We sincerely thank the authors of the commentary1 for their thoughtful analysis and constructive critique of our systematic review on ischemic preconditioning(IPC)and placebo effects in exercise capacity and athletic ...We sincerely thank the authors of the commentary1 for their thoughtful analysis and constructive critique of our systematic review on ischemic preconditioning(IPC)and placebo effects in exercise capacity and athletic performance.2Their attention to methodological details,particularly concerning the inclusion and timing of warm-up protocols across studies,is commendable and contributes meaningfully to the ongoing refinement of IPC research in sports science.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
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 comparin...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
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
This study examined the application of the Rumsfeld Matrix to acupuncture clinical trials,particularly those published in leading medical journals such as The Journal of the American Medical Association(JAMA),British ...This study examined the application of the Rumsfeld Matrix to acupuncture clinical trials,particularly those published in leading medical journals such as The Journal of the American Medical Association(JAMA),British Medical Journal(BMJ),The Lancet,and The New Eng-land Journal of Medicine(NEJM).The integration of randomized clinical trials(RCTs)has in-troduced a level of academic rigor to acupuncture research,challenging the classical deter-ministic model and revealing a complex landscape of known knowns,known unknowns,un-known knowns,and unknown unknowns.While RCTs have validated acupuncture’s efficacy in certain conditions,they have also highlighted considerable challenges,including the limi-tations of control group designs and the potential influence of placebo effects.The recurring issue of no significant differences between real and sham acupuncture in many studies un-derscores the need for refined control strategies and a more nuanced understanding of acupuncture’s mechanisms.This investigation calls for continued rigorous research to fully explore acupuncture’s therapeutic potential and its integration into evidence-based medicine,ultimately contributing to improved patient care and broader acceptance within the medical community.展开更多
The primary aim of clinical trials is to investigate whether a treatment is effective for a particular disease or condition. Randomized controlled clinical trials are considered to be the gold standard for evaluating ...The primary aim of clinical trials is to investigate whether a treatment is effective for a particular disease or condition. Randomized controlled clinical trials are considered to be the gold standard for evaluating the effect of a certain intervention. However, in clinical trials, even after randomization, there are situations where the patients differ substantially with respect to the baseline value of the outcome variable. Many a times the response to interventions depends on the baseline values of the outcome variable. When there are baseline-dependent treatment effects, differences among treatments vary as a function of baseline level. Although variation in outcome associated with baseline value is accounted for in ANCOVA, analysis of individual differences in treatment effect is precluded by the homogeneity of regression assumption. This assumption requires that expected differences in outcome among treatments be constant across all baseline levels. To overcome this difficulty, Weigel and Narvaez [7] proposed a regression model for two treatment groups to analyze individual response to treatments in randomized controlled clinical trials. The authors reviewed the model suggested by Weigel and Narvaez and extended further for three or more treatment groups. The utility of the model was demonstrated with real life data from a randomized controlled clinical trial of bronchial asthma.展开更多
The innovative doubly randomized delayed start(DRDS)design has been implemented to tackle the well-known challenge of a high placebo response rate in clinical trials.This design begins with a conventional parallel des...The innovative doubly randomized delayed start(DRDS)design has been implemented to tackle the well-known challenge of a high placebo response rate in clinical trials.This design begins with a conventional parallel design phase(period 1),followed by a subsequent phase(period 2)where subjects initially assigned to placebo and who did not respond are re-randomized to either the test drug or placebo.Chi,G.Y.,Li,Y.,Liu,Y.,Lewin,D.,&Lim,P.(2016 On clinical trials with a high placebo response rate.Contemporary Clinical Trials Communications,2,34-53.https:/doi.org/10.1016/j.conctc.2015.10.002)introduced a new statistical methodology with a conditional probability structure to account for the specific characteristics of the DRDS design.However,some critical formulas in Chi et al.(2016,p.38)for this probability structure are incorrect.Here,we correct these formulas and provide a comprehensive technical background on deriving the probability structurefor a DRDS design to support these corrections.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
Objective： Different kinds of sham acupuncture are widely applied in randomized controlled trials （RCTs） to explore whether acupuncture has intrinsic therapeutic effects beyond the placebo effects for certain indic...Objective： Different kinds of sham acupuncture are widely applied in randomized controlled trials （RCTs） to explore whether acupuncture has intrinsic therapeutic effects beyond the placebo effects for certain indication. To make conclusions of trials more comparable and convincing, it is of great necessity to unify the sham acupuncture procedure. Methods： RCTs of acupuncture with high quality in the recent 14 years were reviewed, and the appropriateness of the sham acupuncture procedures was assessed. Results： The sham acupuncture procedures were mainly classified into five kinds according to their administered sites, penetrating, and intervention apparatus. Conclusion： Among the sham acupuncture procedures, needling near the selected acupoints, needling at a distant non-acupoints, and non-penetrating sham acupuncture are most commonly used. Sham acupuncture performed at distant site belongs to non-meridian and non-acupoint may be an ideal control for the study of the intrinsic therapeutic effects of acupuncture. Besides, the selection of controls must focus on the design and aim of RCTs, such as non-inferiority, equivalence and superiority trials.展开更多
The aim of this article was to assess the clinical evidence for or against the blinding effect of non-penetrating sham needle as placebo needle. This systematic review included randomized controlled trials(RCTs) of ac...The aim of this article was to assess the clinical evidence for or against the blinding effect of non-penetrating sham needle as placebo needle. This systematic review included randomized controlled trials(RCTs) of acupuncture taking non-penetrating sham acupuncture as placebo needle. Systematic searches were conducted in 13 electronic databases up to July 2012: Medline, PubMed, the Cochrane Library, CINAHL, EMBASE, a Chinese medical database. All parallel or cross-over RCTs of acupuncture for the blinding effect of non-penetrating needle were chosen without language restrictions. Finally, totally 7 RCTs met the inclusion criteria. In conclusion, our systematic review and meta-analysis demonstrate that the non-penetrating needle is an effective instrument for placebo control in the acupuncture RCTs.展开更多
文摘We sincerely thank the authors of the commentary1 for their thoughtful analysis and constructive critique of our systematic review on ischemic preconditioning(IPC)and placebo effects in exercise capacity and athletic performance.2Their attention to methodological details,particularly concerning the inclusion and timing of warm-up protocols across studies,is commendable and contributes meaningfully to the ongoing refinement of IPC research in sports science.
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.
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This study examined the application of the Rumsfeld Matrix to acupuncture clinical trials,particularly those published in leading medical journals such as The Journal of the American Medical Association(JAMA),British Medical Journal(BMJ),The Lancet,and The New Eng-land Journal of Medicine(NEJM).The integration of randomized clinical trials(RCTs)has in-troduced a level of academic rigor to acupuncture research,challenging the classical deter-ministic model and revealing a complex landscape of known knowns,known unknowns,un-known knowns,and unknown unknowns.While RCTs have validated acupuncture’s efficacy in certain conditions,they have also highlighted considerable challenges,including the limi-tations of control group designs and the potential influence of placebo effects.The recurring issue of no significant differences between real and sham acupuncture in many studies un-derscores the need for refined control strategies and a more nuanced understanding of acupuncture’s mechanisms.This investigation calls for continued rigorous research to fully explore acupuncture’s therapeutic potential and its integration into evidence-based medicine,ultimately contributing to improved patient care and broader acceptance within the medical community.
文摘The primary aim of clinical trials is to investigate whether a treatment is effective for a particular disease or condition. Randomized controlled clinical trials are considered to be the gold standard for evaluating the effect of a certain intervention. However, in clinical trials, even after randomization, there are situations where the patients differ substantially with respect to the baseline value of the outcome variable. Many a times the response to interventions depends on the baseline values of the outcome variable. When there are baseline-dependent treatment effects, differences among treatments vary as a function of baseline level. Although variation in outcome associated with baseline value is accounted for in ANCOVA, analysis of individual differences in treatment effect is precluded by the homogeneity of regression assumption. This assumption requires that expected differences in outcome among treatments be constant across all baseline levels. To overcome this difficulty, Weigel and Narvaez [7] proposed a regression model for two treatment groups to analyze individual response to treatments in randomized controlled clinical trials. The authors reviewed the model suggested by Weigel and Narvaez and extended further for three or more treatment groups. The utility of the model was demonstrated with real life data from a randomized controlled clinical trial of bronchial asthma.
文摘The innovative doubly randomized delayed start(DRDS)design has been implemented to tackle the well-known challenge of a high placebo response rate in clinical trials.This design begins with a conventional parallel design phase(period 1),followed by a subsequent phase(period 2)where subjects initially assigned to placebo and who did not respond are re-randomized to either the test drug or placebo.Chi,G.Y.,Li,Y.,Liu,Y.,Lewin,D.,&Lim,P.(2016 On clinical trials with a high placebo response rate.Contemporary Clinical Trials Communications,2,34-53.https:/doi.org/10.1016/j.conctc.2015.10.002)introduced a new statistical methodology with a conditional probability structure to account for the specific characteristics of the DRDS design.However,some critical formulas in Chi et al.(2016,p.38)for this probability structure are incorrect.Here,we correct these formulas and provide a comprehensive technical background on deriving the probability structurefor a DRDS design to support these corrections.
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.
基金National Natural Science Foundation of China (No. 30873299, 90409014, 81001548, 30701123)Shanghai Leading Academic Discipline Project (S30304)
文摘Objective： Different kinds of sham acupuncture are widely applied in randomized controlled trials （RCTs） to explore whether acupuncture has intrinsic therapeutic effects beyond the placebo effects for certain indication. To make conclusions of trials more comparable and convincing, it is of great necessity to unify the sham acupuncture procedure. Methods： RCTs of acupuncture with high quality in the recent 14 years were reviewed, and the appropriateness of the sham acupuncture procedures was assessed. Results： The sham acupuncture procedures were mainly classified into five kinds according to their administered sites, penetrating, and intervention apparatus. Conclusion： Among the sham acupuncture procedures, needling near the selected acupoints, needling at a distant non-acupoints, and non-penetrating sham acupuncture are most commonly used. Sham acupuncture performed at distant site belongs to non-meridian and non-acupoint may be an ideal control for the study of the intrinsic therapeutic effects of acupuncture. Besides, the selection of controls must focus on the design and aim of RCTs, such as non-inferiority, equivalence and superiority trials.
基金supported by Traditional Chinese Medicine and Integrated Traditional and Western Medicine Scientific Research Project of Tianjin Municipal Administration of Traditional Chinese Medicine(No.11047)Development Plan of Changjiang Scholars and Innovative Research Team
文摘The aim of this article was to assess the clinical evidence for or against the blinding effect of non-penetrating sham needle as placebo needle. This systematic review included randomized controlled trials(RCTs) of acupuncture taking non-penetrating sham acupuncture as placebo needle. Systematic searches were conducted in 13 electronic databases up to July 2012: Medline, PubMed, the Cochrane Library, CINAHL, EMBASE, a Chinese medical database. All parallel or cross-over RCTs of acupuncture for the blinding effect of non-penetrating needle were chosen without language restrictions. Finally, totally 7 RCTs met the inclusion criteria. In conclusion, our systematic review and meta-analysis demonstrate that the non-penetrating needle is an effective instrument for placebo control in the acupuncture RCTs.
