Placebo Surgery Research Articles

Surgical Treatment of Lateral Epicondylitis: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial

Background: A number of surgical techniques for managing tennis elbow have been described. One of the most frequently performed involves excising the affected portion of the extensor carpi radialis brevis (ECRB). The results of this technique, as well as most other described surgical techniques for this condition, have been reported as excellent, yet none have been compared with placebo surgery. Hypothesis: The surgical excision of the degenerative portion of the ECRB offers no additional benefit over and above placebo surgery for the management of chronic tennis elbow. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: This study investigated surgical excision of the macroscopically degenerated portion of the ECRB (surgery; n = 13) as compared with skin incision and exposure of the ECRB alone (sham; n = 13) to treat patients who had tennis elbow for >6 months and had failed at least 2 nonsurgical modalities. The primary outcome measure was defined as patient-rated frequency of elbow pain with activity at 6 months after surgery. Secondary outcome measures included patient-rated pain and functional outcomes, range of motion, epicondyle tenderness, and strength at 6 months and 2.5 years. All outcome measures up to and including the 6-month follow-up were measured in person; the longer-term questionnaire was conducted in person or over the phone. Results: The 2 groups, surgery and sham, were similar for age, sex, hand dominance, and duration of symptoms. Both procedures improved patient-rated pain frequency and severity, elbow stiffness, difficulty with picking up objects, difficulty with twisting motions, and overall elbow rating >6 months and at 2.5 years (P < .01). Both procedures also improved epicondyle tenderness, pronation-supination range, grip strength, and modified Orthopaedic Research Institute–Tennis Elbow Testing System at 6 months (P < .05). No significant difference was observed between the groups in any parameter at any stage. No side effects or complications were reported. The study was stopped before the calculated number of patients were enrolled (40 per group); yet, a post hoc futility analysis was conducted that showed, based on the magnitude of the differences between the groups, >6500 patients would need to be recruited per group to see a significant difference between the groups at 26 weeks in the primary outcome (patient-rated frequency of elbow pain with activity). Conclusion: With the number of available participants, this study failed to show additional benefit of the surgical excision of the degenerative portion of the ECRB over placebo surgery for the management of chronic tennis elbow.

Arthroscopic partial meniscectomy versus placebo surgery for a degenerative meniscus tear: a 2-year follow-up of the randomised controlled trial

ObjectiveTo assess if arthroscopic partial meniscectomy (APM) is superior to placebo surgery in the treatment of patients with degenerative tear of the medial meniscus.MethodsIn this multicentre, randomised, participant-blinded and outcome...

Commentary on “A Proposed Road Map for the Ethical Evaluation of Sham (Placebo) Surgery”

Commentary on “A Proposed Road Map for the Ethical Evaluation of Sham (Placebo) Surgery”

Surgical Treatment of Lateral Epicondylitis

Objectives:A number of surgical techniques for managing tennis elbow have been described, one of the commonest (Nirschl & Pettrone. J Bone Joint Surg Am, 61(6A): 832-839) involves excising the affected portion of extensor carpi radialis brevis (ECRB) origin. The results of this technique, as well as most other described surgical techniques for this condition, have been reported as excellent, yet none have been compared with placebo surgery.Methods:This study was a prospective, randomised, double blinded, placebo controlled clinical trial investigating the surgical excision of the macroscopically degenerated portion of ECRB (Nirschl technique; n=13) compared with a sham operation (skin incision and exposure of ECRB alone; n=13) to manage tennis elbow, in patients with tennis elbow for more than 6 months who failed at least two non-surgical modalities. The primary outcome measure was defined as patient rated frequency of elbow pain with activity at 6 months post-surgery. Secondary outcome measures included patient rated frequency and severity of pain, functional outcomes, range of motion, epicondyle tenderness and strength at 6 months and >12 months post-surgery.Results:The two groups were matched for age, gender, hand dominance and duration of symptoms. Both the surgery and placebo procedures improved patient rated pain frequency and severity, elbow stiffness, difficulty with picking up objects, twisting motions and overall elbow rating over 6 months and at >12 months (p<0.01). Both procedures also improved epicondyle tenderness, pronation-supination range, grip strength and modified ORI-TETS at 6 months (p<0.05). No significant difference was observed between the groups in any parameter at any stage. No side effects or complications were reported. The study was stopped before the calculated number of patients were enrolled, as a post-hoc analysis showed over 6500 patients would need to be recruited in each group to see a significant difference between the groups at 26 weeks, when measuring patient rated frequency of elbow pain with activity.Conclusion:This study indicates that the surgical excision of the degenerative portion of ECRB offers no additional benefit over and above placebo surgery for the management of chronic tennis elbow.Frequency of pain with activity. Mean (SEM), n=13 for each group, * = p<0.05, ** = p<0.01, *** = p<0.001 compared with time 0w using Wilcoxon signed rank sum tests

A MEASURE FOR ESTIMATING THE MAGNITUDE OF UNNECESSARY OVERTREATMENT, OVER TESTING AND OVER PREVENTING

There is not any summary measure in EBM for showing the magnitude of unnecessary medical interventions including overtreatment, over testing and over preventing. Based on the finding of a valid...

Surgical treatment of lateral epicondylitis: A prospective, randomised, double blinded, placebo controlled clinical trial

Introduction: A number of surgical techniques for managing tennis elbow have been described, one of the commonest (Nirschl and Pettrone, J Bone Joint Surg Am 61(6A):832–-839) involves excising the affected portion of ECRB. The results of this technique, as well as most other described surgical techniques for this condition, have been reported as excellent, yet none have been compared with placebo surgery.

Surgical options for lumbar spinal stenosis.

Surgical options for lumbar spinal stenosis.

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Behavioural effects of epilepsy surgery.

There are relatively few studies of the behavioural outcome of epilepsy surgery in children that have used standardised behavioural measures before and after the procedure. Those investigations that have used such measures are often on mixed groups with mixed pathology, implying that the numbers, when stratified, are very small. They are also often retrospective. Furthermore, because placebo surgery is generally not an option, the studies have been open and they are usually uncontrolled. The few available data suggest that, although individual children may benefit or deteriorate, there is little overall group effect of temporal or extratemporal surgery on behavioural/psychiatric outcome. Hemispherectomy has traditionally been associated with the expectation of marked behavioural improvement but firm data are lacking. Multiple subpial transection performed for electrical status epilepticus of slow-wave sleep in the Landau-Kleffner syndrome can result in marked improvements in cognition and behaviour. Vagus nerve stimulation appears to improve quality of life and mood/behaviour but again the quality of the data has been questioned. There is a need for large, prospective, multicentre, collaborative studies using standardised cognitive and behavioural measures before and after surgery to provide an adequate database on the outcome of various categories of procedures, pathologies and patients.

When should placebo surgery as a control in clinical trials be carried out?

When should placebo surgery as a control in clinical trials be carried out?

When should placebo surgery as a control in clinical trials be carried out?

Placebo surgery – often maligned as ‘sham surgery’ – is a tough sell to patients and to many clinicians. But could surgical research benefit from increased use of placebo control groups?

Position Statement: Use of placebo surgery in surgical research

Position Statement: Use of placebo surgery in surgical research

Vertebral Augmentation for Osteoporotic Compression Fractures: Review of the Fracture Reduction Evaluation Trial.

Osteoporotic vertebral compression fractures affect more than 1 million patients worldwide each year. Percutaneous balloon kyphoplasty is a minimally invasive vertebral augmentation procedure that aims to stabilize fractured vertebral compression fractures rapidly and improve spinal deformity. The Fracture Reduction Evaluation (FREE) trial was the first randomized trial to compare balloon kyphoplasty against nonoperative management and it remains a landmark trial today. On the basis of this single trial, the American Academy of Orthopaedic Surgeons made a "weak" recommendation that "kyphoplasty is an option" for patients presenting with osteoporotic vertebral compression fractures. Ongoing controversy remains about the effectiveness of this technique compared with placebo or sham surgery and other vertebral augmentation procedures. Economic analyses suggest that kyphoplasty is cost-effective, but complication rates and long-term outcomes remain poorly defined.

Knee arthroscopies: who gets them, what does the radiologist report, and what does the surgeon find?

Background and purpose — Several randomized controlled trials have not shown any added benefit of arthroscopy over placebo surgery or physiotherapy in middle-aged patients with knee symptoms without trauma. We studied the characteristics of the knee arthroscopies performed in southern Sweden.Patients and methods — From the orthopedic surgical records from 2007–2009 in the Skåne region of Sweden (with a population of 1.2 million), we retrieved ICD-10 diagnostic codes and selected all 4,096 arthroscopies that were diagnosed peroperatively with code M23.2 (derangement of meniscus due to old tear or injury) or code M17 (knee osteoarthritis). We extracted information on cartilage and meniscus status at arthroscopy, and we also randomly sampled 502 of these patients from the regional archive of radiology and analyzed the preoperative prevalence of radiographic or magnetic resonance imaging (MRI)-defined osteoarthritis.Results — 2,165 (53%) of the 4,096 arthroscopies had the diagnostic code M23.2 or M17. In this subgroup, 1,375 cases (64%) had typical findings consistent with degenerative meniscal tear (i.e. that correspond to a degenerative meniscal tear in at least a third of all arthroscopies). Of the randomly sampled patients, the preoperative prevalence of radiological knee osteoarthritis was 46%.Interpretation — There is a discrepancy between evidence-based medicine treatment guidelines and clinical practice regarding the amount of knee arthroscopies performed in patients with symptoms of degenerative knee disease.

Placebo Surgery in Clinical Research Trials for Parkinson Disease

Advances in the field of neurology and neurosurgery have contributed to the development of novel approaches in the treatment of motor symptoms of Parkinson disease (PD). Comparative trials have been performed in PD to evaluate the efficacy of implanted fetal tissue against the standard of care and placebo surgery. Placebo surgery is when a research subject undergoes a surgical procedure that has the appearance of a therapeutic intervention but during which the essential therapeutic maneuver is omitted and is used as the control arm of the research trial. The purpose of this article is to allow nurse practitioners to review the use of placebo surgery as a control arm in the treatment of PD. The potential of transplantation surgeries to improve the lives of those living with neurodegenerative conditions is a fascinating and promising avenue of medical exploration. An overview of clinical trials in which placebo surgery is used as a control is discussed in this article along with the Common Rule and ethical principles to ensure the protection of human subjects in clinical research.

Strengthening the ethical assessment of placebo-controlled surgical trials: three proposals.

BackgroundPlacebo-controlled surgical trials can provide important information about the efficacy of surgical interventions. However, they are ethically contentious as placebo surgery entails the risk of harms to recipients, such as pain, scarring or anaesthetic misadventure. This has led to claims that placebo-controlled surgical trials are inherently unethical. On the other hand, without placebo-controlled surgical trials, it may be impossible to know whether an apparent benefit from surgery is due to the intervention itself or to the placebo effect.DiscussionIn this paper we investigate justifications for placebo-controlled surgical trials and suggest three measures for strengthening their ethical acceptability. We argue that, given the extent, irreversibility and cost of surgical interventions, there is a need for the best possible evidence about their efficacy. In some cases, the strongest evidence will be from placebo-controlled surgical trials, especially where interventions are for outcomes (such as pain) that are likely to elicit a placebo response. In the second part of the paper, we propose three specific measures to increase the ethical acceptability of placebo-controlled surgical trials. The first is structured consultation with the relevant patient community about the risks and benefits of particular placebo-controlled surgical trials. The second seeks to address the therapeutic misconception through the use of educational materials, informed by patient consultation. Finally, we argue for ethical consideration of non-surgeon clinicians who are necessarily involved in the delivery of placebo-surgical interventions.SummaryIf there is no appropriate surgical comparator and the risks can be reduced to the absolute minimum (given the type of placebo procedure required), and the research has the support of the relevant patient community, there may be grounds for judging that the potential benefits of specific placebo-controlled surgical trials outweigh the risks. If so justified, the ethical acceptability of placebo-controlled surgical trials can be enhanced through using educational measures to address participant vulnerability, and by recognizing clinicians who are necessary participants in the research.

The challenge of recruiting patients into a placebo-controlled surgical trial.

BackgroundRandomized placebo-controlled trials represent the gold standard in evaluating healthcare interventions but are rarely performed within orthopedics. Ethical concerns or well-known challenges in recruiting patients for surgical trials in general have been expressed and adding a placebo component only adds to this complexity. The purpose of this study was to report the challenges of recruiting patients into an orthopedic placebo-controlled surgical trial, to determine the number of patients needed to be screened and allocated in order to include one participant into the trial, and to identify reasons associated with participation in a placebo-controlled randomized surgical trial.MethodsData were extracted from an ongoing placebo-controlled randomized controlled trial (RCT) on meniscectomy versus placebo surgery. We calculated the number of patients needed to be screened in order to include the required number of participants into the RCT. Participating patients were asked about their rationale for joining the study and which type of information was most useful for deciding upon participation.ResultsA total of 476 patients entered the screening group, of which 190 patients fulfilled the inclusion and exclusion criteria. 102 patients declined to participate in the study due to various reasons and 46 were later excluded (no meniscus lesion on the magnetic resonance imaging scan or withdrawn consent). A total of 40 patients were finally included in the RCT. To include one patient into the RCT, 11.9 individuals needed to be screened. A total of 69% of participating patients considered the oral information to be the most important and the most common reason for participating was the contribution to research (90%).ConclusionsPatients are willing to participate in an orthopedic placebo-controlled surgical trial. Oral information given by the surgeon to the patient and the contribution to research are important aspects to enhance patient recruitment.Trial registrationClinicalTrials.gov NCT01264991, registered 21 December 2010.

Attitudes and Beliefs about Placebo Surgery among Orthopedic Shoulder Surgeons in the United Kingdom

ObjectivesTo survey surgeons on their beliefs and attitudes towards the use of placebo in surgery.MethodsBritish orthopedic shoulder surgeons, attending a national conference in the United Kingdom, were asked to complete a self-report online questionnaire about their beliefs and attitudes towards the use of placebo related to surgical intervention. The survey included questions about ethical issues, the mechanism of placebo effects, and any concerns regarding its use.Results100 surgeons who participated in the survey believed that placebo surgery is ethically acceptable (96%), especially as a part of a clinical trial (46%). Respondents thought that a placebo effect in surgery is real i.e. has a scientific basis (92%), that placebo can be therapeutically beneficial (77%), and that it involves psychological mechanisms (96%). Over half of the respondents (58%) have used a surgical procedure with a significant placebo component at least once in their professional career. Their main concern about placebo use in surgery was that it might involve an element of deception.Conclusions and ImplicationsSurgeons generally agreed that a placebo component to surgical intervention might exist. They also supported placebo use in clinical trials and considered it ethical, providing it does not involve deception of patients. More studies are needed, particularly among other surgical specialties and with larger numbers of participants, to better understand the use of placebo in surgery.

Developmental Disorders of the Ear in Children and Adolescents

Developmental disorders of the ear can impair hearing and cause cosmetic deformities. In recent years, new surgical treatments have become established, above all in audiological rehabilitation. We selectively searched the PubMed database up to May 2013 for publications in English and Germanabout the therapeutic options. No randomized trials have been performed, for both ethical and practical reasons (inadmissibility of placebo surgery, specialization of surgeons for individual techniques). To correct prominent ears, cartilage-sparing suture techniques are preferred, as they lead less often than scoring and incisional techniques to the formation of persistent, incompletely correctable ridges and scaffolding defects. The successful esthetic rehabilitation of severe deformities of the external ear is achievable through pinna reconstruction with costal cartilage (main risks: tissue defect at donor site, scaffolding resorption) or porous polyethylene (main risk: implant extrusion). The functional rehabilitation of conductive or mixed hearing impairment due to ear-canal atresia and major middle-ear deformities is preferably achieved with active middle-ear implants or bone-conduction hearing aids. Functional rehabilitation should be provided even when the hearing impairment is unilateral, in order to improve directional hearing and hearing with ambient noise. In cases of purely cochlear, unilateral, severe hearing impairment or deafness, a boneconduction hearing aid can be tried, and the individual indication for a cochlear implant can be considered. The treatment options described here enable the affected children to benefit from complete functional and esthetic rehabilitation before they start school.

Accounting for the placebo effect of surgery in surgical trials?

Compared to pharmacology, the efficacy of surgery has been very poorly evaluated. Many surgical procedures are carried out on a daily basis without any good evidence to support them. Primarily this is because the methodology for surgical trials offers some unique challenges. Whilst a comparison between two (or more) surgical procedures is possible, such a model only provides information on relative efficacy. It does not address the fundamental issue of whether the treatment provides any more benefit than the significant effect obtained from undergoing a surgical procedure. A controlled comparison is therefore preferred, but there are several ethical, implementation and interpretation obstacles to overcome before the design can be accepted as standard. Using a current example of a controlled surgical trial of shoulder surgery (CSAW), a number of issues surrounding controlled surgical trials will be explored. These will include; which designs can be used to account for the effect, what constitutes placebo surgery, how to identify and manipulate the critical surgical element (CSE) and operational problems associated with surgical trials. The objective of the paper is to share recent experiences and derived knowledge to help with future controlled surgical trial design.

Meta-analyses: does long-term PPI use increase the risk of gastric premalignant lesions?

Proton pump inhibitors (PPIs) are the most effective agents available for reducing acid secretion. They are used for medical treatment of various acid-related disorders. PPIs are used extensively and for extended periods of time in gastroesophageal reflux disease (GERD). A troublesome issue regarding maintenance therapy has been the propensity of PPI-treated patients to develop chronic atrophic gastritis while on therapy that could theoretically lead to an increased incidence of gastric cancer. In addition, animal studies have raised concern for development of enterochromaffin-like cell hyperplasia and carcinoid tumors in the stomachs of mice receiving high dose PPIs. Current literature does not provide a clear-cut conclusion on the subject and the reports are sometimes contradictory. Therefore, this study is a systematic review of the available literature to address the safety of long-term PPI use and its relation to the development of malignant/premalignant gastric lesions. A literature search of biomedical databases was performed. The reference lists of retrieved articles were reviewed to further identify relevant trials. We hand-searched the abstracts of the American Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW) from 1995 to 2013. Only randomized clinical trials (RCTs) that used PPIs as the primary treatment for at least six month versus no treatment, placebo, antacid or anti-reflux surgery (ARS) were included. Two reviewers independently extracted the data. Discrepancies in the interpretation were resolved by consensus. All analyses of outcomes were based on the intention-to-treat principle. We performed statistical analysis using Review Manager software. The effect measure of choice was relative risk (RR) for dichotomous data. Six RCTs with a total of 785 patients met the inclusion criteria. Two multicenter RCTs compared Esomeprazole with placebo. One RCT compared omeprazole with ARS. Two RCTs compared omeprazole with ranitidine and one RCT compared lansoprazole with ranitidine. Four of the included RCTs had moderate risk of bias and two had low risk of bias. The number of patients with increased corporal atrophy score, intestinal metaplasia score and chronic antral inflammation did not statistically differ between the PPI maintenance group and controls. Similar results were found when ECL-cell hyperplasia was assessed between the groups. Maintenance PPIs did not have an association with increased gastric atrophic changes or ECL-cell hyperplasia for at least three years in RCTs.