The Norwegian General Practice – Nursing Home criteria (NORGEP-NH) for potentially inappropriate medication use: A web-based Delphi study

Objective. To develop a set of explicit criteria for pharmacologically inappropriate medication use in nursing homes. Design. In an expert panel, a three-round Delphi consensus process was conducted via survey software. Setting. Norway. Subjects. Altogether 80 participants – specialists in geriatrics or clinical pharmacology, physicians in nursing homes and experienced pharmacists – agreed to participate in the survey. Of these, 62 completed the first round, and 49 panellists completed all three rounds (75.4% of those ultimately entering the survey). Main outcome measures. The authors developed a list of 27 criteria based on the Norwegian General Practice (NORGEP) criteria, literature, and clinical experience. The main outcome measure was the panellists’ evaluation of the clinical relevance of each suggested criterion on a digital Likert scale from 1 (no clinical relevance) to 10. In the first round panellists could also suggest new criteria to be included in the process. For each criterion, degree of consensus was based on the average Likert score and corresponding standard deviation (SD). Results. A list of 34 explicit criteria for potentially inappropriate medication use in nursing homes was developed through a three-round web-based Delphi consensus process. Degree of consensus increased with each round. No criterion was voted out. Suggestions from the panel led to the inclusion of seven additional criteria in round two. Implications. The NORGEP-NH list may serve as a tool in the prescribing process and in medication list reviews and may also be used in quality assessment and for research purposes

Clinical drug trials in general practice: a 10-year overview of protocols

Background Drugs predominantly prescribed in general practice should ideally be tested in that setting; however, little is known about drug trials in general practice. Our aim was to describe drug trials in Norwegian general practice over the period of a decade. Methods The present work concerns a 10-year retrospective study of protocols submitted to the Norwegian national medicines agency (1998 to 2007) identifying all studies involving general practitioners (GPs) as clinical investigator(s). We analyzed the number of trials, drug company involvement, patients, participating doctors, payment, medications tested and main diagnostic criteria for inclusion. We also analyzed one trial in greater detail. Results Out of 2,054 clinical drug trials, 196 (9.5%) were undertaken in general practice; 93% were multinational, 96% were industry funded and 77% included patients both from general practice and specialist care. The trials were planned to be completed in the period 1998 to 2012. A total of 23,000 patients in Norway and 340,000 patients internationally were planned to be included in the 196 trials. A median of 5 GPs participated in each trial (range 1 to 402). Only 0.7% of 831 GP investigators had general practice university affiliations. Median payment for participating investigators was €1,900 (range €0 to 13,500) per patient completing the trial. A total of 30 pharmaceutical companies were involved. The drugs most commonly studied were antidiabetics (21%), obstructive airway disease medications (12%), agents acting on the renin-angiotensin system (10%), and lipid modifying agents (10%). One trial, presented in more detail, had several characteristics of a seeding or marketing trial. Conclusions Only one in four drug trials involving general practice were solely general practice trials and almost all were industry initiated without input from academic general practice. There was a large variation in the number of patients, participating doctors, and economic compensation for trial investigators, with some investigators receiving substantial payments

Clinical drug trials in general practice: how well are external validity issues reported?

Background When reading a report of a clinical trial, it should be possible to judge whether the results are relevant for your patients. Issues affecting the external validity or generalizability of a trial should therefore be reported. Our aim was to determine whether articles with published results from a complete cohort of drug trials conducted entirely or partly in general practice reported sufficient information about the trials to consider the external validity. Methods A cohort of 196 drug trials in Norwegian general practice was previously identified from the Norwegian Medicines Agency archive with year of application for approval 1998–2007. After comprehensive literature searches, 134 journal articles reporting results published from 2000 to 2015 were identified. In these articles, we considered the reporting of the following issues relevant for external validity: reporting of the clinical setting; selection of patients before inclusion in a trial; reporting of patients’ co-morbidity, co-medication or ethnicity; choice of primary outcome; and reporting of adverse events. Results Of these 134 articles, only 30 (22%) reported the clinical setting of the trial. The number of patients screened before enrolment was reported in 61 articles (46%). The primary outcome of the trial was a surrogate outcome for 60 trials (45%), a clinical outcome for 39 (29%) and a patient-reported outcome for 25 (19%). Clinical details of adverse events were reported in 124 (93%) articles. Co-morbidity of included participants was reported in 54 trials (40%), co-medication in 27 (20%) and race/ethnicity in 78 (58%). Conclusions The clinical setting of the trials, the selection of patients before enrolment, and co-morbidity or co-medication of participants was most commonly not reported, limiting the possibility to consider the generalizability of a trial. It may therefore be difficult for readers to judge whether drug trial results are applicable to clinical decision-making in general practice or when developing clinical guidelines

Rapid responses Topic collections Primary care Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials

Abstract Objective To estimate the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 inhibitors (coxibs), in patients with osteoarthritis of the knee. Design Systematic review and meta-analysis of randomised placebo controlled trials. Studies reviewed 23 trials including 10 845 patients, median age of 62.5 years. 7807 patients received adequate doses of NSAIDs and 3038 received placebo. The mean weighted baseline pain score was 64.2 mm on 100 mm visual analogue scale (VAS), and average duration of symptoms was 8.2 years. Main outcome measure Change in overall intensity of pain. Results Methodological quality of trials was acceptable, but 13 trials excluded patients before randomisation if they did not respond to NSAIDs. One trial provided long term data for pain that showed no significant effect of NSAIDs compared with placebo at one to four years. The pooled difference for pain on visual analogue scale in all included trials was 10.1 mm (95% confidence interval 7.4 to 12.8) or 15.6% better than placebo after 2-13 weeks. The results were heterogeneous, and the effect size for pain reduction was 0.32 (0.24 to 0.39) in a random effects model. In 10 trials that did not exclude non-responders to NSAID treatment the results were homogeneous, with an effect size for pain reduction of 0.23 (0.15 to 0.31). Conclusion NSAIDs can reduce short term pain in osteoarthritis of the knee slightly better than placebo, but the current analysis does not support long term use of NSAIDs for this condition. As serious adverse effects are associated with oral NSAIDs, only limited use can be recommended

Symphysis-fundus height measurement to predict small-for-gestational-age status at birth: A systematic review

Background: Fetal growth restriction is among the most common and complex problems in modern obstetrics. Symphysis-fundus (SF) height measurement is a non-invasive test that may help determine which women are at risk. This study is a systematic review of the literature on the accuracy of SF height measurement for the prediction of small-for-gestational-age (SGA) status at birth in unselected and low-risk pregnancies. Methods: The Medline, Embase, Cinahl, SweMed, and Cochrane Library databases were searched with no limitation on publication date (through September 2014), which returned 722 citations. Two reviewers then developed a short list of 51 publications of possible relevance and assessed them using the following inclusion criteria: cohort study of test accuracy performed in a routine prenatal care setting; SF height measurement for all participants; classification of SGA, defined as birth weight (BW) < 10th, 5th, or 3rd percentile or ≥ one or two standard deviations below the mean; study conducted in Northern, Western, or Central Europe; USA; Canada; Australia; or New Zealand; and sufficient data for 2 × 2 table construction. Quality of the included studies was assessed in duplicate using criteria suggested by the Cochrane Collaboration. Review Manager 5.3 software was used to analyze the data, including plotting of summary receiver operating curve spaces. Results: Eight studies were included in the final dataset and seven were included in summary analyses. The sensitivity of SF height measurement for SGA (BW < 10th percentile) prediction ranged from 0.27 to 0.76 and specificity ranged from 0.79 to 0.92. Positive and negative likelihood ratios ranged from 1.91 to 9.09 and from 0.29 to 0.83, respectively. Conclusions: SF height can serve as a clinical indicator along with other clinical findings, information about medical conditions, and previous obstetric history. However, SF height has high false-negative rates for SGA. Clinicians must understand the limitations of this test

Publication and non-publication of drug trial results: a 10-year cohort of trials in Norwegian general practice

Objectives Previously, we identified a 10-year cohort of protocols from applications to the Norwegian Medicines Agency 1998–2007, consisting of 196 drug trials in general practice. The aim of this study was to examine whether trial results were published and whether trial funding and conflicts of interest were reported. Design Cohort study of trials with systematic searches for published results. Setting Clinical drug trials in Norwegian general practice. Methods We performed systematic literature searches of MEDLINE, Embase and CENTRAL to identify publications originating from each trial using characteristics such as test drug, comparator and patient groups as search terms. When no publication was identified, we contacted trial sponsors for information regarding trial completion and reference to any publications. Main outcome measures We determined the frequency of publication of trial results and trial characteristics associated with publication of results. Results Of the 196 trials, 5 were never started. Of the remaining 191 trials, 71% had results published in a journal, 11% had results publicly available elsewhere and 18% of trials had no results available. Publication was more common among trials with an active comparator drug (χ2 test, p=0.040), with a larger number of patients (total sample size≥median, p=0.010) and with a longer trial period (duration≥median, p=0.025). Trial funding was reported in 85% of publications and increased over time, as did reporting of conflicts of interest among authors. Among the 134 main journal articles from the trials, 60% presented statistically significant results for the investigational drug, and the conclusion of the article was favourable towards the test drug in 78% of papers. Conclusions We did not identify any journal publication of results for 29% of the general practice drug trials. Trials with an active comparator, larger and longer trials were more likely to be published

Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials

Objective To estimate the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 inhibitors (coxibs), in patients with osteoarthritis of the knee. Design Systematic review and meta-analysis of randomised placebo controlled trials. Studies reviewed 23 trials including 10 845 patients, median age of 62.5 years. 7807 patients received adequate doses of NSAIDs and 3038 received placebo. The mean weighted baseline pain score was 64.2 mm on 100 mm visual analogue scale (VAS), and average duration of symptoms was 8.2 years. Main outcome measure Change in overall intensity of pain. Results Methodological quality of trials was acceptable, but 13 trials excluded patients before randomisation if they did not respond to NSAIDs. One trial provided long term data for pain that showed no significant effect of NSAIDs compared with placebo at one to four years. The pooled difference for pain on visual analogue scale in all included trials was 10.1 mm (95% confidence interval 7.4 to 12.8) or 15.6% better than placebo after 2-13 weeks. The results were heterogeneous, and the effect size for pain reduction was 0.32 (0.24 to 0.39) in a random effects model. In 10 trials that did not exclude non-responders to NSAID treatment the results were homogeneous, with an effect size for pain reduction of 0.23 (0.15 to 0.31). Conclusion NSAIDs can reduce short term pain in osteoarthritis of the knee slightly better than placebo, but the current analysis does not support long term use of NSAIDs for this condition. As serious adverse effects are associated with oral NSAIDs, only limited use can be recommended