Do we want more cancer patients on clinical trials If so, what are the barriers to greater accrual

It is often stated that only a small proportion of adult cancer patients participate in clinical trials. This is said to be a bad thing, with calls for more trials to include more patients. Here I argue that whether or not greater accrual to clinical trials would be a good thing depends on the trials we conduct. The vast majority of clinical trials in cancer are currently early phase trials, and most do not lead to further studies even if they have encouraging results. The key metric is thus not the number of patients on clinical trials, but the number on the sort of large, randomized, Phase III trials that can be used as a basis for clinical decisions. I also address two important barriers to greater clinical trial participation. The first barrier is financial: clinical research has long been the poor cousin of basic research, with perhaps no more than a nickel in the cancer research dollar going to clinical research. The second barrier is regulatory: clinical research has become so overburdened by regulation that it takes years to initiate a trial, and dedicated staff just to deal with the paperwork once the trial starts. This not only adds significantly to the costs of clinical research, but scares many young investigators away. It has been estimated that nearly half of all US-sponsored trials are being conducted abroad, and it is plausible that excessive regulation is at least partly responsible. That statistic should serve as a wake-up call to the US clinical research community to implement the recommendations of the now decade-old report of National Cancer Institute Clinical Trials Program Review Group, which largely center around simplifying trials and streamlining trial procedures

Systematic reviews of complementary therapies - an annotated bibliography. Part 1: Acupuncture

Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with acupuncture. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of acupuncture; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. Results From a total of 48 potentially relevant reviews preselected in a screeening process 39 met the inclusion criteria. 22 were on various pain syndromes or rheumatic diseases. Other topics addressed by more than one review were addiction, nausea, asthma and tinnitus. Almost unanimously the reviews state that acupuncture trials include too few patients. Often included trials are heterogeneous regarding patients, interventions and outcome measures, are considered to have insufficient quality and contradictory results. Convincing evidence is available only for postoperative nausea, for which acupuncture appears to be of benefit, and smoking cessation, where acupuncture is no more effective than sham acupuncture. Conclusions A large number of systematic reviews on acupuncture exists. What is most obvious from these reviews is the need for (the funding of) well-designed, larger clinical trials

Method for evaluating prediction models that apply the results of randomized trials to individual patients

<p>Abstract</p> <p>Introduction</p> <p>The clinical significance of a treatment effect demonstrated in a randomized trial is typically assessed by reference to differences in event rates at the group level. An alternative is to make individualized predictions for each patient based on a prediction model. This approach is growing in popularity, particularly for cancer. Despite its intuitive advantages, it remains plausible that some prediction models may do more harm than good. Here we present a novel method for determining whether predictions from a model should be used to apply the results of a randomized trial to individual patients, as opposed to using group level results.</p> <p>Methods</p> <p>We propose applying the prediction model to a data set from a randomized trial and examining the results of patients for whom the treatment arm recommended by a prediction model is congruent with allocation. These results are compared with the strategy of treating all patients through use of a net benefit function that incorporates both the number of patients treated and the outcome. We examined models developed using data sets regarding adjuvant chemotherapy for colorectal cancer and Dutasteride for benign prostatic hypertrophy.</p> <p>Results</p> <p>For adjuvant chemotherapy, we found that patients who would opt for chemotherapy even for small risk reductions, and, conversely, those who would require a very large risk reduction, would on average be harmed by using a prediction model; those with intermediate preferences would on average benefit by allowing such information to help their decision making. Use of prediction could, at worst, lead to the equivalent of an additional death or recurrence per 143 patients; at best it could lead to the equivalent of a reduction in the number of treatments of 25% without an increase in event rates. In the Dutasteride case, where the average benefit of treatment is more modest, there is a small benefit of prediction modelling, equivalent to a reduction of one event for every 100 patients given an individualized prediction.</p> <p>Conclusion</p> <p>The size of the benefit associated with appropriate clinical implementation of a good prediction model is sufficient to warrant development of further models. However, care is advised in the implementation of prediction modelling, especially for patients who would opt for treatment even if it was of relatively little benefit.</p

Concurrent use of prescription drugs and herbal medicinal products in older adults: A systematic review

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The use of herbal medicinal products (HMPs) is common among older adults. However, little is known about concurrent use with prescription drugs as well as the potential interactions associated with such combinations. Objective Identify and evaluate the literature on concurrent prescription and HMPs use among older adults to assess prevalence, patterns, potential interactions and factors associated with this use. Methods Systematic searches in MEDLINE, PsycINFO, EMBASE, CINAHL, AMED, Web of Science and Cochrane from inception to May 2017 for studies reporting concurrent use of prescription medicines with HMPs in adults (≥65 years). Quality was assessed using the Joanna Briggs Institute checklists. The Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) three stage approach to mixed method research was used to synthesise data. Results Twenty-two studies were included. A definition of HMPs or what was considered HMP was frequently missing. Prevalence of concurrent use by older adults varied widely between 5.3% and 88.3%. Prescription medicines most combined with HMPs were antihypertensive drugs, beta blockers, diuretics, antihyperlipidemic agents, anticoagulants, analgesics, antihistamines, antidiabetics, antidepressants and statins. The HMPs most frequently used were: ginkgo, garlic, ginseng, St John’s wort, Echinacea, saw palmetto, evening primrose oil and ginger. Potential risks of bleeding due to use of ginkgo, garlic or ginseng with aspirin or warfarin was the most reported herb-drug interaction. Some data suggests being female, a lower household income and less than high school education were associated with concurrent use. Conclusion Prevalence of concurrent prescription drugs and HMPs use among older adults is substantial and potential interactions have been reported. Knowledge of the extent and manner in which older adults combine prescription drugs will aid healthcare professionals can appropriately identify and manage patients at risk.Peer reviewedFinal Published versio

Cost-effectiveness of adjunct non-pharmacological interventions for osteoarthritis of the knee

BACKGROUND: There is limited information on the costs and benefits of alternative adjunct non-pharmacological treatments for knee osteoarthritis and little guidance on which should be prioritised for commissioning within the NHS. This study estimates the costs and benefits of acupuncture, braces, heat treatment, insoles, interferential therapy, laser/light therapy, manual therapy, neuromuscular electrical stimulation, pulsed electrical stimulation, pulsed electromagnetic fields, static magnets and transcutaneous electrical nerve Stimulation (TENS), based on all relevant data, to facilitate a more complete assessment of value. METHODS: Data from 88 randomised controlled trials including 7,507 patients were obtained from a systematic review. The studies reported a wide range of outcomes. These were converted into EQ-5D index values using prediction models, and synthesised using network meta-analysis. Analyses were conducted including firstly all trials and secondly only trials with low risk of selection bias. Resource use was estimated from trials, expert opinion and the literature. A decision analytic model synthesised all evidence to assess interventions over a typical treatment period (constant benefit over eight weeks or linear increase in effect over weeks zero to eight and dissipation over weeks eight to 16). RESULTS: When all trials are considered, TENS is cost-effective at thresholds of £20-30,000 per QALY with an incremental cost-effectiveness ratio of £2,690 per QALY vs. usual care. When trials with a low risk of selection bias are considered, acupuncture is cost-effective with an incremental cost-effectiveness ratio of £13,502 per QALY vs. TENS. The results of the analysis were sensitive to varying the intensity, with which interventions were delivered, and the magnitude and duration of intervention effects on EQ-5D. CONCLUSIONS: Using the £20,000 per QALY NICE threshold results in TENS being cost-effective if all trials are considered. If only higher quality trials are considered, acupuncture is cost-effective at this threshold, and thresholds down to £14,000 per QALY

An Analysis of News Media Coverage of Complementary and Alternative Medicine

Background: To examine the accuracy and adequacy of lay media news stories about complementary and alternative medicines and therapies. Methodol./Principal Findings: A descriptive anal. of news stories about complementary and alternative medicine (CAM) in the Australian media using a national medical news monitoring website, mediadoctor.org.au. Each story was rated against 10 criteria by two individuals. Consensus scores of 222 news articles reporting therapeutic claims about complementary medicines posted on mediadoctor.org.au between 1 Jan. 2004 and 1 Sept. 2007 were calculated. The overall rating score for 222 CAM articles was 50% (95% CI 47% to 53%). There was a statistically significant (F = 3.68, p = 0.006) difference in cumulative mean scores according to type of therapy: biol. based practices (54%, 95% CI 50% to 58%); manipulative body based practices (46%, 95% CI 39% to 54%), whole medical systems (45%, 95% CI 32% to 58%), mind body medicine (41%, 95% CI 31% to 50%) and energy medicine (33%, 95% CI 11% to 55%). There was a statistically significant difference in cumulative mean scores (F = 3.72, p = 0.0001) according to the clin. outcome of interest with stories about cancer treatments (62%, 95% CI 54% to 70%) scoring highest and stories about treatments for children's behavioral and mental health concerns scoring lowest (31%, 95% CI 19% to 43%). Significant differences were also found in scores between media outlets. Conclusions/Significance: There is substantial variability in news reporting practices about CAM. Overall, although they may be improving, the scores remain generally low. It appears that much of the information the public receives about CAM is inaccurate or incomplete

Offspring of Mothers Fed a High Fat Diet Display Hepatic Cell Cycle Inhibition and Associated Changes in Gene Expression and DNA Methylation

The association between an adverse early life environment and increased susceptibility to later-life metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease is described by the developmental origins of health and disease hypothesis. Employing a rat model of maternal high fat (MHF) nutrition, we recently reported that offspring born to MHF mothers are small at birth and develop a postnatal phenotype that closely resembles that of the human metabolic syndrome. Livers of offspring born to MHF mothers also display a fatty phenotype reflecting hepatic steatosis and characteristics of non-alcoholic fatty liver disease. In the present study we hypothesised that a MHF diet leads to altered regulation of liver development in offspring; a derangement that may be detectable during early postnatal life. Livers were collected at postnatal days 2 (P2) and 27 (P27) from male offspring of control and MHF mothers (n = 8 per group). Cell cycle dynamics, measured by flow cytometry, revealed significant G0/G1 arrest in the livers of P2 offspring born to MHF mothers, associated with an increased expression of the hepatic cell cycle inhibitor Cdkn1a. In P2 livers, Cdkn1a was hypomethylated at specific CpG dinucleotides and first exon in offspring of MHF mothers and was shown to correlate with a demonstrable increase in mRNA expression levels. These modifications at P2 preceded observable reductions in liver weight and liver∶brain weight ratio at P27, but there were no persistent changes in cell cycle dynamics or DNA methylation in MHF offspring at this time. Since Cdkn1a up-regulation has been associated with hepatocyte growth in pathologic states, our data may be suggestive of early hepatic dysfunction in neonates born to high fat fed mothers. It is likely that these offspring are predisposed to long-term hepatic dysfunction

Academic doctors' views of complementary and alternative medicine (CAM) and its role within the NHS: an exploratory qualitative study

<p>Abstract</p> <p>Background</p> <p>There has been a marked increase in the use of complementary and alternative medicine (CAM) in the UK population in recent years. Surveys of doctors' perspectives on CAM have identified a variety of views and potential information needs. While these are useful for describing the proportions of doctors who hold particular attitudes towards CAM, they are less helpful for understanding why. In addition, while the views of non-academic doctors have begun to be studied, the perspective and rationales of academic doctors remains under-researched. It seems important to investigate the views of those with a research-orientation, given the emphasis on the need for more scientific evidence in recent debates on CAM.</p> <p>Methods</p> <p>This exploratory study used qualitative methods to explore academic doctors' views of CAM and the rationales they provided for their views. A purposeful sampling strategy was used to identify doctors with a dual clinical and academic role in the Bristol area, with an anticipated variety of views on CAM. Semi-structured interviews were conducted with nine doctors. The data were analysed thematically, drawing on the Framework Approach.</p> <p>Results</p> <p>The doctors expressed a spectrum of views on CAM, falling into three broad groups: the 'enthusiasts', the 'sceptics' and the 'undecided'. Scepticism or uncertainty about the value of CAM was prominent, except among those practising a form of CAM. A variety of rationales underpinned their perspectives on CAM, a key recurring rationale being their perspective on the scientific evidence base. The main themes arising included: the role of doctors' professional experiences of conventional medicine and CAM in shaping their attitudes towards CAM, doctor-patient communication about CAM and patient disclosure, whether there is a need for training and education in CAM for doctors, a hierarchy of acceptability of CAM and the nature of evidence; and the role of CAM within the NHS.</p> <p>Conclusion</p> <p>Despite the caution or scepticism towards CAM expressed by doctors in this study, more open doctor-patient communication about CAM may enable doctors' potential concerns about CAM to be addressed, or at least enhance their knowledge of what treatments or therapies their patients are using. Offering CAM to patients may serve to enhance patients' treatment choices and even increase doctors' fulfilment in their practice. However, given the recurring concerns about lack of scientific evidence expressed by the doctors in this study, perceptions of the evidence base may remain a significant barrier to greater integration of CAM within the NHS.</p

Patients visiting the complementary medicine clinic for pain: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Pain is one of the most common reasons for seeking medical care. The purpose of this study was to characterize patients visiting the complementary medicine clinic for a pain complaint.</p> <p>Methods</p> <p>This is a cross-sectional study. The study took place at Clalit Health Services (CHS) complementary clinic in Beer-Sheva, Israel. Patients visiting the complementary clinic, aged 18 years old and older, Hebrew speakers, with a main complaint of pain were included. Patients were recruited consecutively on random days of the month during a period of six months. Main outcome measures were: pain levels, location of pain, and interference with daily activities. Once informed consent was signed patients were interviewed using a structured questionnaire by a qualified nurse. The questionnaire included socio-demographic data, and the Brief Pain Inventory (BPI).</p> <p>Results</p> <p>Three-hundred and ninety-five patients were seen at the complementary medicine clinic during the study period, 201 (50.8%) of them met the inclusion criteria. Of them, 163 (81.1%) agreed to participate in the study and were interviewed. Pain complaints included: 69 patients (46.6%) with back pain, 65 (43.9%) knee pain, and 28 (32.4%) other limbs pain. Eighty-two patients (50.3%) treated their pain with complementary medicine as a supplement for their conventional treatment, and 55 (33.7%) felt disappointed from the conventional medicine experience. Eighty-three patients (50.9%) claimed that complementary medicine can result in better physical strength, or better mental state 51 (31.3%). Thirty-seven patients (22.7%) were hoping that complementary medicine will prevent invasive procedures.</p> <p>Conclusion</p> <p>Given the high proportion of patients with unsatisfactory pain relief using complementary and alternative medicine (CAM), general practitioners should gain knowledge about CAM and CAM providers should gain training in pain topics to improve communication and counsel patients. More clinical research to evaluate safety and efficiency of CAM for pain is needed to provide evidence based counseling.</p