Use of placebo controls in the evaluation of surgery: systematic review.
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ABSTRACT: Objective
To investigate whether placebo controls should be used in the evaluation of surgical interventions.Design
Systematic review.Data sources
We searched Medline, Embase, and the Cochrane Controlled Trials Register from their inception to November 2013.Study selection
Randomised clinical trials comparing any surgical intervention with placebo. Surgery was defined as any procedure that both changes the anatomy and requires a skin incision or use of endoscopic techniques.Data extraction
Three reviewers (KW, BJFD, IR) independently identified the relevant trials and extracted data on study details, outcomes, and harms from included studies.Results
In 39 out of 53 (74%) trials there was improvement in the placebo arm and in 27 (51%) trials the effect of placebo did not differ from that of surgery. In 26 (49%) trials, surgery was superior to placebo but the magnitude of the effect of the surgical intervention over that of the placebo was generally small. Serious adverse events were reported in the placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%); in four trials authors did not specify in which arm the events occurred. However, in many studies adverse events were unrelated to the intervention or associated with the severity of the condition. The existing placebo controlled trials investigated only less invasive procedures that did not involve laparotomy, thoracotomy, craniotomy, or extensive tissue dissection.Conclusions
Placebo controlled trial is a powerful, feasible way of showing the efficacy of surgical procedures. The risks of adverse effects associated with the placebo are small. In half of the studies, the results provide evidence against continued use of the investigated surgical procedures. Without well designed placebo controlled trials of surgery, ineffective treatment may continue unchallenged.
SUBMITTER: Wartolowska K
PROVIDER: S-EPMC4029190 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPoorly described placebo/sham controls make it difficult to appraise active intervention benefits and harms. The 12-item Template for Intervention Description and Replication (TIDieR) checklist was developed to improve the reporting of active interventions. The extent to which TIDieR has been used to improve description of placebo or sham control is not known.Materials and methodsWe systematically identified and examined all placebo/sham-controlled randomised trials published in 2018 in the top six general medical journals. We reported how many of the TIDieR checklist items were used to describe the placebo/sham control(s). We supplemented this with a sample of 100 placebo/sham-controlled trials from any journal and searched Google Scholar to identify placebo/sham-controlled trials citing TIDieR.ResultsWe identified 94 placebo/sham-controlled trials published in the top journals in 2018. None reported using TIDieR, and none reported placebo or sham components completely. On average eight TIDieR items were addressed, with placebo/sham control name (100%) and when and how much was administered (97.9%) most commonly reported. Some items (rationale, 8.5%, whether there were modifications, 25.5%) were less often reported. In our sample of less well-cited journals, reporting was poorer (average of six items) and followed a similar pattern. Since TIDieR's first publication, six placebo-controlled trials have cited it according to Google Scholar. Two of these used the checklist to describe placebo controls; neither one completely desribed the placebo intervention.ConclusionsPlacebo and sham controls are poorly described within randomised trials, and TIDieR is rarely used to guide these descriptions. We recommend developing guidelines to promote better descriptions of placebo/sham control components within clinical trials.
| S-EPMC6819221 | biostudies-literature
Project description:Study Design?Combination of narrative and systematic literature reviews. Objectives?Massive perioperative blood loss in complex spinal surgery often requires blood transfusions and can negatively affect patient outcome. Systemic use of the antifibrinolytic agent tranexamic acid (TXA) has become widely used in the management of surgical bleeding. We review the clinical evidence for the use of intravenous TXA as a hemostatic agent in spinal surgery and discuss the emerging role for its complementary use as a topical agent to reduce perioperative blood loss from the surgical site. Through a systematic review of published and ongoing investigations on topical TXA for spinal surgery, we wish to make spine practitioners aware of this option and to suggest opportunities for further investigation in the field. Methods?A narrative review of systemic TXA in spinal surgery and topical TXA in surgery was conducted. Furthermore, a systematic search (using PRISMA guidelines) of PubMed (MEDLINE), EMBASE, and Cochrane CENTRAL databases as well as World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov (National Institutes of Health), and International Standard Randomized Controlled Trial Number registries was conducted to identify both published literature and ongoing clinical trials on topical TXA in spinal surgery. Results?Of 1,631 preliminary search results, 2 published studies were included in the systematic review. Out of 285 ongoing clinical trials matching the search criteria, a total of 4 relevant studies were included and reviewed. Conclusion?Intravenous TXA is established as an efficacious hemostatic agent in spinal surgery. Use of topical TXA in surgery suggests similar hemostatic efficacy and potentially improved safety as compared with intravenous TXA. For spinal surgery, the literature on topical TXA is sparse but promising, warranting further clinical investigation and consideration as a clinical option in cases with significant anticipated surgical site blood loss.
| S-EPMC4836933 | biostudies-other
Project description:BackgroundThe Pharmaceutical industry sponsorship, research outcome and quality has been already evaluated for clinical trials in order to analyze if this kind of sponsorship affects the results of clinical trials. In this sense, this study has the aim to investigate whether placebo use allows positive outcomes regarding efficacy and safety compared to synthetic medicines.MethodsWe designed and registered a study protocol for a systematic review for methodology data. We will only randomized clinical trials that use placebo as comparator. The main outcome will be the evaluation of placebo use regarding the tendency for positive results (efficacy and security) when comparing to synthetic medicines. PubMed, Cochrane, LILACS (BVS), Web of Science, Scopus, and Excerpta Medica dataBASE (EMBASE) databases will be searched. Gray literature will be identified through the databases Proquest (Dissertation and Theses), OpenGrey and Google Scholar. Two review authors will independently assess trial quality and will extract data in accordance with standard Cochrane methodology. If necessary, we will also contact authors for additional information. The Cochrane Collaboration's risk of bias tool will be used. If feasible, it means homogenous data, we will conduct random effects meta-analysis. Subgroup analyses will be conducted for different justifications for placebo use and for studies sponsored/not sponsored by the pharmaceutical industry.ResultsOur present findings will indicate the effects of placebo use as comparator regarding efficacy and safety of the oral synthetic medicines.DiscussionThis systematic review will identify, summarize, and analyze if there is a trend for positive efficacy and safety results for synthetic medicines in clinical trials when compared with placebo and if the justification for placebo use is considered ethically acceptable.Systematic review registrationPROSPERO CRD42018110829.
| S-EPMC7598826 | biostudies-literature
Project description:BACKGROUND:Common complications of pediatric strabismus surgery, including emergence agitation (EA), postoperative nausea and vomiting (PONV), and postoperative pain, may be prevented using dexmedetomidine, which is an anxiolytic and analgesic. This systematic review and meta-analysis assessed the effects of dexmedetomidine in patients who had undergone pediatric strabismus surgery. METHOD:Five databases were searched for randomized controlled trials published from database inception to April 2020 that compared dexmedetomidine use with placebo or active comparator use and evaluated EA, PONV, or postoperative pain incidence (main outcomes) in patients who had undergone pediatric strabismus surgery. Oculocardiac reflex (OCR) incidence and postanesthesia care unit (PACU) stay duration were considered as safety outcomes. All meta-analyses were performed using a random-effects model. RESULTS:In the nine studies meeting our inclusion criteria, compared with placebo use, dexmedetomidine use reduced EA incidence [risk ratio (RR): 0.39; 95% confidence interval (CI): 0.25-0.62, I2 = 66%], severe EA incidence (RR: 0.27, 95% CI: 0.17-0.43, I2 = 0%), PONV incidence (RR: 0.33, 95% CI: 0.21-0.54, I2 = 0%), analgesia requirement (RR: 0.38, 95% CI: 0.25-0.57, I2 = 0%), and pain scores (standardized mean difference: -1.02, 95% CI: -1.44 to -0.61, I2 = 75%). Dexmedetomidine also led to lower EA incidence in the sevoflurane group than in the desflurane group (RR: 0.26 for sevoflurane vs. 0.45 for desflurane). Continuous dexmedetomidine infusion (RR: 0.19) led to better EA incidence reduction than did bolus dexmedetomidine infusion at the end of surgery (RR: 0.26) or during the peri-induction period (RR: 0.36). Compared with placebo use, dexmedetomidine use reduced OCR incidence (RR: 0.63; I2 = 40%). No significant between-group differences were noted for PACU stay duration. CONCLUSION:In patients who have undergone pediatric strabismus surgery, dexmedetomidine use may alleviate EA, PONV, and postoperative pain and reduce OCR incidence. Moreover, dexmedetomidine use does not affect the PACU stay duration.
| S-EPMC7549777 | biostudies-literature
Project description:ObjectivesTo examine key methodological considerations for using a placebo intervention in randomized controlled trials (RCTs) evaluating invasive procedures, including surgery.Study design and settingRCTs comparing an invasive procedure with a placebo were included in this systematic review. Articles published from database inception to December 31, 2017, were retrieved from Ovid MEDLINE, Ovid EMBASE and CENTRAL electronic databases, by handsearching references and expert knowledge. Data on trial characteristics (clinical area, nature of invasive procedure, number of patients and centers) and key methodological (rationale for using placebos, minimization of risk, information provision, offering the treatment intervention to patients randomized to placebo, delivery of cointerventions, and intervention standardization and fidelity) were extracted and summarized descriptively.ResultsOne hundred thirteen articles reporting 96 RCTs were identified. Most were conducted in gastrointestinal surgery (n = 40, 42%) and evaluated minimally invasive procedures (n = 44, 46%). Over two-thirds randomized fewer than 100 patients (n = 65, 68%) and a third were single center (n = 31, 32%). A third (n = 33, 34%) did not report a rationale for using a placebo. Most common strategies to minimize patient risk were operator skill (n = 22, 23%) and independent data monitoring (n = 28, 29%). Provision of patient information regarding placebo use was infrequently reported (n = 11, 11%). Treatment interventions were offered to patients randomized to placebo in 43 trials (45%). Cointerventions were inconsistently reported, but 64 trials (67%) stated that anesthesia was matched between groups. Attempts to standardize interventions and monitor their delivery were reported in n = 7, (7%) and n = 4, (4%) trials, respectively.ConclusionMost placebo-controlled trials in surgery evaluate minor surgical procedures and currently there is inconsistent reporting of key trial methods. There is a need for guidance to optimize the transparency of trial reporting in this area.
| S-EPMC7066579 | biostudies-literature
Project description:To review the literature evaluating the effect of practice guidelines and decision aids on use of surgery and regional variation.The use of surgical procedures varies widely across geographic regions. Although practice guidelines and decision aids have been promoted for reducing variation, their true effectiveness is uncertain.Studies evaluating the influence of clinical practice guidelines or consensus statements, shared decision making and decision aids, or provider feedback of comparative utilization, on rates of surgical procedures were identified through literature searches of Ovid MEDLINE, EMBASE, and Web of Science.A total of 1946 studies were identified and 27 were included in the final review. Of the 12 studies evaluating implementation of guidelines, 6 reported a significant effect. Those examining overall population-based rates had mixed effects, but all studies evaluating procedure choice described at least a small increase in use of recommended therapy. Three of 5 studies examining the effect of guidelines on regional variation reported a significant reduction after dissemination. Of the 15 studies examining decision aids, 5 revealed significant effects. Many studies of decision aids reported decreases in population-based procedure rates. Nearly all studies evaluating the impact of decision aids on procedure choice reported increases in rates of less invasive procedures. Only one study of decision aids assessed changes in regional variation and found mixed results.Both practice guidelines and decision aids have been proven effective in many clinical contexts. Expanding the clinical scope of these tools and eliminating barriers to implementation will be essential to further efforts directed toward reducing regional variation in the use of surgery.
| S-EPMC4243036 | biostudies-literature
Project description:BackgroundThe use of placebo interventions outside clinical trials is ethically, professionally and legally controversial. Little is known about the frequency and circumstances of placebo use in clinical practice. Our aim was to summarize the available empirical studies addressing these issues.MethodsWe searched PubMed and EMBASE from inception to July 2009 in order to identify cross-sectional surveys, qualitative or longitudinal studies among health care professionals, students or patients which investigated at least one of the following issues--frequency of placebo use or attitudes to, or motivations for, the use of placebo interventions. At least two reviewers extracted information on the study methods, participants and findings. Descriptive summaries were prepared in an iterative process by at least two reviewers per study.ResultsTwenty-two studies from 12 different countries met the inclusion criteria. Most studies had relevant shortcomings. The proportion of respondents reporting that they had applied 'pure' placebos (for example, saline injection) during their professional life varied between 17% and 80% among physicians and between 51% and 100% among nurses, but it seems that the actual frequency of such use seems to be rare. The use of 'impure' or 'active' placebos (for example, antibiotics for viral infections) is likely to be much more frequent. However, it is impossible to make a reliable estimation because there is no agreement of what an impure placebo might be. Studies using qualitative methods or asking participants to judge case examples suggest that motivations and attitudes towards placebo use are complex and health care providers are often faced with a dilemma.ConclusionsAlthough the available evidence is incomplete and confusing at times there can be little doubt that the prevalence of placebo use outside of clinical trials is not negligible and that views and attitudes on placebos use differ considerably among individuals, both health care professionals and patients. Further research is needed to clarify these issues.
| S-EPMC2837612 | biostudies-literature
Project description:BackgroundTranexamic acid (TXA) is well-established as a versatile oral, intramuscular, and intravenous (IV) antifibrinolytic agent. However, the efficacy of IV TXA in reducing perioperative blood transfusion in spinal surgery is poorly documented.MethodologyWe conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-randomized (qi-RCTs) trials that included patients for various spinal surgeries, such as adolescent scoliosis surgery administered with perioperative IV TXA according to Cochrane Collaboration guidelines using electronic PubMed, Cochrane Central Register of Controlled Trials, and Embase databases. Additional journal articles and conference proceedings were manually located by two independent researchers.ResultsTotally, nine studies were included, with a total sample size of 581 patients. Mean blood loss was decreased in patients treated with perioperative IV TXA by 128.28 ml intraoperatively (ranging from 33.84 to 222.73 ml), 98.49 ml postoperatively (ranging from 83.22 to 113.77 ml), and 389.21 ml combined (ranging from 177.83 to 600.60 ml). The mean volume of transfused packed cells were reduced by 134.55 ml (ranging 51.64 to 217.46) (95% CI; P = 0.0001). Overall, the number of patients treated with TXA who required blood transfusions was lower by 35% than that of patients treated with the comparator and who required blood transfusions (RR 0.65; 95% CI; 0.53 to 0.85; P<0.0001, I(2) = 0%). A dose-independent beneficial effect of TXA was observed, and confirmed in subgroup and sensitivity analyses. A total of seven studies reported DVT data. The study containing only a single DVT case was not combined.ConclusionsThe blood loss was reduced in spinal surgery patients with perioperative IV TXA treatment. Also the percentage of spinal surgery patients who required blood transfusion was significantly decreased. Further evaluation is required to confirm our findings before TXA can be safely used in patients undergoing spine surgery.
| S-EPMC3570541 | biostudies-literature
Project description:ImportanceNonspecific effects, particularly placebo effects, are thought to contribute significantly to the observed effect in surgical trials.ObjectiveTo estimate the proportion of the observed effect of surgical treatment that is due to nonspecific effects (including the placebo effect).Data sourcesPublished Cochrane reviews and updated, extended search of MEDLINE, Embase, and CENTRAL until March 2019.Study selectionPublished randomized placebo-controlled surgical trials and trials comparing the effect of the same surgical interventions with nonoperative controls (ie, no treatment, usual care, or exercise program).Data extraction and synthesisPairs of authors independently screened the search results, assessed full texts to identify eligible studies and the risk of bias of included studies, and extracted data. The proportion of all nonspecific effects was calculated as the change in the placebo control divided by the change in the active surgery and pooled in a random-effect meta-analysis. To estimate the magnitude of the placebo effect, we pooled the difference in outcome between placebo and nonoperative controls and used metaregression to estimate the association between the type of control group and the treatment effect (difference between the groups), adjusting for risk of bias, sample size, and type of outcome.Main outcomes and measuresBetween- and within-group effect sizes expressed as Hedges g.ResultsIn this review, 100 trials were included comprising data from 62 trials with placebo controls (3 also included nonoperative controls), and 38 trials with nonoperative controls (32 interventions; 10 699 participants). Risk of bias across trials was comparable except for performance and detection bias, which was high in trials with nonoperative controls. The mean nonspecific effects accounted for 67% (95% CI, 61% to 73%) of the observed change after surgery; however, this varied widely between different procedures. The estimated surgical placebo effect had a standardized mean difference (SMD) of 0.13 (95% CI, -0.26 to 0.51). Trials with placebo and nonoperative controls found comparable treatment effects (SMD, -0.09 [95% CI, -0.35 to 0.18]; 15 interventions; 73 between-group effects; adjusted analysis: SMD, -0.11 [95% CI, -0.37 to 0.15]).Conclusions and relevanceIn this review, the change in health state after surgery was composed largely of nonspecific effects, but no evidence supported a large placebo effect. Placebo-controlled surgical trials may be redundant when trials with nonoperative controls consistently report no substantial association from surgery compared with nonoperative treatment.
| S-EPMC9331086 | biostudies-literature
Project description:BACKGROUND:The aim of this systematic review and meta-analysis was to evaluate the benefit of platelet rich plasma (PRP) in oral surgery. MATERIALS AND METHODS:We performed a systematic search of the literature. The GRADE system was used to assess the certainty of the body of evidence. RESULTS:We found 21 randomised controlled trials that met our inclusion criteria: 12 studies included patients with periodontal defects, five studies focused on healing of extraction sockets, three studies on sinus lift augmentation, and one study on periapical osseous defects. However, for the quantitative synthesis (meta-analysis), we evaluated "periodontal defects" studies only, since for other clinical contexts the number of studies were too low and the procedural heterogeneity was too high to allow pooling of data. PRP-containing regimens were compared to non-PRP-containing regimens. Primary outcomes for the evaluation of periodontal defects were probing depths, clinical attachment level, gingival recession, and radiographic bone defect. It is not usually clear whether or not the use of PRP compared to controls affects "probing depth" at long-term follow up; the between group differences were small and unlikely to be of clinical importance (i.e., very low quality of evidence). For the other outcomes analysed ("clinical attachment levels", "gingival recession", "bony defect"), we observed a very slight marginal clinical benefit of PRP compared to controls. The available evidence for these comparisons was rated as low quality as most of the studies selected showed inconsistency, imprecision, and risk of bias. DISCUSSION:Evidence from a comparison between the use in oral surgery of PRP-containing regimens compared to other regimens not-containing PRP was of low quality. The results of the meta-analysis, limited to studies in patients with periodontal defects, document that PRP was slightly more effective compared to controls not-containing PRP.
| S-EPMC6774927 | biostudies-literature