Dose efficiency of erythropoiesis-stimulating agents for the treatment of patients with chemotherapy-induced anemia: a systematic review.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) increase red blood cell production in patients with chemotherapy-induced anemia (CIA). In Europe, short-acting ESAs (epoetin alfa, epoetin beta, epoetin zeta, and epoetin theta) and a long-acting ESA (darbepoetin alfa) are available to treat CIA. OBJECTIVE: This systematic review aimed to determine potential dose efficiency associated with the use of different ESAs for the treatment of CIA according to European labeling. METHODS: A systematic review of ESA studies with starting doses according to European labeling was conducted according to published methodology. Measures of dose efficiency were defined as mean weekly doses to achieve target hemoglobin level or final dose and dose adjustments (dose increase, decrease, or withheld). Electronic databases and grey literature sources were searched up to July 2012. Data were selected for analysis using an evidence hierarchy and quantitatively analyzed to assess statistical homogeneity. Where pooling of data was not appropriate, a narrative summary with descriptive statistics (medians and ranges) was reported. RESULTS: Fifty-five studies met the inclusion criteria. Twenty-five studies considered to represent the highest level of evidence were extracted and included in the analysis. The analysis showed a high degree of statistical heterogeneity, often precluding meta-analysis. The patients included in the analysis were representative of those encountered in clinical practice, and patient characteristics were similar between the short-acting and the darbepoetin alfa groups. Mean weekly doses appeared ~30% lower with darbepoetin alfa versus short-acting ESAs (median, 136.5 µg or 27,300 IU [range, 21,560-38,260 IU] vs 38,230 IU [range, 31,634-42,714 IU], respectively), resulting in a mean weekly dose ratio of 1:280. Darbepoetin alfa patients appeared to need fewer dose increases compared with short-acting ESAs (pooled, 0.75%; I(2) = 21% vs median 26.6% [range, 7.6%-44.6%]) and more dose decreases (median, 74% [range, 57%-75%] vs 22% [range, 2.8%-59%]). A similar percentage of darbepoetin alfa and short-acting ESA patients required a dose to be withheld (20% and 33% [2 studies] vs median 33.2% [range, 12.6%-51.1%]). CONCLUSIONS: Statistical heterogeneity between studies was high, although clinically the studies represented medical practice. Without randomized clinical trials directly comparing darbepoetin alfa and short-acting ESAs, these findings are tentative and future research is warranted. This review shows that good-quality, reliable data from head-to-head trials are lacking. The best available evidence comes from prospective ESA-arm data. Mean weekly doses, dose increases, and dose decreases suggest a dose efficiency for darbepoetin alfa compared with short-acting ESAs.

What is a rapid review? A methodological exploration of rapid reviews in Health Technology Assessments.

AIM: Commissioners of Health Technology Assessments require timely reviews to attain efficacious decisions on healthcare and treatments. In recent years, there has been an emergence of 'rapid reviews' within Health Technology Assessments; however, there is no known published guidance or agreed methodology within recognised systematic review or Health Technology Assessment guidelines. In order to answer the research question 'What is a rapid review and is methodology consistent in rapid reviews of Health Technology Assessments?', a study was undertaken in a sample of rapid review Health Technology Assessments from the Health Technology Assessment database within the Cochrane Library and other specialised Health Technology Assessment databases to investigate similarities and/or differences in rapid review methodology utilised. METHOD: In a targeted search to obtain a manageable sample of rapid reviews, the Health Technology Assessment database of The Cochrane Library and six international Health Technology Assessment databases were searched to locate rapid review Health Technology Assessments from 2000 onwards. Each rapid review was examined to investigate the individual methodology used for searching, inclusion screening, quality assessment, data extraction and synthesis. Methods of each rapid review were compared to investigate differences and/or similarities in methodologies used, in comparison with recognised methods for systematic reviews. RESULTS: Forty-six full rapid reviews and three extractable summaries of rapid reviews were included. There was a wide diversity of methodology, with some reviews utilising well-established systematic review methods, but many others diversifying in one or more areas, that is searching, inclusion screening, quality assessment, data extraction, synthesis methods, report structure and number of reviewers. There was a significant positive correlation between the number of recommended review methodologies utilised and length of time taken in months. CONCLUSIONS: Despite the number of rapid reviews published within Health Technology Assessments over recent years, there is no agreed and tested methodology and it is unclear how rapid reviews differ from systematic reviews. In a sample of Health Technology Assessment rapid reviews from 2000 to 2011, there was a wide diversity of methodology utilised in all aspects of rapid reviews. There is scope for wider research in this area to investigate the diversity of methods in more depth during each stage of the rapid review process, so that eventually recommendations could be made for clear and systematic methods for rapid reviews, thus facilitating equity and credibility of this type of important review methodology.

Epidemiology of chronic pain in denmark and sweden.

Introduction. Estimates on the epidemiology of chronic pain vary widely throughout Europe. It is unclear whether this variation reflects true differences between populations or methodological factors. Information on the epidemiology of chronic pain can support decision makers in allocating adequate health care resources. Methods. In order to obtain epidemiological data on chronic pain in Denmark and Sweden, we conducted a literature review of epidemiological data primarily on chronic noncancer pain, prioritising studies of highest quality, recency, and validity by conducting a systematic search for relevant studies. Following quality assessment, data were summarised and assigned to the research questions. Results. The prevalence of moderate to severe noncancer pain was estimated at 16% in Denmark and 18% in Sweden. Chronic pain impacts negatively on perceived health status, quality of life and is associated with increased cost. Despite using pain medications, a large proportion of chronic pain sufferers have inadequate pain control. There was a lack of high-quality and low-bias studies with clear inclusion criteria. Conclusions. In both Denmark and Sweden, chronic pain is a common health problem which is potentially undertreated and warrants attention of health care workers, policy makers and researchers. Future research should utilise clear reporting guidelines to assist decision and policy makers, in this important area.

Systematic review of tapentadol in chronic severe pain.

AIM: A systematic review of chronic pain treatment with strong opioids (step 3 WHO pain ladder) and a comparison to a new drug recently approved for the treatment of severe chronic pain in Europe, tapentadol (Palexia, Nucynta*), were performed. METHODS: Thirteen electronic databases were searched as well as a number of other sources from 1980 up to November 2010 for relevant randomized controlled clinical trials in chronic moderate and severe pain investigating at least one step 3 opioid. Chronic pain could be nociceptive or neuropathic, malignant or non-malignant, all systemic administrations were considered as well as trials of different lengths. Two separate analyses were performed, one only for trials which reported (at least as sub-groups) the outcome in patients with severe pain, the other including both moderate and severe pain conditions. With the exception of the direct comparison between tapentadol, oxycodone and placebo, indirect comparisons were performed based on a network analysis. Trials with an enriched or an enriched withdrawal design were excluded. Primary (pain intensity) and a number of secondary endpoints were evaluated, including pain relief (30% and 50%), patient global impression of change, quality of life, quality of sleep, discontinuations, as well as serious adverse events and selected adverse events. RESULTS: Only 10 trials were eligible for analysis of patients with severe pain (eight investigating tapentadol and two trials comparing buprenorphine patch vs placebo). For moderate and severe pain, 42 relevant trials were identified and indirect comparisons with transdermal buprenorphine, transdermal fentanyl, hydromorphone, morphine, and oxymorphone were performed. This report focuses on the network analysis. Tapentadol showed statistically favourable results over oxycodone for pain intensity, 30% and 50% pain relief, patient global impression of change (PGIC), and quality of life. Furthermore, some of the most important adverse events of chronic opioid treatment were significantly less frequent with tapentadol as compared to oxycodone, i.e. constipation, nausea, and vomiting; discontinuations due to these adverse events were found significantly reduced with tapentadol. Similar results were obtained for the network analysis, i.e. tapentadol was superior for the primary outcome (pain intensity) to hydromorphone and morphine, whereas fentanyl and oxymorphone showed trends in favour of these treatments. Significantly less frequent gastrointestinal adverse events of tapentadol were observed in comparison with fentanyl, hydromorphone, morphine, and oxymorphone, apparently leading to significantly reduced treatment discontinuations (for any reason). CONCLUSIONS: Taken together, the benefit-risk ratio of tapentadol appears to be improved compared to step 3 opioids.

Epidemiology of chronic non-cancer pain in Europe: narrative review of prevalence, pain treatments and pain impact.

BACKGROUND: Estimates on the epidemiology of chronic non-cancer pain vary widely throughout Europe. It is unclear whether this variation reflects true population differences or methodological factors. Such epidemiological information supports European decision makers in allocating healthcare resources. OBJECTIVE: Pan-Europe epidemiological data about chronic non-cancer pain was obtained using systematic review principles in searching and summarising results. METHODS: Multiple databases (MEDLINE, EMBASE, Cochrane Library, CRD Databases, and GIN) were systematically searched for primary studies containing epidemiological data on chronic non-cancer pain in Europe excluding studies that solely concerned migraines, headaches and pain associated with specific disease conditions. The studies were prioritised according to quality, recency and validity. MAIN OUTCOMES: Eighteen research questions concerning aspects of chronic pain included: prevalence; incidence; pain treatments, control and compliance; treatment satisfaction; and quality of life and economic impacts. RESULTS: The search yielded 16 619 references and 45 were relevant to Europe. Studies for each question were selected that provided the most recent, representative and valid data. There was a clear lack of studies concerning chronic non-cancer pain in Europe as a whole. The 1-month prevalence of moderate-to-severe non-cancer chronic pain was 19%. Chronic pain significantly impacted on patient-perceived health status, affected everyday activities including economic pursuits and personal relationships, and was significantly associated with depressive symptoms. The majority relied on drugs for pain control and NSAIDs were the most frequent drug choice. Despite pain medications, a large proportion had inadequate pain control. CONCLUSION: To the authors' knowledge this is the most comprehensive literature review on epidemiological data in this field. It is clear that chronic pain has a dramatic impact on European society. Since chronic non-cancer pain is treated differently from cancer-related pain, the lack of data in this area clearly underlines the need for decision makers in healthcare to gather further epidemiological data.