***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This study examined the accuracy of insomnia patients and their treating physicians in rating whether an active hypnotic drug or a placebo was given in treatment . Forty older adults with primary insomnia were r and omly assigned to either an active ( temazepam ) or a placebo condition using a double-blind strategy . Ratings of treatment conditions were obtained at 1 week ( early treatment ) , 4 weeks ( midtreatment ) , and 8 weeks ( late treatment ) . Patients were able to accurately discriminate ( beyond chance levels ) between the active and placebo medications at the early ( 76.9 % accuracy ) and late treatment assessment timepoints ( 78.1 % accuracy ) , but not at midtreatment ( 51.5 % accuracy ) . Therapists , however , were able to make accurate discriminations at the late treatment assessment timepoint only ( 80 % accuracy ) ; early ( 69.2 % accuracy ) and midtreatment ( 47.2 % accuracy ) ratings did not exceed chance levels . Patients who had used hypnotic drugs prior to this trial were more accurate in their judgments of treatment conditions than those without prior exposure . The findings raise an important issue about the internal validity of the double-blind strategy , which may in fact be only a single-blind procedure & NA ; Patient , provider , and clinical investigator expectations concerning treatments are believed to play important roles in patient response . This study examined the association of patient and research nurse/physician pretreatment expectations of pain relief with actual pain relief , the accuracy of patient and research nurse guesses about patient medication assignment , and changes in research nurse and patient pain relief expectations over the course of a r and omized double‐blind trial of amitriptyline versus an active placebo for patients with chronic pain and spinal cord injuries ( SCI ) . Patient expectations of pain relief with amitriptyline were associated significantly with actual pain decrease for patients in the  amitriptyline  , but not placebo , condition . Research nurse/physician expectations did not predict patient pain relief . Both patients and the research nurse were able to guess patient medication assignment at a rate significantly greater than chance . The research nurse 's , but not the patients ’ , expectations of pain relief with amitriptyline decreased significantly over the course of the study . These findings have implication s for future r and omized controlled trials . Fully double‐blind conditions are very difficult to achieve , and it is informative to assess patient and research clinician expectations and guesses regarding medication assignment Background : In r and omised controlled trials , an increasingly used test of the ‘ blindness ’ of assessors is to have them guess the group to which each participant has been allocated . Because assessors are usually aware of the trial hypotheses , we predicted that trial participants who showed the greatest improvement would be assumed by an assessor to have been in the ‘ preferred intervention ’ group . Methods : Data were derived from a trial in recent-onset rheumatoid arthritis comparing cognitive behavioural therapy plus routine care with routine care alone . Results : Although in this trial assessor blindness was demonstrated , patients ‘ guessed ’ by the assessor to be in the cognitive therapy group showed significantly greater improvements than those predicted to have received routine care alone in variables predicted to change in the study protocol . Conclusions : These results indicate that even if an assessor ’s guesses about patient group allocations are more accurate than expected by chance , this would not necessarily demonstrate failure of blinding . This casts further doubt on the validity of forced choice paradigms in testing the integrity of blinding in clinical trials & NA ; Individual differences in pharmacokinetics and pharmacodynamics , the type of pain and the method of drug administration can account for the response variability to analgesics . By integrating a clinical and an experimental approach , we report here that another important source of variability is represented by individual differences in non‐specific ( placebo ) activation of endogenous opioid systems . In the first part of this study , we analyzed the effectiveness of buprenorphine , tramadol , ketorolac and metamizol in the clinical setting , where the placebo effect was completely eliminated by means of hidden infusions . We found that the hidden injections were significantly less effective and less variable compared with open injections ( in full view of the subject ) , suggesting that part of the response variability was due to non‐specific factors ( placebo ) . Since we could not administer the opioid antagonist , naloxone , to these patients , in the second part of this study , we induced experimental ischemic arm pain in healthy volunteers and found that , as occurred in clinical pain , the analgesic response to a hidden injection of the non‐opioid ketorolac was less effective and less variable than an open injection . Most importantly , we obtained the same effects by adding naloxone to an open injection of ketorolac , thus blocking the opioid‐mediated placebo component of analgesia . These findings indicate that both the psychological ( hidden injection ) and pharmacological ( naloxone ) blockade of the placebo response reduce the effectiveness of , and the response variability to , analgesic drugs . Therefore , an important source of response variability to analgesics appears to be due to differences in non‐specific activation of endogenous opioid systems In this report , the authors explore the relationships of perceived treatment to outcome in a large , placebo-controlled trial of  nicotine replacement treatment for smoking reduction .  In the original study ( J. F. Etter , E. Laszlo , J. P. Zellweger , C. Perrot , & T. V. Perneger , 2002 ) , which was conducted in French-speaking Switzerl and , smokers were r and omly assigned to receive nicotine , matching placebo products , or no intervention . At the end of the 6-month study , participants were asked to guess whether they had received nicotine or placebo . In the present analysis , the authors examined the difference in smoking reduction between those who believed they had received nicotine and those who believed they had received placebo . Regardless of actual treatment , smokers who believed they had received nicotine had significantly better outcome than those who believed they had received placebo CONTEXT This study was part of a large double-blind sham surgery-controlled trial design ed to determine the effectiveness of transplantation of human embryonic dopamine neurons into the brains of persons with advanced Parkinson 's disease . This portion of the study investigated the quality of life ( QOL ) of participants during the 1 year of double-blind follow-up . OBJECTIVES To determine whether QOL improved more in the transplant group than in the sham surgery group and to investigate outcomes at 1 year based on perceived treatment ( the type of surgery patients thought they received ) . DESIGN Participants were r and omly assigned to receive either the transplant or sham surgery . Reported results are from the 1-year double-blind period . SETTING Participants were recruited from across the United States and Canada . Assessment and surgery were conducted at 2 separate university medical centers . PARTICIPANTS A volunteer sample of 40 persons with idiopathic Parkinson 's disease participated in the transplant ( " parent " ) study , and 30 agreed to participate in the related QOL study : 12 received the transplant and 18 received sham surgery . INTERVENTIONS Interventions in the parent study were transplantation and sham brain surgery . Assessment s of QOL were made at baseline and 4 , 8 , and 12 months after surgery . MAIN OUTCOME MEASURES Comparison of the actual transplant and sham surgery groups and the perceived treatment groups on QOL and medical outcomes . We also investigated change over time . RESULTS There were 2 differences or changes over time in the transplant and sham surgery groups . Based on perceived treatment , or treatment patients thought they received , there were numerous differences and changes over time . In all cases , those who thought they received the transplant reported better scores . Blind ratings by medical staff showed similar results . CONCLUSIONS The placebo effect was very strong in this study , demonstrating the value of placebo-controlled surgical trials BACKGROUND Blinding can reduce bias in r and omized clinical trials , but blinding procedures may be unsuccessful . Our aim was to assess how often r and omized clinical trials test the success of blinding  , the methods involved and how often blinding is reported as being successful . METHODS We analysed a r and om sample of blinded r and omized clinical trials indexed in the The Cochrane Central Register of Controlled Trials and published in 2001 . We identified 1599 blinded trials , and noted if they had conducted any test for the success of blinding . We also selected 200 trials r and omly that did not report any such test , and sent a question naire to the corresponding authors asking them if they had conducted any tests . RESULTS Thirty-one out of 1599 trials ( 2 % ) reported tests for the success of blinding . Test methods varied , and reporting was generally incomplete . Blinding was considered successful in 14 out of the 31 trials ( 45 % ) and unclear in 10 ( 32 % ) . Of the seven trials ( 23 % ) reporting unsuccessful blinding the risk of a biased trial result was either not addressed or was discounted in six cases . We received 130 question naires from trial authors ( 65 % ) of which 15 ( 12 % ) informed that they had conducted , but not published , tests . CONCLUSIONS Blinding is rarely tested . Test methods vary , and the reporting of tests , and test results , is incomplete . There is a considerable method ological uncertainty how best to assess blinding , and an urgent need for improved methodology and improved reporting Psychopharmacological studies usually attempt to eliminate " nonspecific " influences on outcome by double-blind design s. In a r and omized , double-blind comparison of alprazolam , imipramine , and placebo , the great majority of panic disorder patients ( N = 59 ) and their physicians were able to rate accurately whether active drug or placebo had been given . Moreover , physicians could distinguish between the two types of active drugs . Inasmuch as correct rating was possible halfway through treatment , concerns about the internal validity of the double-blind strategy arise This purpose of this article is to contrast the analgesic efficacy of acupuncture following dental surgery with the analgesic effects based on the expectation of benefit in two independently conducted placebo-controlled trials evaluating acupuncture as an adjunctive therapy for dental surgery . Both trials used pain following dental surgery as the outcome variable , and both included a blinding check to ascertain patients ’ beliefs regarding which treatment they were receiving . Although no statistically significant analgesic effect was observed between the acupuncture and placebo groups , participants in both experiments who believed they received real acupuncture  reported significantly less pain than patients who believed that they received a placebo . Patients ’ beliefs regarding the receipt of acupuncture bore a stronger relationship to pain than any specific action possessed by acupuncture . These results also support the importance of both employing credible controls for the placebo effect in clinical trials and evaluating the credibility of those controls Heading Abstract Rationale . Critics have called into question findings from double-blind placebo-controlled studies because subjects are given drug administration instructions informing them of a placebo condition . The assertion that these drug administration instructions bias estimates of effectiveness has undergone surprisingly little empirical investigation . Objectives . The primary objective of this study was to determine whether drug administration instructions informing subjects of a placebo condition affect the drug response and affect the saliva concentration of the stimulant . Methods . We assessed  caffeine responses and levels of saliva concentration of caffeine in 52 subjects who were r and omly assigned to receive one of two drug administration instructions : ( a ) placebo-informed instructions ( i.e. , individuals informed of the placebo ) analogous to those used in double-blind studies and ( b ) placebo-uninformed instructions ( i.e. , individuals informed they are taking an active stimulant ) . Results . On most measures ( systolic blood pressure , heart rate , h and steadiness , reaction time , fatigue , and tension ) , drug administration instructions did not significantly influence caffeine response . Instructions also had no significant effect on saliva concentration of caffeine . However , only individuals who were uninformed of the placebo condition showed significant diastolic blood pressure and vigor increases with 125 mg caffeine , and significant h and steadiness impairment and vigor increases with 325 mg caffeine compared to placebo . Conclusions . These overall findings suggest that a limited bias is introduced by drug administration instructions . The results do not support any suggestion that information about the existence of a placebo condition dramatically influences conclusions drawn about drug responses in placebo-controlled trials The objective of this study was to assess whether nicotine replacement therapy , administered in a real-life situation , could reduce cigarette consumption in smokers who were not prepared to quit smoking . Daily smokers of more than 20 cigarettes per day who had no intention to quit smoking in the next 6 months were recruited from the general population and r and omly assigned to either a 6-month treatment of nicotine ( choice among a 15-mg nicotine patch , a 4-mg nicotine gum , a 10-mg nicotine inhaler , or a combination of these , N = 265 ) , matching placebo products ( N = 269 ) , or no intervention ( N = 389 ) . Products were sent to participants by mail . Education was limited to a booklet . Of 923 participants , 879 ( 95 % ) were followed up after 6 months . Mean baseline consumption was 30 cigarettes per day in all groups . At 6 months , cigarette consumption decreased by a median of 10 cigarettes per day in the nicotine group , 7.5 in the placebo group , and 2.5 among controls ( p < 0.04 for all pair-wise comparisons ) . Smoking cessation rates were low ( 2%–4 % ) and did not differ significantly between groups . Quit attempts were less frequent among controls ( 21 % ) than among the nicotine ( 28 % , p = 0.04 ) and placebo ( 27 % , p = 0.08 ) subjects . In conclusion , nicotine replacement therapy helped smokers reduce their cigarette consumption and maintain this reduction over 6 months , but a large part of this reduction was attributable to a placebo effect 
    Output:
    
First , when blinding fails research es can not determine whether any observed improvement in the group receiving active treatment result ed because of the treatment ’s effect or because of participants ’ expectancies .
Second , participant expectancies could create ceiling effects if there are strong placebo effects in each treatment arm and this may falsely suggest that the active treatment is ineffective without expectancy .
Third , the knowledge that a participant will be allocated active treatment or placebo in double-blind placebo-controlled RCTs is likely to lead to weaker treatment responses than would be expected in st and ard clinical practice , in which patients are unlikely to doubt that they have been given an active treatment .
Conclusions Participants ’ expectancies can undermine the validity of double-blind placebo-controlled RCTs .