Sham Arm Research Articles

Resolving Paradoxes in Acupuncture Research: A Roundtable Discussion

Peter M. Wayne: We’re going to be discussing the workshop that we held at the North American Research Conference on Complementary and Integrative Medicine (NARCCIM) in May 2009. The workshop was designed to present the findings from a Society for Acupuncture Research (SAR) board retreat, which focused on ‘‘Paradoxes in Acupuncture Research: Strategies for Moving Forward.’’ The paradoxes, in turn, had emerged during the 2007 SAR International Conference that reviewed the progress in our field in the decade since the 1997 NIH Consensus Development Conference on Acupuncture. The conference was a great success, with more than 300 attendees and support from the National Institutes of Health (NIH), conventional medical schools, schools of acupuncture and Oriental medicine, and a variety of other national and international organizations. The conference concluded that the field of acupuncture research had made great progress since 1997. Many rigorous phase II and III randomized controlled trials were completed for acupuncture treatment of a wide variety of medical conditions, and some very strong basic research was performed with state-of-the-art tools to examine biochemical and physiologic correlates of acupuncture. Important progress was also made with respect to control procedures and other aspects of clinical research design. Summaries of the conference have been published in the Journal of Alternative and Complementary Medicine. But in putting together this work, we identified two paradoxes. Paradox One is that an increasing number of large clinical trials have reported that true acupuncture does not significantly outperform sham acupuncture, a finding apparently at odds with traditional theories regarding acupuncture point specificity and needling techniques. Paradox Two is that while many studies with animal and human experimental models have reported physiologic effects that vary as a function of needling parameters, the extent to which these parameters influence therapeutic outcomes in clinical trials is unclear. As the SAR board prepared a White Paper to highlight these paradoxes and discuss research directions to resolve them, the opportunity arose to present our thinking at the NARCCIM conference. Richard Hammerschlag: That gives us a good sense of where we’re at: How we came to focus on these paradoxes, our work in clarifying them, and the research we’re proposing as necessary to resolve them. Regarding the first paradox, many people, and especially practitioners, were quite disturbed after the 2007 SAR Conference by the conclusion, especially on the basis of the largescale German trials that were presented, that it either doesn’t matter where we place acupuncture needles or that something is amiss with the research design of such studies. As researchers, we need to be open to exploring both possibilities. For me, the question with regard to this paradox is twofold. First, sham needling is not inert and appears to produce a level of benefit that is procedure related. Second, inclusion of a sham-treatment arm in a randomized controlled trial may reduce the level of effectiveness of the active-treatment arm (by reducing patient expectancy of receiving an effective treatment from 100% to 50%). My concern is that by utilizing a control procedure that has treatment benefit and by following a research design that may decrease the effectiveness of a verum or active treatment, we’re generating type II errors and getting false-negative results. For example, sham needling—especially if it’s invasive—may induce microtrauma through local physiologic changes in microcirculation or cytokines that promote healing in the body. A recent review indicates that in acupuncture trials that have had both a sham arm and a nontreatment arm in addition to the active-treatment arm, the difference between the sham and nontreatment arms seems to have been greater than that between the placebo and nontreatment arms in conventional pharmaceutical trials. So this again raises a possibility that sham treatment is not inert, and that some

Acupuncture for chemotherapy-induced neutropenia in patients with gynecologic malignancies: a pilot randomized, sham-controlled clinical trial.

The objective of this study was to investigate the effect of acupuncture administered during myelosuppressive chemotherapy on white blood cell (WBC) count and absolute neutrophil count (ANC) in patients with ovarian cancer. This study is a pilot, randomized, sham-controlled clinical trial. Patients received active acupuncture versus sham acupuncture while undergoing chemotherapy. A standardized acupuncture protocol was employed with manual and electrostimulation. The frequency of treatment was 2-3 times per week for a total of 10 sessions, starting 1 week before the second cycle of chemotherapy. The setting was two outpatient academic centers for patients with cancer. Twenty-one (21) newly diagnosed and recurrent ovarian cancer patients were the subjects. WBC count, ANC, and plasma granulocyte colony-stimulating factor (G-CSF ) were assessed weekly. The median leukocyte value in the acupuncture arm at the first day of the third cycle of chemotherapy was significantly higher than in the control arm after adjusting for baseline value (8600 cells/microL, range: 4800-12,000 versus 4400 cell/microL, range: 2300-10,000) (p = 0.046). The incidence of grade 2-4 leukopenia was less in the acupuncture arm than in the sham arm (30% versus 90%; p = 0.02). However, the median leukocyte nadir, neutrophil nadir, and recovering ANC were all higher but not statistically significantly different (p = 0.116-0.16), after adjusting for baseline differences. There were no statistically significant differences in plasma G-CSF between the two groups. We observed clinically relevant trends of higher WBC values during one cycle of chemotherapy in patients with ovarian cancer, which suggests a potential myeloprotective effect of acupuncture. A larger trial is warranted to more definitively determine the efficacy of acupuncture on clinically important outcomes of chemotherapy-induced neutropenia.

Randomized, blinded, placebo-controlled trial of acupuncture for the management of aromatase inhibitor-associated joint symptoms in women with early-stage breast cancer

571 Background: Aromatase inhibitors (AIs) have become the standard of care for the treatment of postmenopausal, hormone-sensitive breast cancer (BC). However, patients receiving AIs may experience joint symptoms which can lead to early discontinuation of this effective therapy. We examined whether acupuncture improves AI-induced arthralgias in women with early stage BC. Methods: This study is a randomized, single-blinded trial of true vs sham acupuncture twice weekly for 6 weeks in postmenopuasal women with early stage BC and self-reported musculoskeletal pain related to adjuvant AI therapy. The active intervention included full body/auricular acupuncture and a joint-specific point prescription, whereas the sham arm involved superficial needle insertion at nonacupoint locations. Outcome measures included the Brief Pain Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC), and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) obtained at baseline, 3 and 6 weeks. Lower scores reflect improvement in symptoms. Results: Of 43 women enrolled, 38 were evaluable at 6 weeks. Baseline characteristics were comparable between the groups. Median age: 57 (37–77); White/Hispanic/Black/Asian: 15/21/1/1; median body mass index (kg/m2): 29 (18–45). True acupuncture was associated with about a 50% decrease in mean BPI-SF scores, whereas no change from baseline was observed for the sham acupuncture group (see table). Similar findings were seen for the WOMAC and M-SACRAH pain, stiffness, and function scores (P<0.05). No adverse events were reported. Conclusions: Women with AI-induced arthralgias treated with acupuncture had significant improvement of joint pain and stiffness, which was not seen with sham acupuncture. Acupuncture is an effective and well-tolerated strategy for managing this common treatment-related side effect. [Table: see text] No significant financial relationships to disclose.

Endoscopic Therapy for Barrett's Esophagus

Recent retrospective cohort data and a prospective randomized sham controlled trial have clearly documented the impact of endoscopic ablation therapy on dysplasia and Barrett's esophagus (BE). The clinical indications for ablation of BE includes high-grade dysplasia and intramucosal adenocarcinoma. The techniques of resection of mucosal irregularities and of ablation are reviewed, primarily thermal and photodynamic ablation. Ablation of BE with neoplasia has appropriately entered the clinical arena.

Does Therapeutic Touch Ease the Discomfort or Distress of Patients Undergoing Stereotactic Core Breast Biopsy? A Randomized Clinical Trial

To determine whether therapeutic touch administered at the time of stereotactic core biopsy of suspicious breast lesions results in a reduction in anxiety and pain. Randomized, patient-blinded, controlled trial of either Krieger-Kunz therapeutic touch administered by a trained practitioner or a sham intervention mimicking therapeutic touch delivered during core biopsy. Stereotactic breast biopsy unit of a comprehensive breast center. Women with mammographically detected, nonpalpable breast lesions requiring biopsy. Changes in pain and anxiety measured by visual analog scales immediately before and after stereotactic core biopsy. A total of 82 patients were accrued: 42 received actual therapeutic touch and 40 sham therapeutic touch. No significant differences were found between the arms for age, ethnicity, educational background, or other demographic data. The sham arm had a preponderance of left breast biopsies (48% vs 58%; P = 0.07) and received a slightly higher volume of epinephrine-containing local anesthetic (6.5 +/- 6.1 vs 4.5 +/- 4.5 mL; P = 0.09). Therapeutic touch patients were more likely to have an upper breast lesion location (57% vs 53%; P = 0.022). No significant differences between the arms were seen regarding postbiopsy pain (P = 0.95), anxiety (P = 0.66), fearfulness, or physiological parameters. Similarly, no differences were seen between the arms when change in parameters from prebiopsy to postbiopsy was considered for any of the psychological or physiological variables measured. These findings persisted when confounding variables were controlled for. Women undergoing stereotactic core breast biopsy received no significant benefit from therapeutic touch administered during the procedure. Therapeutic touch cannot be routinely recommended for patients in this setting.

An overview of two Cochrane systematic reviews of complementary treatments for chronic asthma: acupuncture and homeopathy

Background: Acupuncture and homeopathy are commonly used complementary treatments for chronic asthma. This review summarizes two recently updated Cochrane systematic reviews that assess the safety and efficacy of homeopathy or acupuncture in individuals with chronic stable asthma. Inclusion criteria: Only randomized-controlled trials were considered for inclusion. Statistical aggregation of the data was undertaken where possible. Search strategy: Searches for both reviews were done with the assistance of the Cochrane Airways Group, and through electronic alerts. Results: Acupuncture: 11 studies with 324 participants met the inclusion criteria. Trial reporting was poor, and the trial quality was deemed inadequate to generalize the findings. There was variation in the type of active and sham acupunctures, the outcomes assessed and the time points measured. The points used in the sham arm of some studies are used for the treatment of asthma according to traditional Chinese medicine. Two studies used individualized treatment strategies, and one study used a combination strategy of formula acupuncture with the addition of individualized points. No statistically significant or clinically relevant effects were found for acupuncture compared with sham acupuncture. When data from two small studies were pooled, no difference in lung function was observed (post-treatment FEV 1): standardized mean difference 0.12, 95% confidence interval −0.31 to 0.55). Conclusion: Acupuncture: There is not enough evidence to recommend the use of acupuncture in the treatment of asthma. Further research needs to be undertaken, and this should take into account the different types of acupuncture practiced. Results: Homeopathy: Six trials with a total of 556 people were included in the review. These trials were all placebo-controlled and double-blind, but were of variable quality. Standardized treatments in these trials are unlikely to represent common homeopathic practice where treatment tends to be individualized. The results of the studies are conflicting in terms of effects on lung function. There has been only a limited attempt to measure a “package of care” effect (i.e. the effect of the medication as well as the consultation, which is considered a vital part of individualized homeopathic practice). Conclusion: Homeopathy: There is not enough evidence to reliably assess the possible role of homeopathy in the treatment of asthma. Further studies could assess whether individuals respond to a “package of care” rather than the homeopathic intervention alone.

Acupuncture for chronic asthma.

Acupuncture has traditionally been used to treat asthma in China and is used increasingly for this purpose internationally. The objective of this review was to assess the effects of acupuncture for the treatment of asthma or asthma-like symptoms. We searched the Cochrane Airways Group trials register (searched August 2003), the Cochrane Complementary Medicine Field trials register, the Alternative Medicine Database (August 2003) and reference lists of articles. We also contacted trialists and researchers in the field of complementary and alternative medical research. Randomised and possibly randomised trials using needle acupuncture or other forms of stimulation of acupuncture. Any form of control treatment was considered (no treatment in addition to conventional asthma treatment, sham or placebo interventions, active comparator interventions). Studies were included provided outcome was assessed at one week or more. At least two reviewers independently assessed trial quality. A reviewer experienced in acupuncture assessed the adequacy of the active and sham acupunctures used in the studies. Study authors were contacted for missing information. Eleven studies met the inclusion criteria with 324 participants. Trial reporting was poor and trial quality was deemed inadequate to generalise findings. There was variation in the type of active and sham acupunctures, the outcomes measured and time-points presented. The points used in the sham arm of some studies are used for the treatment of asthma according to traditional Chinese medicine. Two studies used individualised treatment strategies and one study used a combination strategy of formula acupuncture with the addition of individualised points. No statistically significant or clinically relevant effects were found for acupuncture compared to sham acupuncture. Data from two small studies were pooled for lung function (post-treatment FEV1): Standardised Mean Difference 0.12, 95% confidence interval -0.31 to 0.55). There is not enough evidence to make recommendations about the value of acupuncture in asthma treatment. Further research needs to consider the complexities and different types of acupuncture.

6995 A novel method to reduce post-ercp pancreatitis in patients with sphincter of oddi dysfunction: botulinum toxin injection of the residual pancreatic sphincter.

Background: Endoscopic biliary sphincterotomy in sphincter of Oddi dysfunction (SOD) patients has a high risk of post-ERCP pancreatitis. It is hypothesized that this high complication rate is due to residual pancreatic sphincter hypertension. Aim: To decrease the pancreatitis rate of SOD patients after biliary sphincterotomy by injecting botulinum toxin into the residual pancreatic sphincter. This is technically simpler and involves less pancreatic manipulation than pancreatic stent placement. Methods: All patients undergoing ERCP with manometry for suspicion of biliary SOD where asked to participate in this study. Manometry was performed to obtain baseline biliary and pancreatic sphincter pressures with at least two pull-through recordings. Patients with normal basal pressures (less than 40 mmHg) were excluded. Those with elevated pressures were randomized to receive botulinum toxin vs. sham saline injection after the biliary sphincterotomy. Fifty units of botulinum toxin was delivered via sclerotherapy needle as two 25 U injections of 0.25cc each into the pancreatic sphincter in the botulinum toxin therapy group. For those in the sham arm, 0.50cc of saline was injected into the duodenal lumen via sclerotherapy needle. All patients were assessed 24 hours post-procedure for complications. Results: Between 2/12/99 and 11/30/99 a total of 57 patients were referred for ERCP with manometry for suspected SOD. Fifty-one consented to participate in the protocol. Thirteen had elevated baseline pressures and were randomized. Six received botulinum toxin injection and 7 were randomized to sham injection. A total of 4 (57%) patients in the sham group developed procedure-induced pancreatitis as compared to 2 (33%) in the botulinum toxin group (NS). No differences were observed in the severity of pancreatitis between the groups. Conclusions: In the small number of patients studied to date, no definite conclusion can be made about the effect of botulinum toxin injection on the pancreatitis rate of SOD patients following biliary sphincterotomy.

Acupuncture for chronic asthma.

Acupuncture has traditionally been used to treat asthma in China and is used increasingly for this purpose internationally. The objective of this review was to assess the effects of acupuncture for the treatment of asthma or asthma-like symptoms. We searched the Cochrane Airways Group trials register, the Cochrane Complementary Medicine Field trials register and reference lists of articles. Randomised and possibly randomised trials using acupuncture to treat asthma and asthma-like symptoms. Acupuncture could involve the insertion of needles or other forms of stimulation of acupuncture points. Trial quality was assessed by at least two reviewers independently. A reviewer experienced in acupuncture assessed the adequacy of the sham acupuncture. Study authors were contacted for missing information. Seven trials involving 174 people were included. Trial quality varied and results were inconsistent. No statistically significant or clinically relevant effects were found for acupuncture compared to sham acupuncture. However the points used in the sham arm of some studies are used for the treatment of asthma according to traditional Chinese medicine. Only one study used individualised treatment strategies. Lung function could be compared statistically in only 3 trials. Peak expiratory flow rate showed a statistically insignificant increase of 8.4 litres/minute weighted mean difference (95% confidence interval -29.4 to 46.2) when acupuncture was compared to sham acupuncture. There is not enough evidence to make recommendations about the value of acupuncture in asthma treatment. Further research needs to consider the complexities and different types of acupuncture.