[RESEARCH] Effect of European Clinical Trials Directive on academic drug trials in Denmark: retrospective study of applications to the Danish Medicines Agency 1993-2006
Objective To determine the impact of the European Union’s Clinical Trials Directive on the number of academic drug trials carried out in Denmark.
Design Retrospective review of applications for drug trials to the Danish Medicines Agency, 1993-2006.
Review methods Applications for drug trials for alternate years were classified as academic or commercial trials. A random subset of academic trials was reviewed for number of participants in and intended monitoring of the trials.
Results Academic and commercial drug trials showed an identical steady decline from 1993 to 2006 and no noticeable change after 2004 when good clinical practice became mandatory for academic trials.
Conclusion The Clinical Trials Directive introduced in May 2004 to ensure good clinical practice for academic drug trials was not associated with a decline in research activity in Denmark; presumably because good clinical practice units had already been in place in Danish universities since 1999. With such an infrastructure academic researchers can do drug trials under the same regulations as drug companies.
Zinc Does Not Prevent Diabetes
Filed under: Type 2, Adult Onset, Research, Products
Despite claims by zinc supplement manufacturers that the pills can help prevent type 2 diabetes, clinical trials do not support this hypothesis.
Laboratory research suggests that zinc helps promote the production and action of insulin. A four-week study of 56 obese women found that zinc did not have an effect on factors associated with the development of diabetes. This study was an example of one trial that treated 56 people with either zinc or a placebo for four weeks and found no effect. This single trial is too small and too short to tell us anything about the effectiveness of zinc in preventing the development of type 2 diabetes.
Research does support that zinc plays a key role in the regulation of insulin production and glucose utilization. Diabetics have shown a zinc deficiency, which impairs their ability to use glucose. However this fact does not confirm zinc as a supplement to prevent the development of diabetes. I apologize it's a nonevent insofar as news. But look at it this way - it's one trial. Nobody says you have to cross it off your list because 56 obese women didn't see a change in their risk factors for developing diabetes. One study is not gospel.
History underway in type 1 diabetes cure
Filed under: Type 1, Childhood, Research, Events, Support
Dr. Faustman's lab is currently collecting blood samples from individuals with established Type 1 diabetes. These samples are being used to quantify the number of autoreactive T-cells and develop the adequate dosage for Phase 1 of human trials to cure Type 1 diabetes.
The research has been presented and the NIH confirmed it. By reeducating the confused T-cells and instructing them not to attack healthy islets, an apparent cure of established type 1 diabetes in non-obese diabetic mice is possible. Now, Dr. Faustman is collecting human samples to bestow the same cure for diabetes in humans.
If you wish to be a part of this revolutionary event for curing Type 1 diabetes, please contact the Clinical Coordinator or call Dr. Faustman's lab at (617) 726-4084. Each participant is asked to bring a control person along with them - an unrelated person without Type 1 diabetes or another autoimmune disease. Diabetic or not - you can be a part of history in curing Type 1 diabetes!
[RESEARCH] Doctors' versus patients' global assessments of treatment effectiveness: empirical survey of diverse treatments in clinical trials
Objective To examine whether doctors’ global assessments of treatment effects agree with patients’ global assessments.
Design Survey of trials included in systematic reviews of treatments for diverse conditions.
Data sources Cochrane database of systematic reviews.
Data extracted Data on patients’ global assessments and on doctors’ global assessment for the same treatment against the same comparator.
Main outcome measures Relative odds ratio (ratio of odds ratios of global improvement with the experimental intervention versus control according to doctors compared with patients), and improvement rates according to doctors and patients.
Results Doctors’ global assessments were compared with patients’ global assessments for 63 different treatment comparisons (240 trials) in 18 conditions. The summary relative odds ratio across the comparisons was not significant (0.98, 95% confidence interval 0.88 to 1.08; I2=0%, 95% confidence interval 0% to 30%). In 62 of the 63 comparisons the effects of treatment rated by patients and by doctors did not differ beyond chance, but for single comparisons the confidence intervals were large. Rates of improvement on average did not differ between doctors’ assessments and patients’ assessments (summary relative odds ratio 0.98, 0.88 to 1.06; I2=0%, 0% to 24%).
Conclusion Doctors’ global assessments of the effects of treatments are on average similar to those of patients.
[RESEARCH] Limitations of rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study
Objective To evaluate the limitations of rapid tests for HIV-1.
Design Diagnostic test accuracy study.
Setting Rural Rakai, Uganda.
Participants 1517 males aged 15-49 screened for trials of circumcision for HIV prevention.
Main outcome measures Sensitivity, specificity, negative predictive values, and positive predictive values of an algorithm using three rapid tests for HIV, compared with the results of enzyme immunoassay and western blotting as the optimal methods.
Results Rapid test results were evaluated by enzyme immunoassay and western blotting. Sensitivity was 97.7%. Among 639 samples where the strength of positive bands was coded if the sample showed positivity for HIV, the algorithm had low specificity (94.1%) and a low positive predictive value (74.0%). Exclusion of 37 samples (5.8%) with a weak positive band improved the specificity (99.6%) and positive predictive value (97.7%).
Conclusion Weak positive bands on rapid tests for HIV should be confirmed by enzyme immunoassay and western blotting before disclosing the diagnosis. Programmes using rapid tests routinely should use standard serological assays for quality control.
Trial registration Clinical Trials NCT00425984.
[RESEARCH] Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence
Objective To examine the effectiveness of parenteral corticosteroids for the relief of acute severe migraine headache and prevention of recurrent headaches.
Design Meta-analysis.
Data sources Electronic databases (Cochrane Central Register of Controlled Trials, Medline, Embase, LILACS, and CINAHL), conference proceedings, clinical practice guidelines, contacts with industry, and correspondence with authors.
Selection criteria Randomised controlled trials in which corticosteroids (alone or combined with standard abortive therapy) were compared with placebo or any other standard treatment for acute migraine in adults.
Review methods Two reviewers independently assessed relevance, inclusion, and study quality. Weighted mean differences and relative risks were calculated and are reported with 95% confidence intervals.
Results From 666 potentially relevant abstracts, seven studies met the inclusion criteria. All included trials used standard abortive therapy and subsequently compared single dose parenteral dexamethasone with placebo, examining pain relief and recurrence of headache within 72 hours. Dexamethasone and placebo provided similar acute pain reduction (weighted mean difference 0.37, 95% confidence interval –0.20 to 0.94). Dexamethasone was, however, more effective than placebo in reducing recurrence rates (relative risk 0.74, 95% confidence interval 0.60 to 0.90). Side effect profiles between dexamethasone and placebo groups were similar.
Conclusion When added to standard abortive therapy for migraine headache, single dose parenteral dexamethasone is associated with a 26% relative reduction in headache recurrence (number needed to treat=9) within 72 hours.
[RESEARCH] Internal and external validity of cluster randomised trials: systematic review of recent trials
Objectives To assess aspects of the internal validity of recently published cluster randomised trials and explore the reporting of information useful in assessing the external validity of these trials.
Design Review of 34 cluster randomised trials in primary care published in 2004 and 2005 in seven journals (British Medical Journal, British Journal of General Practice, Family Practice, Preventive Medicine, Annals of Internal Medicine, Journal of General Internal Medicine, Pediatrics).
Data sources National Library of Medicine (Medline) via PubMed.
Data extraction To assess aspects of internal validity we extracted data on appropriateness of sample size calculations and analyses, methods of identifying and recruiting individual participants, and blinding. To explore reporting of information useful in assessing external validity we extracted data on cluster eligibility, cluster inclusion and retention, cluster generalisability, and the feasibility and acceptability of the intervention to health providers in clusters.
Results 21 (62%) trials accounted for clustering in sample size calculations and 30 (88%) in the analysis; about a quarter were potentially biased because of procedures surrounding recruitment and identification of patients; individual participants were blind to allocation status in 19 (56%) and outcome assessors were blind in 15 (44%). In almost half the reports, information relating to generalisability of clusters was poorly reported, and in two fifths there was no information about the feasibility and acceptability of the intervention.
Conclusions Cluster randomised trials are essential for evaluating certain types of interventions. Issues affecting their internal validity, such as appropriate sample size calculations and analysis, have been widely disseminated and are now better addressed by researchers. Blinding of those identifying and recruiting patients to allocation status is recommended but is not always carried out. There may be fewer barriers to internal validity in trials in which individual participants are not recruited. External validity seems poorly addressed in many trials, yet is arguably as important as internal validity in judging quality as a basis for healthcare intervention.
[RESEARCH] Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials
Objective To explore the extent to which components of composite end points in randomised controlled trials vary in importance to patients, the frequency of events in the more and less important components, and the extent of variability in the relative risk reductions across components.
Design Systematic review of randomised controlled trials.
Data sources Cardiovascular randomised controlled trials published in the Lancet, Annals of Internal Medicine, Circulation, European Heart Journal, JAMA, and New England Journal of Medicine, from 1 January 2002 to 30 June 2003. Component end points of composite end points were categorised according to importance to patients as fatal, critical, major, moderate, or minor.
Results Of 114 identified randomised controlled trials that included a composite end point of importance to patients, 68% (n=77) reported complete component data for the primary composite end point; almost all (98%; n=112) primary composite end points included a fatal end point. Of 84 composite end points for which component data were available, 54% (n=45) showed large or moderate gradients in both importance to patients and magnitude of effect across components. When analysed by categories of importance to patients, the most important components were associated with lower event rates in the control group (medians of 3.3-3.7% for fatal, critical, and major outcomes; 12.3% for moderate outcomes; and 8.0% for minor outcomes). Components of greater importance to patients were associated with smaller treatment effects than less important ones (relative risk reduction of 8% for death and 33% for components of minor importance to patients).
Conclusion The use of composite end points in cardiovascular trials is frequently complicated by large gradients in importance to patients and in magnitude of the effect of treatment across component end points. Higher event rates and larger treatment effects associated with less important components may result in misleading impressions of the impact of treatment.
Pig Islets 10 Years and Counting
Filed under: Type 1, Childhood, Lifestyle, Research, Events, Support
In 1996 a 41 year old male (a type 1 diabetic for 18 years) was injected with biocapsules containing pig islets to regulate his blood sugar level. The transplanted cells helped reduce the patient's insulin requirement by 34% for over a year, which provided better control. By 2005 the patient's glycated hemoglobin levels (HbA1c) remained lower than the pre-transplant levels.
Ten years later, the patent contacted Living Cell Technologies to inform them that he believed the transplanted pig islets were still alive and well. After tests were conducted, it was concluded that the pig cells were (as he reported) still functioning. This proved that the LCT patented technology for xenotransplantation was effective. It allows the islets to survive at least ten years in a micro-capsule coating and continue to release insulin into the patient's bloodstream without immune suppression. After tests we conducted on the type of insulin present in the patients blood - it was with 100% certainty that it was pig and not human insulin.
LCT has significantly advanced the encapsulation process since the 1996 clinical trial and there is an even greater understanding and control over the longevity and robustness of the encapsulation process, as well as the porcine islet cells. LCT will be trialing the DiabeCell pig islet cell transplant in patients in a phase I/IIa clinical trial, expected to begin in Quarter 2, 2007. In addition, LCT is awaiting approval to conduct an additional trial in New Zealand this year with a different treatment protocol. Subsequent trials in the US or Europe are intended following initial results from these studies.
If overseas trials are coming through with flying colors - why aren't we doing this yet? C'mon USA - where's your competitive spirit? All these pigs up in Spring Point might be put to good use, after all. Oink Oink.
[RESEARCH] Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis
Objective To evaluate the effect of oral decontamination on the incidence of ventilator associated pneumonia and mortality in mechanically ventilated adults.
Design Systematic review and meta-analysis.
Data sources Medline, Embase, CINAHL, the Cochrane Library, trials registers, reference lists, conference proceedings, and investigators in the specialty.
Review methods Two independent reviewers screened studies for inclusion, assessed trial quality, and extracted data. Eligible trials were randomised controlled trials enrolling mechanically ventilated adults that compared the effects of daily oral application of antibiotics or antiseptics with no prophylaxis.
Results 11 trials totalling 3242 patients met the inclusion criteria. Among four trials with 1098 patients, oral application of antibiotics did not significantly reduce the incidence of ventilator associated pneumonia (relative risk 0.69, 95% confidence interval 0.41 to 1.18). In seven trials with 2144 patients, however, oral application of antiseptics significantly reduced the incidence of ventilator associated pneumonia (0.56, 0.39 to 0.81). When the results of the 11 trials were pooled, rates of ventilator associated pneumonia were lower among patients receiving either method of oral decontamination (0.61, 0.45 to 0.82). Mortality was not influenced by prophylaxis with either antibiotics (0.94, 0.73 to 1.21) or antiseptics (0.96, 0.69 to 1.33) nor was duration of mechanical ventilation or stay in the intensive care unit.
Conclusions Oral decontamination of mechanically ventilated adults using antiseptics is associated with a lower risk of ventilator associated pneumonia. Neither antiseptic nor antibiotic oral decontamination reduced mortality or duration of mechanical ventilation or stay in the intensive care unit.