Riviste scientifiche

Noncompletion and nonpublication of trials studying rare diseases: A cross-sectional analysis

PLoS Medicine - %age fa

by Chris A. Rees, Natalie Pica, Michael C. Monuteaux, Florence T. Bourgeois

Background

Rare diseases affect as many as 60 million people in the United States and Europe. However, most rare diseases lack effective therapies and are in critical need of clinical research. Our objective was to determine the frequency of noncompletion and nonpublication of trials studying rare diseases.

Methods and findings

We conducted a cross-sectional analysis of randomized clinical trials studying rare diseases as defined by the Genetic and Rare Disease Information Center database that were registered in ClinicalTrials.gov between January 1, 2010, and December 31, 2012, and completed or discontinued by December 31, 2014. Our main outcome measures were the frequency of trial noncompletion and, among completed studies, frequency of trial nonpublication at 2 and 4 years following trial completion. Reasons for discontinuation were extracted from the registry, and trial sponsors were contacted for additional information, as needed. Two independent investigators performed publication searches for each trial in PubMed, EMBASE, and GoogleScholar, allowing for a minimum of 45 months between trial completion and publication. When a publication could not be identified, trial sponsors were contacted to confirm publication status. The impact of funding source on trial noncompletion was assessed with multivariable logistic regression, and the effect on time to publication was examined with Cox proportional hazards regression. Control variables included intervention type, trial phase, masking, enrollment, and study population. We analyzed 659 rare disease trials accounting for 70,305 enrolled patients. Industry was the primary funder for 327 trials (49.6%) and academic institutions for 184 trials (27.9%). There were 79 trials (12.0%) focused on pediatric populations. A total of 199 trials (30.2%) were discontinued. Lack of patient accrual (n = 64, 32.1%) and informative termination (n = 41, 20.6%) were the most common reasons for trial noncompletion. Among completed trials, 306 (66.5%) remained unpublished at 2 years and 142 (31.5%) at 4 years. In multivariable analyses, industry-funded trials were less likely to be discontinued than trials funded by healthcare centers (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.34–4.39, P = 0.003). We found no significant association between funding source and time to publication. A total of 18,148 patients were enrolled in trials that were discontinued or unpublished 4 years after completion. A potential limitation of our study is that certain interventional trials for rare diseases may not have been registered in ClinicalTrials.gov, in particular Phase 0 and Phase I trials, which are not required to be registered.

Conclusions

In this study, over half of clinical trials initiated for rare diseases were either discontinued or not published 4 years after completion, resulting in large numbers of patients with rare diseases exposed to interventions that did not lead to informative findings. Concerted efforts are needed to ensure that participation of patients in rare disease trials advances scientific knowledge and treatments for rare diseases.

Humans across cultures may share the same universal musical grammar

New Scientist - %age fa
Music appears to be made from the same simple building blocks of pitches and chords around the world, upending the prevailing view that universals don’t exist

Suspended animation for emergency medicine: your questions answered

New Scientist - %age fa
Yesterday, New Scientist broke the news that suspended animation has been tried on humans for the first time. Helen Thomson answers all your questions on this new procedure

Huge Earth-like worlds could host reservoirs of water deep underground

New Scientist - %age fa
Minerals containing water can exist at much higher pressures than we knew, so they could be hiding oceans’ worth of water deep within giant planets

Genetic screening of IVF embryos is unlikely to lead to smarter babies

New Scientist - %age fa
Can DNA analysis help prospective parents choose IVF embryos on the basis of future intelligence? A study suggests this approach would have little, if any, effect

Ants trapped for years in old Soviet nuclear bunker became cannibals

New Scientist - %age fa
A colony of ants survived for years in an old nuclear bunker despite having no obvious food source – probably because the ants began eating one another

Part of a vital Antarctic glacier has unexpectedly stopped thinning

New Scientist - %age fa
A UK team was surprised to find that, in the past six years, a glacier in the Antarctic has virtually paused thinning at its end, but a neighbouring glacier hasn't

Convert your dog's age into human years using this new formula

New Scientist - %age fa
Conventional wisdom says that one human year is the equivalent of seven dog years, but a new analysis suggests we’ve been getting this all wrong

Some women feel fetal kicks years after they've given birth

New Scientist - %age fa
Around 40 per cent of women in a survey experienced phantom fetal kicks, which is the feeling of a kicking fetus years after giving birth

Wearable artificial kidney works well in first tests in people

New Scientist - %age fa
A portable artificial kidney set has been used successfully by 15 people, and could free them from regular haemodialysis sessions

Duration of type 2 diabetes and remission rates after bariatric surgery in Sweden 2007–2015: A registry-based cohort study

PLoS Medicine - Me, 20/11/2019 - 23:00

by Anders Jans, Ingmar Näslund, Johan Ottosson, Eva Szabo, Erik Näslund, Erik Stenberg

Background

Although bariatric surgery is an effective treatment for type 2 diabetes (T2D) in patients with morbid obesity, further studies are needed to evaluate factors influencing the chance of achieving diabetes remission. The objective of the present study was to investigate the association between T2D duration and the chance of achieving remission of T2D after bariatric surgery.

Methods and findings

We conducted a nationwide register-based cohort study including all adult patients with T2D and BMI ≥ 35 kg/m2 who received primary bariatric surgery in Sweden between 2007 and 2015 identified through the Scandinavian Obesity Surgery Registry. The main outcome was remission of T2D, defined as being free from diabetes medication or as complete remission (HbA1c < 42 mmol/mol without medication). In all, 8,546 patients with T2D were included. Mean age was 47.8 ± 10.1 years, mean BMI was 42.2 ± 5.8 kg/m2, 5,277 (61.7%) were women, and mean HbA1c was 58.9 ± 17.4 mmol/mol. The proportion of patients free from diabetes medication 2 years after surgery was 76.6% (n = 6,499), and 69.9% at 5 years (n = 3,765). The chance of being free from T2D medication was less in patients with longer preoperative duration of diabetes both at 2 years (odds ratio [OR] 0.80/year, 95% CI 0.79–0.81, p < 0.001) and 5 years after surgery (OR 0.76/year, 95% CI 0.75–0.78, p < 0.001). Complete remission of T2D was achieved in 58.2% (n = 2,090) at 2 years, and 46.6% at 5 years (n = 681). The chance of achieving complete remission correlated negatively with the duration of diabetes (adjusted OR 0.87/year, 95% CI 0.85–0.89, p < 0.001), insulin treatment (adjusted OR 0.25, 95% CI 0.20–0.31, p < 0.001), age (adjusted OR 0.94/year, 95% CI 0.93–0.95, p < 0.001), and HbA1c at baseline (adjusted OR 0.98/mmol/mol, 95% CI 0.97–0.98, p < 0.001), but was greater among males (adjusted OR 1.57, 95% CI 1.29–1.90, p < 0.001) and patients with higher BMI at baseline (adjusted OR 1.07/kg/m2, 95% CI 1.05–1.09, p < 0.001). The main limitations of the study lie in its retrospective nature and the low availability of HbA1c values at long-term follow-up.

Conclusions

In this study, we found that remission of T2D after bariatric surgery was inversely associated with duration of diabetes and was highest among patients with recent onset and those without insulin treatment.

Semen seems to help female fruit flies remember things better

New Scientist - Me, 20/11/2019 - 20:00
A molecule in male fruit fly semen boosts females’ long-term memory – the first example of mating playing a role in cognition

Palm oil from Colombia is more climate and wildlife friendly

New Scientist - Me, 20/11/2019 - 20:00
Most oil palms in Colombia are planted on land previously used for grazing cattle, rather than land cleared of rainforests, making it a greener choice

Human activities could make a third of tropical African plants extinct

New Scientist - Me, 20/11/2019 - 20:00
A third of plant species in tropical Africa are potentially threatened with becoming extinct, which would put a huge strain on local populations

Artificial skin could be used to make video games more realistic

New Scientist - Me, 20/11/2019 - 19:00
A synthetic skin could help add the sensation of touch to prosthetic hands or give video games a more realistic feel

CERN boss: Big physics may be in a funk, but we need it more than ever

New Scientist - Me, 20/11/2019 - 19:00
The particle physics discoveries have dried up but in politically uncertain times CERN's cooperative model is an example to the world, says its chief Fabiola Gianotti

Hyperpalatable foods are a modern bogeyman. But what even are they?

New Scientist - Me, 20/11/2019 - 19:00
The idea that super-addictive foods are being engineered by corporate giants is a pervasive one. But trying to find science on this isn’t straightforward, says James Wong

See Venus and Jupiter next to each other in the sky this week

New Scientist - Me, 20/11/2019 - 19:00
Two of the brightest planets, Venus and Jupiter, are in conjuction this week, meaning they appear to line up with Earth in the sky. Here's how to spot them

Approval of golden rice could finally end vitamin A deficiency deaths

New Scientist - Me, 20/11/2019 - 19:00
Genetically modified golden rice finally seems set for approval where it is needed to address vitamin A deficiency, but anti-scientific misinformation campaigns continue, says Michael Le Page

Pigeons with broken wings get patched up with dog and sheep bones

New Scientist - Me, 20/11/2019 - 17:00
Pigeons with broken wing bones could take to the skies again once their fracture was set using lightweight splints made from dog or sheep bones
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