經體驗到了安慰劑效應的潛力（接受旨在糾正他們症狀的治療）——而且對他們中的任何一個人都不起作用。因此，可以預期本研究中的安慰劑反應率將非常低，接近於零。
Since these veterans had already experienced several trials of medication without improvement, they had already experienced the potential for the placebo effect (receiving treatment intended to remedy their symptoms)—and it had not worked for any of them. Thus, it could be expected that the placebo response rate in this study would be very low, close to zero.

相反，在不到兩週的時間裡，在假rTMS 治療後(fake rTMS treatment)，驚人的 37% 緩解了。實際治療後緩解率略高 41%（請注意，這種差異沒有統計學意義，這意味著實際治療並不比安慰劑好）。也就是說，37% 的人症狀有所緩解，而不僅僅是改善，這意味著他們改善了很多，他們不再患有診斷出的疾病。
Instead, after less than two weeks, an astonishing 37% remitted after fake rTMS treatment. A slightly higher 41% remitted after the real treatment (note that this difference was not statistically significant, meaning that the actual treatment was no better than placebo). That is, 37% had remission of symptoms, not just improvement, meaning they improved so much they no longer had the diagnosed disorder.

現在，這是一個非常高的數字。根據這項研究，37% 的人在嘗試藥物但沒有改善的情況下，可以在不到兩週的時間內治愈抑鬱症、創傷後應激障礙、自殺和藥物濫用。根據 Hengartner 的說法，該研究的研究人員將這種改善歸咎於安慰劑效應——來自醫務人員的關注以及對這種治療有效的信念(the belief that this treatment would work.)。
Now, this is an incredibly high number. According to this study, 37% of people could be cured of depression, PTSD, suicidality, and substance abuse, after having tried drugs with no improvement, all by using a fake treatment, in less than two weeks. The researchers of that study, according to Hengartner, pin that improvement on the placebo effect—attention from medical staff and the belief that this treatment would work.

但他們已經嘗試了兩種本應有效的治療方法，但沒有出現這種改善。為什麼他們會相信這種實驗性的、有爭議的程序會比既定的治療方法效果更好？
But they’d already tried two treatments that were supposed to work, without experiencing that improvement. Why would they believe this experimental, controversial procedure would work better than the established treatments?

Hengartner 提供了另一種可能性。安慰劑效應和實際 rTMS 效應實際上都是由於回歸均值。為這項研究選擇的參與者無疑在用於測試他們的措施的極端得分，有嚴重的自殺性抑鬱症和 PTSD 症狀，以及藥物濫用。因此，根據多年對均值回歸的研究，研究人員應該預料到的統計趨勢是，這些參與者中的許多人本可以在沒有任何治療的情況下自發好轉。
Hengartner provides an alternative possibility. Both the placebo effect and the actual rTMS effect were actually due to regression to the mean. The participants selected for this study were undoubtedly scoring at the extreme ends of the measures used to test them, with severe, suicidal depression and PTSD symptoms, as well as substance abuse. So the statistical trend that researchers should have expected, based on years of research into regression to the mean, is that many of these participants could have gotten better spontaneously, without any treatment at all.

Hengartner 提供了其他研究的證據來支持這一說法。2013 年的一項研究發現，如果不進行治療，53% 的人有望在一年內完全緩解抑鬱症。即使在短期內（3 個月或更短時間），也有 23% 的人在沒有治療的情況下從抑鬱症中得到緩解。
Hengartner provides evidence from other research to back up this claim. A study from 2013 found that, without treatment, 53% of people could expect to experience full remission from depression within a year. Even in the short-term (3 months or less), 23% of people had remission from depression without treatment.

Hengartner 引用的另一項分析發現，無論接受安慰劑治療還是完全不接受治療，抑鬱症完全緩解的人數是相同的——這是回歸均值的明確指標。
Another analysis cited by Hengartner found that the number of people who experienced full remission from depression was the same whether they received placebo treatment or no treatment at all—a clear indicator of regression to the mean.

最後，他將這些數字與STAR*D 試驗進行了比較——這是最大、最全面的抗抑鬱藥物真實世界試驗。在 STAR*D 的短期結果中，28% 的參與者在服用抗抑鬱藥物時出現緩解。
Finally, he compares these numbers to the STAR*D trial—the largest and most comprehensive real-world trial of antidepressant medications. In the short-term results from STAR*D, 28% of the participants experienced remission while taking an antidepressant drug.

這個數字（服用藥物後的 28%）可能與未治療後緩解的 23% 有統計學差異，但不太可能具有臨床意義。並且需要注意的是，從長期來看，STAR*D 試驗證明了藥物的失敗——在一年的隨訪中，仍然參加試驗的參與者中只有約 3% 的抑鬱症得到了緩解. 同時，隨著時間的推移，沒有任何治療會導致越來越多的人得到改善，一年後改善高達 53%。
This number—28% after taking a drug—may be statistically different from the 23% who experienced remission after no treatment, but it is unlikely to be clinically significant. And it should be noted that in the long-term, the STAR*D trial demonstrated the failure of the drugs—only about 3% of the participants that were still enrolled in the experiment had remission of depression at the one-year follow-up. Meanwhile, no treatment at all results in more and more people improving over time, up to 53% by one year.

Hengartner 的分析表明，回歸均值是精神科藥物有效性的很大一部分，長期數據表明完全不治療會產生更好的結果，這對精神科干預的大部分研究基礎提出了質疑。
Hengartner’s analysis suggests that regression to the mean is responsible for a large part of psychiatric drug effectiveness and that long-term data demonstrate better results from no treatment at all, throwing into question much of the research base of psychiatric interventions.

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Hengartner, Michael P. (2019)。在急性抑鬱症治療中是否存在真正的安慰劑效應？重新評估回歸到平均和自發緩解。BMJ 循證醫學。首次在線發布：2019 年 4 月 11 日。doi：10.1136/bmjebm-2019-111161 （鏈接）
Hengartner, Michael P. (2019). Is there a genuine placebo effect in acute depression treatments? A reassessment of regression to the mean and spontaneous remission. BMJ Evidence-Based Medicine. Published Online First: 11 April 2019. doi: 10.1136/bmjebm-2019-111161 (Link)

Peter SimonsPeter Simons was an academic researcher in psychology. Now, as a science writer, he tries to provide the layperson with a view into the sometimes inscrutable world of psychiatric research. As an editor for blogs and personal stories at Mad in America, he prizes the accounts of those with lived experience of the psychiatric system and shares alternatives to the biomedical model.

文章來源:
https://www.madinamerica.com/2019/04/impact-regression-mean-psychiatric-drug-studies/