Although many researchers agree that applying conventional drug-trial quality criteria to CAM studies lacks plausibility, few take on the burden of devising alternative criteria in a specific area of CAM. This commentary points out strengths and weaknesses in the approach taken in the work of Mathie and colleagues to do this for homeopathy.

Medical records contain an abundance of information, very little of which is extracted and put to clinical use. Increasing the flow of information from medical records to clinical practice requires methods of analysis that are appropriate for large nonintervention studies. The purpose of this article is to explain in nontechnical language what these methods are, how they differ from conventional statistical analyses, and why the latter are generally inappropriate. This is important because of the current volume of nonintervention study analyses that either use incorrect methods or misuse correct methods. A set of guidelines is suggested for use in nonintervention clinical research.

Methods for analyzing data in nonintervention clinical studies are substantially different from those that are appropriate for randomized clinical trials. Although the latter methods are well known, the former are not. A systematic approach for dealing with statistical confounding in nonintervention research has been developed over the past 30 to 40 years, and the essence of this theory constitutes the contents of this article. An accompanying, less technical article explains the implications of these results for clinical research.

Background

There is a need for more Comparative Effectiveness Research (CER) to strengthen the evidence base for clinical and policy decision-making. Effectiveness Guidance Documents (EGD) are targeted to clinical researchers. The aim of this EGD is to provide specific recommendations for the design of prospective acupuncture studies to support optimal use of resources for generating evidence that will inform stakeholder decision-making.

Methods

Document development based on multiple systematic consensus procedures (written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders including patients, clinicians and payers were involved.

Results

Recommendations focused mainly on randomized studies and were developed for the following areas: overall research strategy, treatment protocol, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication.

Conclusion

The present EGD, based on an international consensus developed with multiple stakeholder involvement, provides the first systematic methodological guidance for future CER on acupuncture.

Objective

There are many commercially available instruments for measuring electrical conductance, but there is little information about their reliability. The aim of this study was to quantify measurement variability and assess reliability of the AcuGraph system—a commonly used electrodermal screening device.

Methods

Four experiments were conducted to measure variability in electrical conductance readings obtained by the AcuGraph system. The fi rst involved measuring known resistors. The second measured non-human organic matter. The third was a test–retest assessment of the Yuan-Source and Jing-Well points in 30 healthy volunteers who were measured by a single operator. The fourth was an interoperator reliability evaluation of seven acupuncturists at the Yuan-Source and Jing-Well acupoints on four individuals at two time points.

Results

Against known resistors, the AcuGraph had an average coeffi cient of variability (CV) of 1.8% between operators and test–retests. On non-human organic material the AcuGraph had an average CV of 0.9% and 2.8%. When a single operator tested 30 participants, the average reliability for the Yuan-Source points was 0.86 and 0.76 for Jing-Well points with a CV of 23.2% and 25.9% respectively. The average CV for the seven acupuncturists was 24.5% on Yuan-Source points and 23.7% on Jing-Well points.

Conclusions

The AcuGraph measures known resistors and organic matter accurately and reliably. Skin conductance at acupoints recorded by one operator was also reliable. There was less consistency in electrodermal recordings obtained by seven different operators. Operator training and technical improvements to the AcuGraph may improve consistency among operators.

Context: Participants in a randomized trial of traditional Chinese medicine (TCM) for temporomandibular joint dysfunction (TMD) had a linear decline in pain over 16 TCM visits.

Objective: To investigate whether reductions in pain among participants receiving TCM can be explained by increased use of pain medications, or whether use of pain medications also declined in this group.

Design: One hundred sixty-eight participants with TMD were treated with TCM or enhanced self-care according to a stepped-care design. Those for whom self-care failed were sequentially randomized to further self-care or TCM. This report includes 111 participants during their first 16 TCM visits. The initial 8 visits occurred more than once a week; participants and practitioners determined the frequency of subsequent visits.

Outcome measures: Average pain (visual analog scale, range 0–10) and morphine and aspirin dose equivalents.

Results: The sample was 87% women and the average age was 44 ± 13 years. Average pain of narcotics users (n = 21) improved by 2.73 units over 16 visits (p < 0.001). Overall narcotics use trended downward until visit 11 (−3.27 doses/week, p = 0.156), and then trended upward until week 16 (+4.29 doses/week, p = 0.264). Among those using narcotics, use of nonsteroidal anti-inflammatory drugs (NSAIDs) declined linearly over visits 1–16 (−1.94 doses/week, p = 0.002).

Among the top quartile of NSAID-only users (n = 22), average pain decreased linearly over 16 visits (−1.52 units, p = 0.036). Overall NSAID doses/week declined between visits 1 and 7 (−9.95 doses/week, p < 0.001) and then remained stable through 16 visits. NSAID use also declined among the third quartile (n = 23) and remained low and stable among the lower half (sorted by total intake) of NSAID users.

Conclusions: Among the heaviest NSAID users, we observed a short-term reduction in NSAID use that was sustained as TCM visits became less frequent. There was no indication that pain reduction during TCM treatment was influenced by drug use.

Background

Homeopathy, a common form of alternative medicine worldwide, relies on subjective patient reports for diagnosis and treatment. Polysomnography offers a modern methodology for evaluating the objective effects of taking homeopathic remedies that clinicians claim exert effects on sleep quality in susceptible individuals. Animal studies have previously shown changes in non rapid eye movement sleep with certain homeopathic remedies.

Methods

Young adults of both sexes (ages 18–31) with above-average scores on standardized personality scales for either cynical hostility or anxiety sensitivity (but not both), and a history of coffee-induced insomnia, participated in the month-long study. At-home polysomnographic recordings were obtained on successive pairs of nights once per week for a total of eight recordings (nights 1, 2, 8, 9, 15, 16, 22, 23). Subjects (N=54) received placebo pellets on night 8 (single-blind) and verum pellets on night 22 (double-blind) in 30c doses of one of two homeopathic remedies, Nux Vomica or Coffea Cruda. Subjects completed daily morning sleep diaries and weekly Pittsburgh Sleep Quality Index scales, as well as Profile of Mood States Scales at bedtime on polysomnography nights.

Results

Verum remedies significantly increased PSG total sleep time and NREM, as well as awakenings and stage changes. Changes in actigraphic and self-rated scale effects were not significant.

Conclusions

The study demonstrated the feasibility of using in-home all-night sleep recordings to study homeopathic remedy effects. Findings are similar though not identical to those reported in animals with the same remedies. Possible mechanisms include initial disruption of the nonlinear dynamics of sleep patterns by the verum remedies.

Abstract

Background

There are widespread assumptions that a large proportion of American adults use a variety of complementary and alternative medicine (CAM) therapies. The goal of this study is to explore the clustering or linkages among CAM categories in the general population. Linkset analysis and data from the 2002 National Health Interview Survey (NHIS) were used to address two specific aims. First, the dominant linkages of CAM categories used by the same individual were delineated, and population estimates were generated of the percentage of American adults using different linksets of CAM categories. Second, it was determined whether dominant linkages of CAM modalities differ by age, gender, ethnicity, and education.

Methods

Linkset analysis, a method of estimating co-occurrence beyond chance, was used on data from the 2002 NHIS (N = 29,862) to identify possible sets of CAM use.

Results

Most adults use CAM therapies from a single category. Approximately 20% of adults combined two CAM categories, with the combination of mind–body therapies and biologically based therapies estimated to be most common. Only 5% of adults use therapies representing three or more CAM categories. Combining therapies across multiple CAM categories was more common among those 46–64, women, whites, and those with a college education.

Conclusions

The results of this study allow researchers to refine descriptions of CAM use in the adult population. Most adults do not use a wide assortment of CAM; most use therapies within a single CAM category. Sets of CAM use were found to differ by age, gender, ethnicity, and education in ways consistent with previous research.

Objectives

The purpose of this study was to prospectively examine the relationship between anemia and incident fractures of the hip, spine and all skeletal sites in women from diverse racial and ethnic backgrounds enrolled in the Women's Health Initiative (WHI) Observational Study and Clinical Trials.

Design

Prospective cohort study.

Setting

40 WHI clinical centers across the US.

Participants

Postmenopausal women (n = 160,080), mean age 63.2 (SD: 7.2) years, were recruited and followed for an average of 7.8 years.

Measurements

Anemia was defined as hemoglobin levels at baseline less than 12 g/dL. All fractures were self-reported. Hip fractures were further confirmed by trained physicians using medical records.

Results

Among the participants 8,739 women (5.5%) were anemic. The age-adjusted incidence rate of hip fractures per 10,000 person years were 21.4 in women with anemia and 15.0 in women without anemia; a higher incidence rate for spine or all fractures in anemic women was also observed. After multiple covariates were included in the Cox proportional hazards models, significant increased fracture risk associated with anemia still existed as demonstrated by the hazards ratios (95% confidence interval) of fractures associated with anemia being 1.38 (1.13–1.68), 1.30 (1.09–1.55) and 1.07 (1.01–1.14) for hip, spine and all-types respectively. No significant racial/ethnic difference was found in these relationships.

Conclusion

A significantly increased fracture risk was observed in multi-ethnic postmenopausal women with anemia. Given the high prevalence of anemia in the elderly population, it is important to better understand the relationship and mechanisms linking anemia to fracture risk.

Background

Substantial recent research examines the efficacy of many types of complementary and alternative (CAM) therapies. However, outcomes associated with the "real-world" use of CAM has been largely overlooked, despite calls for CAM therapies to be studied in the manner in which they are practiced. Americans seek CAM treatments far more often for chronic musculoskeletal pain (CMP) than for any other condition. Among CAM treatments for CMP, acupuncture and chiropractic (A/C) care are among those with the highest acceptance by physician groups and the best evidence to support their use. Further, recent alarming increases in delivery of opioid treatment and surgical interventions for chronic pain--despite their high costs, potential adverse effects, and modest efficacy--suggests the need to evaluate real world outcomes associated with promising non-pharmacological/non-surgical CAM treatments for CMP, which are often well accepted by patients and increasingly used in the community.

Methods/Design

This multi-phase, mixed methods study will: (1) conduct a retrospective study using information from electronic medical records (EMRs) of a large HMO to identify unique clusters of patients with CMP (e.g., those with differing demographics, histories of pain condition, use of allopathic and CAM health services, and comorbidity profiles) that may be associated with different propensities for A/C utilization and/or differential outcomes associated with such care; (2) use qualitative interviews to explore allopathic providers' recommendations for A/C and patients' decisions to pursue and retain CAM care; and (3) prospectively evaluate health services/costs and broader clinical and functional outcomes associated with the receipt of A/C relative to carefully matched comparison participants receiving traditional CMP services. Sensitivity analyses will compare methods relying solely on EMR-derived data versus analyses supplementing EMR data with conventionally collected patient and clinician data.

Discussion

Successful completion of these aggregate aims will provide an evaluation of outcomes associated with the real-world use of A/C services. The trio of retrospective, qualitative, and prospective study will also provide a clearer understanding of the decision-making processes behind the use of A/C for CMP and a transportable methodology that can be applied to other health care settings, CAM treatments, and clinical populations.

Trial registration

ClinicalTrials.gov: NCT01345409

Objective

The purpose of this paper is to present a preliminary model to identify the effects of expectancy of treatment success and the patient-provider encounter (PPE) on outcomes in an open-label randomized trial.

Methods

80 participants with chronic cervicogenic headache (CGH) were randomized to 4 groups: 2 levels of treatment dose (8 or 16) and 2 levels of therapy from a chiropractor (spinal manipulation or light massage). Providers were instructed to have equal enthusiasm for all care. Structural equation modeling with standardized path coefficients (β) was used in a path analysis to identify the effects of patient expectancy and the PPE on CGH pain. The model included monthly pain from baseline to 12 weeks. Expectancy and PPE were evaluated on Likert scales. The PPE was measured as patient perception of chiropractor enthusiasm, confidence, and comfort with care.

Results

Baseline patient expectancy was balanced across groups. PPE measures were balanced across groups and consistent over the 8-week treatment period. Treatment and baseline pain had the strongest effects on pain outcomes (|β| =.46 to .59). Expectations had little effect on pain (|β| < .15). The PPE had a weak effect on pain (|β| = .03 to .27) and on subsequent confidence in treatment success (|β| = .09 and .12).

Conclusions

Encouraging equipoise in the provider-patient encounter and balancing expectancy across treatment groups may protect against some confounding related to the absence of blinding in a randomized controlled trial of pain. In this trial, their effects were found to be small relative to the effects of treatment and baseline values.

The present study describes the development of a comprehensive quality of reporting assessment tool and its application to acupuncture RCTs from 1997–2007. This Oregon CONSORT STRICTA Instrument (OCSI) is based on the revised CONSORT guidelines as modified by the STRICTA recommendations for acupuncture trials. Each of the resulting 27 OCSI items were applied to English language prospective RCTs that compared acupuncture, using manual and/or electro-stimulation, to no treatment, a sham procedure, or usual biomedical care. The 333 RCTs that met inclusion criteria were dispersed among 27 countries and 141 journals. Mean quality of reporting score for all articles was 63.0% (SD 16.5). Mean OCSI scores revealed a 30.9% improvement over the ten-year period (P < .001). Our findings suggest that to enhance quality of reporting, authors should better attend to seven specific OCSI items in three categories: practitioner training, adverse events, and aspects of randomization and blinding (n = 5). The broad diversity in geographical origin, publication site and quality of reporting, viewed in light of the considerable room for improvement in mean OCSI scores, emphasizes the importance of making STRICTA as well as CONSORT more widely known to journals and to the acupuncture research community.

Background

The Gail model has been commonly used to estimate a woman’s breast cancer risk in a certain time period. High bone mineral density (BMD) is also a significant risk factor for breast cancer, but it plays no role in the Gail model. The objective of this study was to investigate whether hip BMD predicts postmenopausal breast cancer risk independently of the Gail score.

Methods

In this prospective study, postmenopausal women (N = 9,941) who had baseline hip BMD and Gail score from the Women’s Health Initiative were included in the analysis. Their average age was 63.0 ± 7.4 years at baseline.

Results

After an average of 8.43-years of follow-up, 327 incident breast cancer cases were reported and adjudicated. In a multivariate Cox proportional hazards model, the hazard ratios (95%CI) for incident breast cancer were 1.35 (1.05–1.73) for high Gail score (≥1.67%), and 1.25 (1.11–1.40) for each unit of increase in total hip BMD T-score. Restricting the analysis to women with both BMD and Gail score above the median, a sharp increase in incident breast cancer for women with the highest BMD and Gail scores was found (p<0.05).

Conclusions

The contribution of BMD to the prediction of incident postmenopausal breast cancer across the entire population is independent from Gail score. However, among women with both high BMD and high Gail score there appears to be an interaction between these two factors. These findings suggest that BMD and Gail score may be used together to better quantify risk of breast cancer.

Abstract

Objective

To investigate whether a training process that focused on a questionnaire-based diagnosis in Traditional Chinese Medicine (TCM), and developing diagnostic consensus, would improve the agreement of TCM diagnoses among 10 TCM practitioners evaluating patients with temporomandibular joint disorder (TMJD).

Design and setting

Evaluation of a diagnostic training program at the Department of Family and Community Medicine, University of Arizona, Tucson Arizona, and the Oregon College of Oriental Medicine, Portland, Oregon.

Subjects

Screened participants for a study of TCM for TMJD.

Practitioners

Ten (10) licensed acupuncturists with a minimum of 5 years licensure and education in Chinese herbs.

Methods

A training session using a questionnaire-based diagnostic form was conducted, followed by waves of diagnostic sessions. Between sessions, practitioners discussed the results of the previous round of participants with a focus on reducing variability in primary diagnosis and severity rating of each diagnosis: 3 waves of 5 patients were assessed by 4 practitioner pairs for a total of 120 diagnoses. At 18 months, practitioners completed a recalibration exercise with a similar format with a total of 32 diagnoses. These diagnoses were then examined with respect to the rate of agreement among the 10 practitioners using inter-rater correlations and kappas.

Results

The inter-rater correlation with respect to the TCM diagnoses among the 10 practitioners increased from 0.112 to 0.618 with training. Statistically significant improvements were found between the baseline and 18 month exercises (p < 0.01).

Conclusions

Inter-rater reliability of TCM diagnosis may be improved through a training process and a questionnaire-based diagnosis process. The improvements varied by diagnosis, with the greatest congruence among primary and more severe diagnoses. Future TCM studies should consider including calibration training to improve the validity of results.

Objective This article describes website use and behavioral outcomes in a multi-component lifestyle intervention promoting healthy diet and exercise. Methods A 2-year randomized clinical trial to improve bone density in 228 adolescent girls, the intervention included a website designed to enhance intervention adherence, retention of participants, and behavioral outcomes. Measures included diet and exercise recalls, surveys, and web-usage data. Results Website use was associated with increases in calcium intake (ß = 69.72, p =.01, ES = 0.15) and high-impact activity (ß = 10.93, p =.04, ES =.13). Use of web pages related to behavioral feedback and communications was not significantly associated with behavioral outcomes. The most visited website pages had content related to incentive points, caption contests, and fun facts. Conclusions Web elements of a multi-component intervention may promote retention and engagement in target behaviors. Such websites may be most acceptable to adolescent participants if they blend fun and behavioral elements, rather than exclusively focusing on behavioral changes.

Dynamic allocation of participants to treatments in a clinical trial has been an alternative to randomization for nearly 35 years. Design-adaptive allocation is a particularly flexible kind of dynamic allocation. Every investigation of dynamic allocation methods has shown that they improve balance of prognostic factors across treatment groups, but there have been lingering doubts about their influence on the validity of statistical inferences. Here we report the results of a simulation study focused on this and similar issues. Overall, it is found that there are no statistical reasons, in the situations studied, to prefer randomization to design-adaptive allocation. Specifically, there is no evidence of bias, the number of participants wasted by randomization in small studies is not trivial, and when the aim is to place bounds on the prediction of population benefits, randomization is quite substantially less efficient than design-adaptive allocation. A new, adjusted permutation estimate of the standard deviation of the regression estimator under design-adaptive allocation is shown to be an unbiased estimate of the true sampling standard deviation, resolving a long-standing problem with dynamic allocations. These results are shown in situations with varying numbers of balancing factors, different treatment and covariate effects, different covariate distributions, and in the presence of a small number of outliers.

Objective

To examine associations among life events stress, social support, and breast cancer incidence in a cohort of postmenopausal women.

Design and main outcome measure

Women’s Health Initiative observational study participants, breast cancer free at entry, who provided assessment of stressful life events, social support, and breast cancer risk factors, were prospectively followed for breast cancer incidence (n=84,334).

Results

During an average of 7.6 years of follow-up, 2,481 invasive breast cancers were diagnosed. In age-adjusted proportional hazards models, one stressful life event was associated with increased risk, but risk decreased with each additional stressful life event. After adjustment for confounders the decreasing risk was not significant. Stressful life events and social support appeared to interact in relation to breast cancer risk such that women who had greater number of stressful life events and low social support had a decreased risk of breast cancer.

Conclusions

This study found no independent association between stressful life events and breast cancer risk. The results are compatible with a more complex model of psychosocial factors interacting in relation to breast cancer risk.

Objectives

To assess the feasibility and acceptability of studying whole systems of Traditional Chinese Medicine (TCM) and Naturopathic medicine (NM) in the treatment of temporomandibular disorders (TMD), and to determine whether there is indication to support further research.

Design

A pilot study using a randomized controlled clinical trial design of whole system TCM and NM versus state-of-the-art specialty care (SC).

Setting/location

Kaiser Permanente Northwest (KPNW), and practitioner offices in Portland, Oregon.

Subjects

One hundred and sixty (160) women 25–55 years of age attending a KPNW TMD specialty clinic.

Interventions

Whole system TCM and NM, and KPNW TMD clinic SC; the intervention protocols were designed to model the individually tailored type of community care offered in alternative medicine practices in Portland and in the KPNW TMD clinic, using protocols that enhanced similarities among practitioners within each system and permitted full descriptions of the treatments provided.

Outcome measures

TMD was ascertained using the Research Diagnostic Criteria/TMD; outcomes were self-reported worst and average facial pain and interference with activities (scaled 0–10 where 10 is worst).

Results

Of 948 consecutive eligible patients, 160 were randomized to one of three arms; 128 provided endpoint data. TCM and NM demonstrated significantly greater in-treatment reductions for worst facial pain compared to SC (adjusted regression analysis; higher negative values indicate greater improvement, = −1.11 ± 0.43, p = 0.010 and −1.02 ± 0.45, p = 0.025 for TCM and NM, respectively, compared to SC) and at 3 months post-treatment (−1.07 ± 0.51, p = 0.037 and −1.27 ± 0.54, p = 0.019 for TCM and NM versus SC, respectively). Additionally, TCM provided significantly greater decreases in average pain than SC; NM provided significantly greater decreases than SC or TCM in TMD-related psychosocial interference.

Conclusions

These alternative medicine approaches each resulted in significantly greater reduction of pain and psychosocial interference than SC. Further research on the potential benefits of traditional whole systems of medicine for TMD appears warranted.

Abstract

Objectives

To assess the feasibility and acceptability of studying whole systems of Traditional Chinese Medicine (TCM) and Naturopathic medicine (NM) in the treatment of temporomandibular disorders (TMD), and to determine whether there is indication to support further research.

Design

A pilot study using a randomized controlled clinical trial design of whole system TCM and NM versus state-of-the-art specialty care (SC).

Setting/location

Kaiser Permanente Northwest (KPNW), and practitioner offices in Portland, Oregon.

Subjects

One hundred and sixty (160) women 25–55 years of age attending a KPNW TMD specialty clinic.

Interventions

Whole system TCM and NM, and KPNW TMD clinic SC; the intervention protocols were designed to model the individually tailored type of community care offered in alternative medicine practices in Portland and in the KPNW TMD clinic, using protocols that enhanced similarities among practitioners within each system and permitted full descriptions of the treatments provided.

Outcome measures

TMD was ascertained using the Research Diagnostic Criteria/TMD; outcomes were self-reported worst and average facial pain and interference with activities (scaled 0–10 where 10 is worst).

Results

Of 948 consecutive eligible patients, 160 were randomized to one of three arms; 128 provided endpoint data. TCM and NM demonstrated significantly greater in-treatment reductions for worst facial pain compared to SC (adjusted regression analysis; higher negative values indicate greater improvement, = −1.11 ± 0.43, p = 0.010 and −1.02 ± 0.45, p = 0.025 for TCM and NM, respectively, compared to SC) and at 3 months post-treatment (−1.07 ± 0.51, p = 0.037 and −1.27 ± 0.54, p = 0.019 for TCM and NM versus SC, respectively). Additionally, TCM provided significantly greater decreases in average pain than SC; NM provided significantly greater decreases than SC or TCM in TMD-related psychosocial interference.

Conclusions

These alternative medicine approaches each resulted in significantly greater reduction of pain and psychosocial interference than SC. Further research on the potential benefits of traditional whole systems of medicine for TMD appears warranted.