John E Williams

Adverse event reporting in randomised controlled trials of neuropathic pain: considerations for future practice.

Summary Improving adverse event reporting and developing standardize methods for collection of data will facilitate comparisons of information across trials of neuropathic pain. ABSTRACT High‐quality information on the potential benefit and harm of a drug is required for patients and clinicians to make informed treatment decisions and to enable cost‐effectiveness modeling to be undertaken. This systematic review describes the collection and reporting of adverse event data as presented in published clinical trials of neuropathic pain for the evaluation of antidepressant or antiepileptic drugs. A total of 74 studies in 16,323 patients published between 1965 and 2012 were identified, of which 43 were published from 2004 onwards. The review found that methods used to collect adverse event data, the frequency of collection, and the selection criteria used by authors for reporting adverse events vary substantially, and these events are often inadequately reported. Consequently, a potential synthesis of valuable harm information across trials is hampered. We make recommendations regarding the reporting of methods used to collect, assess, select, and present adverse event data in publications. Through the Core Outcome Measures in Effectiveness Trials (COMET) initiative, core outcome sets (which include effectiveness and harm) are developed by disease condition. To facilitate data synthesis for adverse events of drug therapies, we suggest that core outcome sets for harms could be developed by therapeutic class (ie, individualized for each class of drug). To improve comparability of information across trials collection methods need to be standardized for patient reports (spontaneous or prompted) and active surveillance (clinical examinations and laboratory tests). Uniform methods for presenting summary information regarding recurrent events, duration and timing of events requires further research.

EAU Guidelines on Pain Management

Pain is the most common symptom of any illness; the physicians therapeutic task is twofold: to discover and treat the cause of pain and the pain itself, whether or not the underlying cause is treatable, to provide relief and reduce the suffering caused by pain. Although we use the term of pain to define all sensations that hurt or are unpleasant, actually two quite different kinds of pain exist. The first (nociceptive) is associated with tissue damage or inflammation, the second (neuropathic) results from a lesion to the peripheral or central nervous systems. Pain can also be divided in acute and chronic. Caregivers are to face pain in two main settings: after surgery and in cancer patients. These tasks require a multidisciplinary team, able to properly assess and treat pain. Postoperative pain is to be treated early and aggressively. Several drug options are available, to be tailored on the surgical procedure and the patient. Pain in cancer patients consists of different aspects: it can be caused by the cancer itself or may be secondary to muscular spasm or cancer treatments. The management involves mainly pharmacotherapy, but also primary treatments as surgery, radiochemotherapy or even antibiotics can provide an adequate relief. Analgesics are to be employed according to an ascending scale, but other options can be combined to improve the outcome when a satisfactory balance between relief and side effects is not achieved; they include invasive techniques, physical and psychological therapy. The mainstay of pain management entails a interdisciplinary cooperation; it requires a full knowledge of the methods of evaluation and treatment of this condition.

Adverse event reporting in randomised trials of neuropathic pain: challenges for clinical usefulness of safety data

Background Monitoring the safety of therapies is of paramount importance in protecting patients from harm and enabling risk-benefit assessment. The recording and reporting of measures of efficacy has received considerable attention and while by no means perfect, has advanced further than the parallel assessment of harm. The stimulus for this study came from a commissioned effectiveness and cost-effectiveness review of treatments for neuropathic pain in patients (the CEAN study) [1]. CEAN noted that the completeness of adverse event (AE) reporting varied between trials and some expert opinion was required where primary data were insufficient for modeling cost-effectiveness. Further, clinicians indicated that trials sometimes failed to provide adequate information for clinical decision-making and informing patients.

The Characteristics and Quality of Randomized Controlled Trials in Neuropathic Pain A Descriptive Study Based on a Systematic Review

Background:Evidence from randomized controlled trials is regarded as the gold standard in clinical research and yet the quality of the conduct and reporting of trials is variable, even post-Consolidated Standards of Reporting Trials. This study arose from a systematic review and cost-effectiveness analysis of treatment for neuropathic pain. The aim was to provide a description of the included trials and investigate trends in study characteristics and measures of quality over time. Methods:The review provided data regarding study characteristics (patients, place, time, drugs, outcomes), methodological factors (sample size calculations, randomization, reporting baseline patient data, withdrawals, intention-to-treat (ITT), and statistical analysis (completeness and correctness of reporting of results, methods of analysis). Results:A total of 131 trials from 1969 to 2007 were included. Of these, 63% were parallel-group designs, the remainder were cross-over; 73% were placebo-controlled. Several trial features increased or improved over time: trial size, quality (using Jadad score), presentation of baseline data by group, reporting of power calculations, use of visual analogue score or numerical rating scale scales to assess pain, completeness of reporting of statistical results, use of modeling to allow for baseline pain scores. The proportion of withdrawals was constant over time with a mean of 14.3%. The proportion of studies stating the analysis as ITT, increased over time, but inspection of papers indicated that the proportion confirmed as ITT was unchanged. Conclusions:There have been a number of improvements regarding the quality and reporting of randomized controlled trials in neuropathic pain, but some failings remain that at best make some results difficult to interpret and at worst lead to bias.

Towards a pain free hospital: an in-depth qualitative analysis of the pain experiences of head and neck cancer patients undergoing radiotherapy

Background: Treatment for head and neck cancer can frequently be a painful experience with implications for patients in terms of quality of life, nutrition and ultimately treatment outcomes. Pain may arise for a number of reasons in this patient group including the influence of localised tissue damage from radiotherapy, the effects of chemotherapeutic agents as well as the disease process itself. Early identification of cancer pain, through screening and early analgesic and pain management are thought to be the most appropriate approaches to the problem. Aim: To explore in-depth, patients’ views of the experience of pain related to radiotherapy for head and neck cancer, within the context of a randomised controlled trial (RCT) of pain screening and intervention. Sample: A purposive sample of head and neck cancer patients undergoing radiotherapy who were participating in a separate RCT of a proactive pain screening intervention. Methods: A qualitative design using one-off, face-to-face, in-depth interviews. Data were inductively analysed for themes using thematic analysis. Data were collected from September 2012 to January 2013. Findings: Eight participants were interviewed. Several issues around pain management arose and the influence of various factors became apparent. Four dominant themes emerged: facets of radiotherapy pain in head and neck cancer, facilitators and barriers to pain management, pain services and finally interdisciplinary working. Conclusion: The specific issues faced by head and neck cancer patients undergoing radiotherapy highlight the need for pain relieving interventions delivered by pain specialists, in tandem with the development of robust self-management strategies. An integrated approach to care is optimal, comprising pain screening at each outpatient encounter, and review by specialists as necessary.

Routine screening for pain combined with a pain treatment protocol in head and neck cancer: A randomised controlled trial

BACKGROUND We compared the effectiveness and cost of a pain screening and treatment program, with usual care in head and neck cancer patients with significant pain. METHODS Patients were screened for the presence of pain and then randomly assigned to either an intervention group, consisting of a pain treatment protocol and an education program, or to usual care. Primary outcome was change in the Pain Severity Index (PSI) over three months. RESULTS We screened 1074 patients of whom 156 were randomized to either intervention or usual care. Mean PSI was reduced over three months in both groups, with no significant difference between the two groups. The Pain Management Index (PMI) at three months, was significantly improved in the intervention group compared with usual care (P<0.001), as was Patient Satisfaction (mean difference in scores was statistically significant: -0.30 [-0.60 to -0.15]). All subjects reported clinically significant levels of anxiety and depression throughout the study. Treatment costs were significantly higher for intervention (mean=£400) compared with usual care (£200), with a low likelihood of being cost-effective. CONCLUSIONS There was no difference in the Pain Severity Index between the two groups. However there were significant improvements in the intervention group in patient satisfaction and PMI. The pain screening process itself was effective. Sufficient benefit was demonstrated as a result of the intervention to allow continued development of pain treatment pathways, rather than allowing pain treatment to be left to nonformalised ad hoc arrangements.

Establishing a Cancer Pain Clinic in a Developing Country: Effect of a Collaborative Link Project with a U.K. Cancer Pain Center

This paper describes a project for the establishment of a cancer pain clinic in a developing country. The project was conducted according to guidelines from the World Health Organization and utilized a link with an existing cancer pain clinic in the UK. The principal methods used for establishing the new pain clinic included: an assessment of barriers to effective cancer pain control, teaching programs for nurses and trainee doctors, educational links with a UK cancer pain clinic, and analgesic guidelines and introduction of a pain assessment tool. As a result of these interventions, a new cancer pain clinic was founded. The methods used serve as one possible model for establishing cancer pain treatment facilities in developing countries.

Data in longitudinal randomised controlled trials in cancer pain: is there any loss of the information available in the data? Results of a systematic literature review and guideline for reporting.

BackgroundGiven the prevalence of untreated pain among cancer patients, there have been calls for more and better research in the domain. Increasingly, calls for less waste and more optimal use of trial data collected are being made. Waste of data includes non-optimal statistical analysis and non-presentation of interpretable effect size as a measure of effectiveness of an intervention which also enable comparisons across studies.MethodsWe reviewed the recent literature on randomised trials on longitudinal cancer pain to identify sources of loss of data information by collecting material on the nature of outcomes collected, analysed, the method of analysis and what was presented as a result of the trial. Illustrated with real data, we propose some guidelines on how to adequately analyse longitudinal data and report the results using mixed models.ResultsWe identified some major source of data information loss, one of which is the transformation of a continuous pain outcome. Not adjusting for the collected outcome baseline value is moreover a source of bias. Multiple testing by analysing the data cross-sectionnally at each time-point leads to loss of information and power. Finally, effect sizes reflecting the effectiveness of the intervention were never reported.ConclusionsWe identified several sources of information loss in the way longitudinal trials on pain were analysed and reported. However these problems could be easily solved by using regression methods like mixed models and presenting regression parameters to provide a concrete quantitative effect of the intervention.

An open pilot study investigating the use of a strong sublingual opioid (phenazocine) for postoperative analgesia

Abstract Phenazocine is a unique opioid as it is a pure μ-agonist and is absorbed sublingually. It is similar to morphine and has a low incidence of sedation, nausea and vomiting and does not cause spasm of the sphincter of Oddi. We have performed an observational pilot study to evaluate the effectiveness of sublingual phenazocine for postoperative pain. Twenty patients were included. All patients were reviewed at 24 hours post surgery when a visual analogue pain score was recorded before and after phenazocine administration. Any side effects were also recorded. Eighteen out of twenty patients had a reduction in their pain score. The incidence of side effects was low, with one patient experiencing mild nausea, one mild vomiting, one mild hypotension and one moderate sedation. Eleven of the patients commented on the unpleasant taste. We have found sublingual phenazocine to be useful in the treatment of postoperative pain.