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Andrew J Vickers

Publications and source records attributed to Andrew J Vickers.

At least 37 records · Page 2Linked to original sources
PubMed2006

How to randomize.

Randomized trials are an important method for deciding whether integrative oncology therapies do more good than harm. Many investigators do not pay sufficient attention to randomization procedures, and several studies have shown that only a fraction of trial reports describe randomization adequately. The purpose of randomization is to prevent selection bias: randomization procedures must therefore ensure that researchers are unable to predict the group to which a patient will be randomized until the patient is unambiguously registered on study; moreover, researchers must be unable to change a patient's allocation after the patients are registered. The use of telephone randomization and opaque envelopes has been suggested as a good randomization method, but both can be subverted. Randomization should be conducted either by a pharmaceutical company, which sends blinded medication to the hospital pharmacy, or by a secure, password-protected database system. Computer randomization can easily incorporate extensions of randomization, such as blocking, stratification, and minimization, which can help ensure balance between groups.

Humans↗
PubMed2006

How to design a phase I trial of an anticancer botanical.

Phase I trials are an important part of traditional drug development in oncology. Such trials address two key issues: safety and dose. Currently, there is a dearth of phase I trials of anticancer botanicals. This may result from the apparently widespread view that a history of human use precludes the need for early-phase study. However, the safe use of a botanical by the population at large does not guarantee safety when the botanical is used in combination with other agents in the complex medical setting of oncology. Several cases of unpredictable adverse events have been recorded following the use of botanicals by cancer patients. We propose a simple, robust design for phase I trials of anticancer botanicals. This design incorporates important characteristics of botanical medicines including low toxicity, prior data on a likely safe dose, a limit on the highest dose it is feasible to administer, and the unknown relationship between dose-toxicity and dose-response curves. Two principal design features are the use of predetermined dose levels and the direct measurement of a response endpoint such as survival or immunity. This response end point can be used to determine the optimal dose if toxicity is acceptable at all dose levels. Increasing the use of phase I methodology would ensure a more systematic development of botanicals as anticancer agents. This would likely increase the chance that at least one such agent would be proven to extend lives.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Parametric versus non-parametric statistics in the analysis of randomized trials with non-normally distributed data.

BACKGROUND: It has generally been argued that parametric statistics should not be applied to data with non-normal distributions. Empirical research has demonstrated that Mann-Whitney generally has greater power than the t-test unless data are sampled from the normal. In the case of randomized trials, we are typically interested in how an endpoint, such as blood pressure or pain, changes following treatment. Such trials should be analyzed using ANCOVA, rather than t-test. The objectives of this study were: a) to compare the relative power of Mann-Whitney and ANCOVA; b) to determine whether ANCOVA provides an unbiased estimate for the difference between groups; c) to investigate the distribution of change scores between repeat assessments of a non-normally distributed variable. METHODS: Polynomials were developed to simulate five archetypal non-normal distributions for baseline and post-treatment scores in a randomized trial. Simulation studies compared the power of Mann-Whitney and ANCOVA for analyzing each distribution, varying sample size, correlation and type of treatment effect (ratio or shift). RESULTS: Change between skewed baseline and post-treatment data tended towards a normal distribution. ANCOVA was generally superior to Mann-Whitney in most situations, especially where log-transformed data were entered into the model. The estimate of the treatment effect from ANCOVA was not importantly biased. CONCLUSION: ANCOVA is the preferred method of analyzing randomized trials with baseline and post-treatment measures. In certain extreme cases, ANCOVA is less powerful than Mann-Whitney. Notably, in these cases, the estimate of treatment effect provided by ANCOVA is of questionable interpretability.

Analysis of Variance↗
PubMed2005

Acupuncture for dyspnea in advanced cancer: a randomized, placebo-controlled pilot trial [ISRCTN89462491].

BACKGROUND: Dyspnea, or shortness of breath, is a common symptom in patients with advanced cancer. Pharmacologic management is of proven benefit, but it does not help all patients. Preliminary data suggest that acupuncture can relieve dyspnea in a variety of populations, including cancer patients. We conducted a pilot study (ISRCTN89462491) preparatory to a fully powered randomized, placebo-controlled trial to determine whether acupuncture reduces dyspnea in patients with lung or breast cancer. METHODS: The study sample was comprised of forty-seven patients with lung or breast cancer presenting with dyspnea. Patients receiving symptomatic treatments were not excluded as long as no changes in management were planned during the trial. Patients were randomized to receive a single session of true or placebo acupuncture in addition to their existing dyspnea treatments. Semi-permanent acupuncture "studs" were then inserted: patients applied pressure to these studs twice a day to provide ongoing stimulation to acupuncture points. The subjective sensation of dyspnea was assessed with a 0-10 numerical rating scale immediately before and after acupuncture treatment and daily for a week thereafter. RESULTS: All but two of 47 randomized patients provided follow-up data. Dyspnea scores were slightly higher for patients receiving true versus placebo acupuncture, for both the period immediately following acupuncture treatment and for the daily one week follow-up (differences between means of 0.34, 95% C.I. -0.33, 1.02 and 0.56, 95% C.I. -0.39, 1.51). The 95% confidence interval excludes the prespecified minimum clinically significant difference of a 20% greater improvement in dyspnea for patients receiving acupuncture. CONCLUSION: The acupuncture technique used in this trial is unlikely to have effects on dyspnea importantly larger than placebo for patients with advanced cancer.

Journal Article↗
PubMed2005

Anatomy of accessory pudendal arteries in laparoscopic radical prostatectomy.

PURPOSE: The incidence of accessory pudendal arteries (APAs) varies from 4% to 70% depending on the means used to identify them. We provide a detailed laparoscopic anatomical description of their appearance, location and identification rate based on our series of radical prostatectomies. MATERIALS AND METHODS: The distribution of APAs was prospectively recorded in 285 consecutive patients between October 2002 and November 2004. We defined an APA as any artery located within the periprostatic region running parallel to the dorsal vascular complex and extending caudal toward the anterior perineum, other than cavernous arteries, corona mortis and satellite arteries to the superficial and deep vascular complex. RESULTS: We identified 92 APAs in 72 of 285 patients (25%). Two distinct varieties of APAs were identified. In 10% of patients an APA coursed along the lateral aspect of the prostate, termed lateral APA, and in 13% an APA emerged through the levator ani fibers near the apical region of the prostate, termed apical APA. Five patients (1.7%) were found to have apical and lateral APAs. CONCLUSIONS: APAs are more frequent than previously reported in the surgical literature. To our knowledge apical APAs have never been reported previously. The visualization and accessibility advantages of laparoscopy may account for a higher intraoperative APA identification rate. Their roles in continence and potency remain to be determined.

Arteries↗
PubMed2004

Acupuncture for postchemotherapy fatigue: a phase II study.

PURPOSE: To determine whether improvement in postchemotherapy fatigue following acupuncture treatment is substantial enough to warrant a controlled trial. PATIENTS AND METHODS: We accrued patients at Memorial Sloan-Kettering Cancer Center who had completed cytotoxic chemotherapy but experienced persisting fatigue. Patients with severe anemia, clinical depression, or Karnofsky performance status score less than 70 were excluded. Thirty-seven patients were registered in two cohorts; 31 provided follow-up data. Patients received acupuncture either twice per week for 4 weeks (25 patients) or once per week for 6 weeks (12 patients). The primary end point was change in score on the Brief Fatigue Inventory between baseline and 2 weeks after the final treatment. A baseline Brief Fatigue Inventory score of four or greater was an eligibility requirement for the trial. RESULTS: Patients had completed cytotoxic chemotherapy an average of more than 2 years previously. Baseline fatigue scores were high, with approximately half of the sample scoring in the "severe" range. Mean improvement following acupuncture was 31.1% (95% CI, 20.6% to 41.5%), meeting our prespecified criterion for declaring acupuncture worthy of further study. Increasing age was associated with poorer response and failure to complete the study. There was no important difference in improvement following once-weekly and twice-weekly treatments. CONCLUSION: Acupuncture is worthy of further study in the treatment of postchemotherapy fatigue.

Acupuncture Therapy↗
PubMed2004

Acupuncture for chronic headache in primary care: large, pragmatic, randomised trial.

OBJECTIVE: To determine the effects of a policy of "use acupuncture" on headache, health status, days off sick, and use of resources in patients with chronic headache compared with a policy of "avoid acupuncture." DESIGN: Randomised, controlled trial. SETTING: General practices in England and Wales. PARTICIPANTS: 401 patients with chronic headache, predominantly migraine. Interventions Patients were randomly allocated to receive up to 12 acupuncture treatments over three months or to a control intervention offering usual care. MAIN OUTCOME MEASURES: Headache score, SF-36 health status, and use of medication were assessed at baseline, three, and 12 months. Use of resources was assessed every three months. RESULTS: Headache score at 12 months, the primary end point, was lower in the acupuncture group (16.2, SD 13.7, n = 161, 34% reduction from baseline) than in controls (22.3, SD 17.0, n = 140, 16% reduction from baseline). The adjusted difference between means is 4.6 (95% confidence interval 2.2 to 7.0; P = 0.0002). This result is robust to sensitivity analysis incorporating imputation for missing data. Patients in the acupuncture group experienced the equivalent of 22 fewer days of headache per year (8 to 38). SF-36 data favoured acupuncture, although differences reached significance only for physical role functioning, energy, and change in health. Compared with controls, patients randomised to acupuncture used 15% less medication (P = 0.02), made 25% fewer visits to general practitioners (P = 0.10), and took 15% fewer days off sick (P = 0.2). CONCLUSIONS: Acupuncture leads to persisting, clinically relevant benefits for primary care patients with chronic headache, particularly migraine. Expansion of NHS acupuncture services should be considered.

Acupuncture Therapy↗
PubMed2004

Cost effectiveness analysis of a randomised trial of acupuncture for chronic headache in primary care.

OBJECTIVE: To evaluate the cost effectiveness of acupuncture in the management of chronic headache. DESIGN: Cost effectiveness analysis of a randomised controlled trial. SETTING: General practices in England and Wales. PARTICIPANTS: 401 patients with chronic headache, predominantly migraine. Interventions Patients were randomly allocated to receive up to 12 acupuncture treatments over three months from appropriately trained physiotherapists, or to usual care alone. MAIN OUTCOME MEASURE: Incremental cost per quality adjusted life year (QALY) gained. RESULTS: Total costs during the one year period of the study were on average higher for the acupuncture group (403 pounds sterling; 768 dollars; 598 euros) than for controls (217 pounds sterling) because of the acupuncture practitioners' costs. The mean health gain from acupuncture during the one year of the trial was 0.021 quality adjusted life years (QALYs), leading to a base case estimate of 9180 pounds sterling per QALY gained. This result was robust to sensitivity analysis. Cost per QALY dropped substantially when the analysis incorporated likely QALY differences for the years after the trial. CONCLUSIONS: Acupuncture for chronic headache improves health related quality of life at a small additional cost; it is relatively cost effective compared with a number of other interventions provided by the NHS.

Acupuncture Therapy↗
PubMed2004

Massage therapy for symptom control: outcome study at a major cancer center.

Massage is increasingly applied to relieve symptoms in patients with cancer. This practice is supported by evidence from small randomized trials. No study has examined massage therapy outcome in a large group of patients. At Memorial Sloan-Kettering Cancer Center, patients report symptom severity pre- and post-massage therapy using 0-10 rating scales of pain, fatigue, stress/anxiety, nausea, depression and "other." Changes in symptom scores and the modifying effects of patient status (in- or outpatient) and type of massage were analyzed. Over a three-year period, 1,290 patients were treated. Symptom scores were reduced by approximately 50%, even for patients reporting high baseline scores. Outpatients improved about 10% more than inpatients. Benefits persisted, with outpatients experiencing no return toward baseline scores throughout the duration of 48-hour follow-up. These data indicate that massage therapy is associated with substantive improvement in cancer patients' symptom scores.

Anxiety↗
PubMed2004

Overexpression of c-MYC promotes an undifferentiated phenotype in cultured astrocytes and allows elevated Ras and Akt signaling to induce gliomas from GFAP-expressing cells in mice.

The c-MYC protooncogene is overexpressed in the most malignant primary brain tumor, glioblastoma multiforme (GBM), and has been correlated with the undifferentiated character of several cell types. However, the role of Myc activity in the generation of GBMs is not known. In this report, we show that gene transfer of c-MYC to GFAP-expressing astrocytes in vitro promotes the outgrowth of GFAP-negative, nestin-expressing cells with progenitor-like morphology, growth characteristics and gene-expression pattern. In addition, gene transfer of c-MYC to GFAP-expressing astrocytes in vivo induces GBMs when co-expressed with activated Ras and Akt. Without c-MYC, Ras+Akt induces GBMs from nestin-expressing CNS progenitors but is insufficient in GFAP-expressing differentiated astrocytes. The ability of Myc activity to enhance the oncogenic effects of Ras+Akt appears to be limited to GFAP-expressing astrocytes because nestin-expressing progenitors show no increase in GBM formation with the addition of MYC to Ras+Akt. These studies indicate that one role of MYC activity in the formation of gliomas might be to either promote or reinforce an undifferentiated phenotype required for glioma cells to respond to the oncogenic effects of elevated Ras and Akt activity.

Journal Article↗
PubMed2004

Statistical considerations for use of composite health-related quality-of-life scores in randomized trials.

BACKGROUND: Quality of life instruments are frequently used as outcomes in randomized trials. Instruments that consist of several subscales present researchers with a choice of whether to combine some or all scales into a single composite score. There may be several clinically and scientifically reasonable alternative combinations of subscales for the primary outcome measure. MAJOR FINDINGS: The statistical efficiency of different combinations of subscales depends on the relative effect size of the intervention on each subscale and the correlation between the subscales. Simple equations can be derived for determining the relative statistical efficiency of each clinically reasonable combination of subscales. Hypothetical scenarios show that the number of patients needed in a clinical trial can be twice as great for some combinations of subscales as for others. CONCLUSIONS: There are often compelling clinical or scientific reasons to use a particular subscale or composite in a randomized trial. In the case where a number of different alternatives would be reasonable, statistical efficiency can help guide the choice of endpoint.

Data Interpretation, Statistical↗
PubMed2003

Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: a randomized controlled trial.

BACKGROUND: High-dose therapy with autologous stem cell transplantation (HDT/ASCT) is a commonly used treatment for hematologic malignancies. The procedure causes significant psychological distress and no interventions have been demonstrated to improve mood in these patients. Music therapy has been shown to improve anxiety in a variety of acute medical settings. In the current study, the authors determined the effects of music therapy compared with standard care on mood during inpatient stays for HDT/ASCT. METHODS: Patients with hematologic malignancy admitted for HDT/ASCT at two sites (Memorial Sloan-Kettering Cancer Center and Ireland Cancer Center in Cleveland, Ohio) were randomized to receive music therapy given by trained music therapists or standard care. Outcome was assessed at baseline and every 3 days after randomization using the Profile of Mood States. RESULTS: Of 69 patients registered in the study, follow-up data were available for 62 (90%). During their inpatient stay, patients in the music therapy group scored 28% lower on the combined Anxiety/Depression scale (P = 0.065) and 37% lower (P = 0.01) on the total mood disturbance score compared with controls. CONCLUSIONS: Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT.

Amyloidosis↗
PubMed2003

How many repeated measures in repeated measures designs? Statistical issues for comparative trials.

BACKGROUND: In many randomized and non-randomized comparative trials, researchers measure a continuous endpoint repeatedly in order to decrease intra-patient variability and thus increase statistical power. There has been little guidance in the literature as to selecting the optimal number of repeated measures. METHODS: The degree to which adding a further measure increases statistical power can be derived from simple formulae. This "marginal benefit" can be used to inform the optimal number of repeat assessments. RESULTS: Although repeating assessments can have dramatic effects on power, marginal benefit of an additional measure rapidly decreases as the number of measures rises. There is little value in increasing the number of either baseline or post-treatment assessments beyond four, or seven where baseline assessments are taken. An exception is when correlations between measures are low, for instance, episodic conditions such as headache. CONCLUSIONS: The proposed method offers a rational basis for determining the number of repeat measures in repeat measures designs.

Controlled Clinical Trials as Topic↗
PubMed2003

Use of a single global assessment to reduce missing data in a clinical trial with follow-up at one year.

We conducted a randomized controlled trial (ISRCTN96537534) to assess the effects of acupuncture on migraine and chronic tension headache. Patients (n=401) completed a diary of headache severity four times a day for 4 weeks at baseline, immediately following a 3-month treatment period and 1 year after randomization. During the trial, it appeared that dropout might be higher than expected. We therefore obtained a rapid global assessment of headache from participants to aid imputation of missing data. Patients were contacted by telephone and asked to rate current and baseline headache on a 0-10 scale. Use of global assessment reduced the number of patients from whom we obtained no follow-up headache data from 69 (17%) to 24 (6%). Analysis of patients who provided both a diary and a global assessment demonstrated excellent properties of global assessment, with very similar results to the full diary. We therefore used the global assessment to help impute missing 1-year diary scores. Rapid global assessment can be easily implemented in any trial and aids imputation of missing data, though it should not be used instead of more intensive methods of assessment. Further research might usefully examine the value of global assessment for imputation of missing data in a variety of different settings.

Acupuncture↗
PubMed2003

Complementary and alternative therapies.

Patients with prostate cancer increasingly use complementary and alternative therapies. A well-informed oncologist can guide patients to use such treatments to maximize their benefits and reduce the risk of harm. Patients should be dissuaded from using alternative therapies instead of mainstream care to treat cancer. Preliminary evidence suggests that botanical medicines such as PC-SPES may be of benefit, but comparative human trials are yet to be conducted and problems of contamination resolved. Some complementary therapies help reduce symptoms in early-stage prostate cancer, but botanical remedies must be treated with caution because of the possibility of adverse effects and interactions with conventional medicine.

Complementary Therapies↗
PubMed2003

Underpowering in randomized trials reporting a sample size calculation.

OBJECTIVE: The objective of this study was to determine whether standard deviations (SDs) used in sample size calculations are smaller than those found in the resulting study sample, thereby leading to underpowered studies. METHOD: The predicted SD used in the sample size calculation and the actual SD of the study sample were recorded for randomized trials recently published in one of four major journals. RESULTS: Sample SD was greater than predicted SD for 80% of endpoints. About one quarter of trials required five times as many patients as specified in the sample size calculation. CONCLUSION: Trials reporting sample size calculations for continuous endpoints published in the most reputable medical journals are often underpowered. There seems to be insufficient understanding that the SD of a sample of patients is a random variable, associated with imprecision, that cannot easily be extrapolated from one population to another.

Data Interpretation, Statistical↗