How to Tell When A Drug Company Fibs About Clinical Trial Results

Cardiac MRI is a precise and commonly used method of measuring cardiac changes in clinical trials. MRI assessments were conducted for six months after heart attack patients were enrolled and treated with either Prochymal or a placebo, but Osiris purports to be reporting interim, one-year results. When were the MRIs conducted in the Prochymal trial? Osiris doesn't specify, which clouds the reported results, especially if MRIs were not conducted at 12 months follow up.

Osiris:

Patients receiving Prochymal had significantly less cardiac hypertrophy, as measured by cardiac MRI, compared to patients receiving placebo (p less than 0.05). Patients treated with Prochymal also experienced significantly less stress-induced ventricular arrhythmia (p less than 0.05). Cardiac hypertrophy and ventricular arrhythmia are indicators of pathological remodeling following heart injury and provide insight into the mechanism by which mesenchymal stem cells attenuate heart injury following a myocardial infarction.

This is the paragraph where Osiris claims positive results based on Prochymal beating placebo across two efficacy endpoints. Sounds impressive except none of the Prochymal benefits disclosed by Osiris are predefined endpoints in the phase II trial.

Osiris appears to have thrown out the real endpoints called for in the phase II trial and replaced them with new endpoints which just happen to show Prochymal in the best light. Why would Osiris do this? Perhaps the pre-defined endpoints in the study all failed? That's a pretty safe assumption when companies decide to swap out trial endpoints with no disclosure or explanation.

Again, here is where Clinicaltrials.gov is a good fact checker. The site's listing of the Prochymal acute myocardial infarction (AMI) study shows left ventricular end systolic volume (ESV) as the primary endpoint. Secondary endpoints in the study are left ventricular ejection fraction (LVEF), infarct size and major adverse cardiovascular events (MACE).

ESV measures the volume of blood in a ventricle at the end of the heart's contraction -- an important assessment of how well the heart is able to pump blood to the rest of the body. More blood left in the ventricle after contraction signals a weakened a heart muscle.

Similarly, LVEF measures the percentage of blood that is pumped out of the ventricle with each heartbeat. A higher LVEF signals a stronger heart.