Statins: "Funding from the test drug company was associated with results (OR=20) and conclusions (OR=35) that favor the test drug."

In this 20 minutes lecture by Beatrice Golomb, she mentions (among others) a interesting study:


So funding from the industry can skew research results? Who would have though that!?

Study weaknesses included:

• Inadequate blinding
• Lack of concealment of allocation
• Poor follow-up
• Lack of intention-to-treat analyses

It is always the same: Blinding, blinding, blinding and proper controls – at least they got the last one right. A study that was not properly blinded may be helpful to explore association ("Could it be?") or safety at a phase I stage, but to draw definite conclusions one needs properly blinded and controlled studies.

Here's the abstract:

Factors Associated with Findings of Published Trials of Drug–Drug Comparisons: Why Some Statins Appear More Efficacious than Others
Lisa Bero, Fieke Oostvogel, Peter Bacchetti, and Kirby Lee

Abstract


Background
Published pharmaceutical industry–sponsored trials are more likely than non-industry-sponsored trials to report results and conclusions that favor drug over placebo. Little is known about potential biases in drug–drug comparisons. This study examined associations between research funding source, study design characteristics aimed at reducing bias, and other factors that potentially influence results and conclusions in randomized controlled trials (RCTs) of statin–drug comparisons.

Methods and Findings
This is a cross-sectional study of 192 published RCTs comparing a statin drug to another statin drug or non-statin drug.

Data on concealment of allocation, selection bias, blinding, sample size, disclosed funding source, financial ties of authors, results for primary outcomes, and author conclusions were extracted by two coders (weighted kappa 0.80 to 0.97). Univariate and multivariate logistic regression identified associations between independent variables and favorable results and conclusions. Of the RCTs, 50% (95/192) were funded by industry, and 37% (70/192) did not disclose any funding source.

Looking at the totality of available evidence, we found that almost all studies (98%, 189/192) used only surrogate outcome measures. Moreover, study design weaknesses common to published statin–drug comparisons included inadequate blinding, lack of concealment of allocation, poor follow-up, and lack of intention-to-treat analyses.

In multivariate analysis of the full sample, trials with adequate blinding were less likely to report results favoring the test drug, and sample size was associated with favorable conclusions when controlling for other factors.

In multivariate analysis of industry-funded RCTs, funding from the test drug company was associated with results (odds ratio = 20.16 [95% confidence interval 4.37–92.98], p < 0.001) and conclusions (odds ratio = 34.55 [95% confidence interval 7.09–168.4], p < 0.001) that favor the test drug when controlling for other factors. Studies with adequate blinding were less likely to report statistically significant results favoring the test drug.


Conclusions
RCTs of head-to-head comparisons of statins with other drugs are more likely to report results and conclusions favoring the sponsor's product compared to the comparator drug. This bias in drug–drug comparison trials should be considered when making decisions regarding drug choice.

ME/CFS and Peripheral Pulse as a diagnostic tool

"Our research study explored how we might use the properties of the peripheral pulse as a diagnostic tool for CFS," said Julia Newton, an honorary consultant physician at the Newcastle upon Tyne Hospitals NHS Foundation Trust and within Newcastle University's Institute for Ageing and Health. "Pulse wave abnormalities were observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls."
…

"The normal homeostatic response to standing is to preserve the brain at all costs," explained Newton. "The body therefore aims to do what it can to get the blood back to the brain against gravity by increasing the heart rate and constricting the peripheral blood vessels. Our study focused on measuring and assessing pulses from multiple peripheral sites simultaneously in both CFS patients and controls in response to a posture change."
…

"With each heartbeat, the blood volume changes in the vascular bed of the tissue and the amount of light shone onto the skin by the probes varies in synchrony with this, giving a clear pulse with each heart beat," explained John Allen, a clinical scientist from the Regional Medical Physics Department of Newcastle's Freeman Hospital. "The pulse waveform has many features in terms of its size, shape and the time for it to get from the heart to the periphery as well as beat-by-beat variability. We used special computer analysis techniques to extract various pulse features and compared these to data from normal subjects to provide the diagnostic information."
…

"Further research applied to a larger number of subjects should help decide the most reliable combination of pulse features to measure so that the technique can be applied to a general population for screening of CFS with full confidence."

(via CO-CURE)

Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker

John Allen, Alan Murray, Costanzo Di Maria and Julia L Newton

Abstract

Autonomic nervous system dysfunction is frequently reported in chronic fatigue syndrome (CFS) with orthostatic intolerance, a common symptom that can be objectively assessed.

The frequent finding of autonomic dysfunction and symptoms on standing has the potential to provide a diagnostic biomarker in chronic fatigue.

In this study we explored the clinical value of non-invasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing.

Multi-site PPG pulses were collected from tissue pads of the ears, fingers and toes of 14 patients with CFS and 14 age-matched sedentary subjects using a measurement protocol of a 10 min baseline (subject supine) followed by 3 min of tilting on a tilt table (head-up to 70°).

Percentage change in pulse timing (pulse transit time, PTTf) and pulse amplitude (AMP) at each site were calculated using beat-to-beat pulse wave analysis.

A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group (using summed absolute percentage change in PTTf for ear, finger and toe sites, median change of 26% for CFS and 37% for control with p = 0.002).

There were no significant differences between subject groups for the AMP measure at any site.

Changes in AMP with tilt were, however, weakly significantly and negatively correlated with fatigue severity (p < 0.05).

Receiver operating characteristic (ROC) analysis of timing measures produced an area under the curve of 0.81.

Experimental linear discriminant classification analysis comparing both timing and amplitude measures produced an overall diagnostic accuracy of 82%.

Pulse wave abnormalities have been observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls.

14 patients and 14 controls? Could be a bit more. But they choose sedentary controls, which is good.

PDF available here.