AIM To determine the placebo response rate associated with different types of placebo interventions used in psychological intervention studies for irritable bowel syndrome. METHODS Randomized controlled trials compari...AIM To determine the placebo response rate associated with different types of placebo interventions used in psychological intervention studies for irritable bowel syndrome. METHODS Randomized controlled trials comparing psychological interventions(stress management/relaxation therapy(cognitive) behavioral therapy, short-term psychodynamic therapy, and hypnotherapy) for the treatment of adult patients with irritable bowel syndrome(IBS) diagnosed with the Manning or Rome criteria with an adequate placebo control treatment and reporting data on IBS symptom severity were identified by searching Pub Med, Embase, the Cochrane Library, CINAHL and Psyc INFO databases. Full-text articles that were written in English and published between 1966 and February 2016 in peer-reviewed journals were selected for the present review. Placebo interventions were considered to be adequate if the number of sessions and the amount of time spent with the therapist were the same as in the active treatment. The placebo response rate(PRR) was computed for IBS symptom severity(primary outcome measure) as well as for anxiety, depression and quality of life(secondary outcome measures). RESULTS Six studies, with a total of 555 patients met the inclusion criteria. Four studies used an educational intervention, whereas two studies used a form of supportive therapy as the placebo intervention. The PRR for IBS symptom severity ranged from 25% to 59%, with a pooled mean of 41.4%. The relative PRR for the secondary outcome measures ranged from 0% to 267% for anxiety, 6% to 52% for depression 20% to 125% for quality of life. The PRR associated with pharmacological treatments, treatment with dietary bran and complementary medicine ranged from 37.5% to 47%. Contrary to our expectations, the PRR in studies on psychological interventions was comparable to that in studies on pharmacological, dietary and alternative medical interventions.CONCLUSION The PRR is probably determined to a larger extent by patient-related factors, such as expectations and desire for the treatment to be effective, than the content of the placebo intervention.展开更多
Objective:The majority of non-small cell lung cancer(NSCLC)cases remain undiagnosed until advanced stages of the disease.Accumulating studies have highlighted the utility of palliative care as an effective treatment o...Objective:The majority of non-small cell lung cancer(NSCLC)cases remain undiagnosed until advanced stages of the disease.Accumulating studies have highlighted the utility of palliative care as an effective treatment option,which relieves patients’suffering by activating placebo effect in the body.To evaluate the clinical significance of palliative care,data from NSCLC drug-randomized controlled trials(RCTs)were collected and the effects of placebo treatment examined.Methods:PubMed(MEDLINE),Scopus,Web of Science,and China National Knowledge Infrastructure databases were searched from January 1,1978 to September 1,2020.Placebo-controlled phase II/III pharmaceutical RCTs enrolling patients with solely stage III/IV NSCLC were included.The quality of included studies was assessed using the Jadad method.Single-arm and two-arm meta-analyses of the therapeutic and adverse effects of placebo,that is,the primary and secondary outcome measures,were subsequently performed using either Bayesian or conventional models.Results:Five RCTs including 2245 drug-treated and 1510 placebo-treated patients at NSCLC stage III or IV were included for the study.Low risk of bias was observed for all five included studies using the Cochrane method.Following placebo treatment,controlled disease rate of 24.1%(95%credible interval[CrI],-0.126-0.609)and dropout rate of 2.1%(95%CrI,0.007-0.039)were calculated,with a dose reduction rate of 3.0%(95%CrI,0.017-0.045).Compared with active drug treatment,the placebo treatment group had a risk ratio of 0.81(95%confidence interval,0.68-0.97)and 0.85(95%confidence interval,0.76-0.96)for the achievement of progression-free survival and overall survival,respectively.Conclusion:In NSCLC drug RCTs,placebo treatment is indicated to generally induce low toxicity in patients by dropout and dose reduction rates and adverse events,although the therapeutic responses could not be precisely determined.The results suggest that under specific circumstances,palliative care which can activate placebo effect may have similar effects as active drugs(such as erlotinib,vandetanib,or pemetrexed)in terms of prolonging survival time.展开更多
Abstract The placebo effect is a very powerful and unpredictable aspect of any medical treatment. Assuch, it dramatically complicates efforts at convincingly demonstrating the effectiveness of specitic effects inmedic...Abstract The placebo effect is a very powerful and unpredictable aspect of any medical treatment. Assuch, it dramatically complicates efforts at convincingly demonstrating the effectiveness of specitic effects inmedicine, conventional or alternative. This review provides a tlieoretical overview of tlie placebo effect toassist researchers in designing trials, controlled or otliereise, so that more convincing demoiistrations of spe-cific effects can be achieved.展开更多
In clinical trials, drug effect is measured by a difference between subjects who are treated by experimental drug against placebo-treated subjects. In case of binary data, with observing YES/NO on each subject in cert...In clinical trials, drug effect is measured by a difference between subjects who are treated by experimental drug against placebo-treated subjects. In case of binary data, with observing YES/NO on each subject in certain period of time, it is the proportion of subjects who respond in treatment group minus the proportion of responders in placebo group (for example, 50% vs. 30%). However, a greater difference was proposed by Rihmer et al. (2011) [1] with their supporting arguments, in that antidepressant response and placebo response had different mechanisms and there were equal chances for antidepressant responder to be responding to placebo and not responding to placebo at all. Therefore, the authors proposed 50% - 30% * 50% when the response rate in the treatment group and the placebo group are 50% and 30% respectively, resulting in higher drug-placebo difference than traditional understanding of 50% - 30%. In this article, we tried to explain why the authors misunderstood the drug-placebo concept for evaluating drug superiority, their misunderstanding of assumptions of traditional calculation, as well as their wrong reasoning on their proposed approach. All in all, we conclude the traditional approach of 50% - 30% is the right way of evaluating drug-placebo difference and the possible methods to control impact of placebo effect are briefly discussed at the end of this article.展开更多
The hypothesis in drug clinical trials is that the drug is better than a placebo in patients suffering from a disease. The unstated assumption is that the drug cures the disease or is a powerful treatment for the dise...The hypothesis in drug clinical trials is that the drug is better than a placebo in patients suffering from a disease. The unstated assumption is that the drug cures the disease or is a powerful treatment for the disease. This is an incorrect assumption. Drugs do not cure or treat diseases. The body heals itself; drugs promote this ability of the body to heal itself. Placebos are assumed to be inactive; however, placebos can also promote the ability of the body to heal itself. Placebos are actually treatments that can stimulate endogenous healing mechanisms. The possible place of placebos in health management is controversial. Clinical trial design should be altered. The hypothesis of clinical trials should be that the drug speeds up or improves the healing of the patient, putting patient healing as the first objective. Placebos should not be used as controls but could be tested as drugs in their own right. The control in clinical trials should be no treatment. Alternatively, new drugs could be compared to existing drugs in clinical trials.展开更多
为考察安慰剂效应在情绪调节中的脑机制,本研究以社会排斥图片为情绪诱发材料诱发社会疼痛,采用经颅磁刺激技术(transcranial magnetic stimulation,TMS)激活背外侧前额叶(dorsolateral prefrontal cortex,DLPFC),并使用事件相关电位观...为考察安慰剂效应在情绪调节中的脑机制,本研究以社会排斥图片为情绪诱发材料诱发社会疼痛,采用经颅磁刺激技术(transcranial magnetic stimulation,TMS)激活背外侧前额叶(dorsolateral prefrontal cortex,DLPFC),并使用事件相关电位观测TMS对安慰剂下调社会疼痛的影响。实验以“TMS组别”(DLPFC组、控制组)为被试间变量,“安慰剂条件”(安慰剂、非安慰剂)为被试内因素。结果发现,DLPFC组(n=50)比控制组(n=50)在安慰剂条件下报告的负性情绪更弱,反映情绪体验强度的晚正成分的波幅也更低,上述组间差异在非安慰剂条件不显著。结果还表明,DLPFC组比控制组更相信安慰剂的效果,愿意花更多的钱来购买安慰剂。此外相关结果发现,由DLPFC激活导致的安慰剂效应增强可有效降低社交焦虑倾向被试的负性社会情绪。本研究是结合脑调控和脑观测技术探讨安慰剂情绪调节脑机制的首次尝试,研究发现不但揭示了DLPFC在安慰剂调节情绪过程中的重要因果作用,还为临床治疗以情绪失调为主要症状的抑郁焦虑等精神障碍患者提供了脑调控干预的可行性脑靶点。展开更多
目的系统评价中药在失眠治疗中的安慰剂效应(Effects Associated With Placebo,EAP)。方法全面检索计算机检索中国生物医学文献数据库(CBM-disc,1978年1月~2015年12月)、中国期刊全文数据库(CNKI,1979年1月~2015年12月)、中文科技期刊...目的系统评价中药在失眠治疗中的安慰剂效应(Effects Associated With Placebo,EAP)。方法全面检索计算机检索中国生物医学文献数据库(CBM-disc,1978年1月~2015年12月)、中国期刊全文数据库(CNKI,1979年1月~2015年12月)、中文科技期刊全文数据库(VIP,1989年1月~2015年12月)、万方数据库(1978年1月~2015年12月)等。全面收集中药和安慰剂治疗失眠的随机对照实验,同时手工检索及追溯参考文献,由二位研究者根据纳入与排除标准独立筛选文献,提取资料和评价纳入研究的方法学质量后,采用Rev Man 5.3软件进行Meta分析。结果最终纳入18个RCT,共计1913例患者,分别采用有效率和匹兹堡睡眠质量指数(Pittsburgh Sleep quality Index,PSQI)评分进行评价。Meta分析显示:失眠治疗前后有效率:亚组1有效率为60.3%,合并OR值为7.14,95%可信区间CI[4.99,10.21,P<0.00001];亚组2有效率为39.7%,合并OR值为9.64,95%可信区间CI[6.47,14.37,P<0.00001];PSQI评分比较睡眠潜伏期(Sleep Latency,SL)、睡眠总时间(Total Sleep Time,TST)、多导睡眠图(Polysomnographic,PSG)SL安慰剂治疗前后的变化,其差异均有统计学意义。结论未来对于中医药治疗失眠的临床试验中应保留安慰剂治疗,并进一步规范中药安慰剂的制作。展开更多
文摘AIM To determine the placebo response rate associated with different types of placebo interventions used in psychological intervention studies for irritable bowel syndrome. METHODS Randomized controlled trials comparing psychological interventions(stress management/relaxation therapy(cognitive) behavioral therapy, short-term psychodynamic therapy, and hypnotherapy) for the treatment of adult patients with irritable bowel syndrome(IBS) diagnosed with the Manning or Rome criteria with an adequate placebo control treatment and reporting data on IBS symptom severity were identified by searching Pub Med, Embase, the Cochrane Library, CINAHL and Psyc INFO databases. Full-text articles that were written in English and published between 1966 and February 2016 in peer-reviewed journals were selected for the present review. Placebo interventions were considered to be adequate if the number of sessions and the amount of time spent with the therapist were the same as in the active treatment. The placebo response rate(PRR) was computed for IBS symptom severity(primary outcome measure) as well as for anxiety, depression and quality of life(secondary outcome measures). RESULTS Six studies, with a total of 555 patients met the inclusion criteria. Four studies used an educational intervention, whereas two studies used a form of supportive therapy as the placebo intervention. The PRR for IBS symptom severity ranged from 25% to 59%, with a pooled mean of 41.4%. The relative PRR for the secondary outcome measures ranged from 0% to 267% for anxiety, 6% to 52% for depression 20% to 125% for quality of life. The PRR associated with pharmacological treatments, treatment with dietary bran and complementary medicine ranged from 37.5% to 47%. Contrary to our expectations, the PRR in studies on psychological interventions was comparable to that in studies on pharmacological, dietary and alternative medical interventions.CONCLUSION The PRR is probably determined to a larger extent by patient-related factors, such as expectations and desire for the treatment to be effective, than the content of the placebo intervention.
基金Natural Science Foundation of Shanghai(No.19ZR1427700)Ministry of Science and Technology of China(No.2017YFC1001302)Shanghai Key Laboratory of Psychotic Disorders(13dz2260500)in Shanghai Mental Health Center,China(No.19-K02).
文摘Objective:The majority of non-small cell lung cancer(NSCLC)cases remain undiagnosed until advanced stages of the disease.Accumulating studies have highlighted the utility of palliative care as an effective treatment option,which relieves patients’suffering by activating placebo effect in the body.To evaluate the clinical significance of palliative care,data from NSCLC drug-randomized controlled trials(RCTs)were collected and the effects of placebo treatment examined.Methods:PubMed(MEDLINE),Scopus,Web of Science,and China National Knowledge Infrastructure databases were searched from January 1,1978 to September 1,2020.Placebo-controlled phase II/III pharmaceutical RCTs enrolling patients with solely stage III/IV NSCLC were included.The quality of included studies was assessed using the Jadad method.Single-arm and two-arm meta-analyses of the therapeutic and adverse effects of placebo,that is,the primary and secondary outcome measures,were subsequently performed using either Bayesian or conventional models.Results:Five RCTs including 2245 drug-treated and 1510 placebo-treated patients at NSCLC stage III or IV were included for the study.Low risk of bias was observed for all five included studies using the Cochrane method.Following placebo treatment,controlled disease rate of 24.1%(95%credible interval[CrI],-0.126-0.609)and dropout rate of 2.1%(95%CrI,0.007-0.039)were calculated,with a dose reduction rate of 3.0%(95%CrI,0.017-0.045).Compared with active drug treatment,the placebo treatment group had a risk ratio of 0.81(95%confidence interval,0.68-0.97)and 0.85(95%confidence interval,0.76-0.96)for the achievement of progression-free survival and overall survival,respectively.Conclusion:In NSCLC drug RCTs,placebo treatment is indicated to generally induce low toxicity in patients by dropout and dose reduction rates and adverse events,although the therapeutic responses could not be precisely determined.The results suggest that under specific circumstances,palliative care which can activate placebo effect may have similar effects as active drugs(such as erlotinib,vandetanib,or pemetrexed)in terms of prolonging survival time.
文摘Abstract The placebo effect is a very powerful and unpredictable aspect of any medical treatment. Assuch, it dramatically complicates efforts at convincingly demonstrating the effectiveness of specitic effects inmedicine, conventional or alternative. This review provides a tlieoretical overview of tlie placebo effect toassist researchers in designing trials, controlled or otliereise, so that more convincing demoiistrations of spe-cific effects can be achieved.
文摘In clinical trials, drug effect is measured by a difference between subjects who are treated by experimental drug against placebo-treated subjects. In case of binary data, with observing YES/NO on each subject in certain period of time, it is the proportion of subjects who respond in treatment group minus the proportion of responders in placebo group (for example, 50% vs. 30%). However, a greater difference was proposed by Rihmer et al. (2011) [1] with their supporting arguments, in that antidepressant response and placebo response had different mechanisms and there were equal chances for antidepressant responder to be responding to placebo and not responding to placebo at all. Therefore, the authors proposed 50% - 30% * 50% when the response rate in the treatment group and the placebo group are 50% and 30% respectively, resulting in higher drug-placebo difference than traditional understanding of 50% - 30%. In this article, we tried to explain why the authors misunderstood the drug-placebo concept for evaluating drug superiority, their misunderstanding of assumptions of traditional calculation, as well as their wrong reasoning on their proposed approach. All in all, we conclude the traditional approach of 50% - 30% is the right way of evaluating drug-placebo difference and the possible methods to control impact of placebo effect are briefly discussed at the end of this article.
文摘The hypothesis in drug clinical trials is that the drug is better than a placebo in patients suffering from a disease. The unstated assumption is that the drug cures the disease or is a powerful treatment for the disease. This is an incorrect assumption. Drugs do not cure or treat diseases. The body heals itself; drugs promote this ability of the body to heal itself. Placebos are assumed to be inactive; however, placebos can also promote the ability of the body to heal itself. Placebos are actually treatments that can stimulate endogenous healing mechanisms. The possible place of placebos in health management is controversial. Clinical trial design should be altered. The hypothesis of clinical trials should be that the drug speeds up or improves the healing of the patient, putting patient healing as the first objective. Placebos should not be used as controls but could be tested as drugs in their own right. The control in clinical trials should be no treatment. Alternatively, new drugs could be compared to existing drugs in clinical trials.
文摘为考察安慰剂效应在情绪调节中的脑机制,本研究以社会排斥图片为情绪诱发材料诱发社会疼痛,采用经颅磁刺激技术(transcranial magnetic stimulation,TMS)激活背外侧前额叶(dorsolateral prefrontal cortex,DLPFC),并使用事件相关电位观测TMS对安慰剂下调社会疼痛的影响。实验以“TMS组别”(DLPFC组、控制组)为被试间变量,“安慰剂条件”(安慰剂、非安慰剂)为被试内因素。结果发现,DLPFC组(n=50)比控制组(n=50)在安慰剂条件下报告的负性情绪更弱,反映情绪体验强度的晚正成分的波幅也更低,上述组间差异在非安慰剂条件不显著。结果还表明,DLPFC组比控制组更相信安慰剂的效果,愿意花更多的钱来购买安慰剂。此外相关结果发现,由DLPFC激活导致的安慰剂效应增强可有效降低社交焦虑倾向被试的负性社会情绪。本研究是结合脑调控和脑观测技术探讨安慰剂情绪调节脑机制的首次尝试,研究发现不但揭示了DLPFC在安慰剂调节情绪过程中的重要因果作用,还为临床治疗以情绪失调为主要症状的抑郁焦虑等精神障碍患者提供了脑调控干预的可行性脑靶点。
