Description of Event or Problem · 1
THE NODIFY XL2 TEST, MADE BY BIODESIX, IS FLAWED. IT IS FDA APPROVED AND CMS APPROVED. THE TEST IS FOR PATIENTS WHO HAVE A LUNG NODULE WITH A PRE-TEST PROBABILITY OF CANCER FROM 10-50%. IT IS A BLOOD TEST. THE TEST REPORTS TO THE DOCTOR AND PATIENT THE PROBABILITY THAT THE LUNG NODULE IS CANCER. IT USES BAYES' THEOREM TO DO THIS. IT CAME TO MDACC FOR A CLINICAL TRIAL. AS A PHYSICIAN AT MDACC, I REVIEWED THE TEST AND METHODS. THE TEST HAS THREE POSSIBLE CATEGORIES OF RESULTS ¿ LIKELY BENIGN, REDUCED RISK, AND INDETERMINATE. IF THE RESULT IS LIKELY BENIGN OR REDUCED RISK, IT PROVIDES THE PROBABILITY OF THE NODULE BEING MALIGNANT AS THE TEST RESULT. THE METHOD OF CALCULATION IS WRONG AS APPLIED TO THE REDUCED RISK GROUP. THIS IS BECAUSE THEY USED AN INAPPROPRIATE FORMULA TO CALCULATE THE LIKELIHOOD RATIO (LR) WHICH IS USED IN BAYES' THEOREM. THE CONSEQUENCE IS THAT THE LR THEY USE IS MUCH LOWER THAN IT SHOULD BE, SO PATIENTS WITH A "REDUCED RISK" RESULT ARE BEING PROVIDED WITH AN ESTIMATE OF THE ODDS OF CANCER THAT IS ROUGHLY THREE TIMES LOWER THAN THE TRUE ODDS. I REVIEWED HOW NODIFY XL2 CALCULATES THE PROBABILITY OF CANCER AND VERIFIED WITH THE COMPANY THAT MY UNDERSTANDING WAS CORRECT. I REVIEWED THIS WITH 4 DIFFERENT PHD BIOSTATISTICIANS AT MD ANDERSON CANCER CENTER. ALL FOUR SAID THE METHODOLOGY FOR CALCULATING THE LIKELIHOOD RATIO FOR THE REDUCED RISK GROUP WAS INDEED INCORRECT. THIS IS IMPORTANT, SINCE PATIENTS WITH A HIGHER RISK OF CANCER WOULD NORMALLY GET A BIOPSY, WHILE PATIENTS WITH A PERCEIVED LOWER RISK OF CANCER WILL USUALLY BE WATCHED. THE FALSELY LOW ESTIMATE OF CANCER RISK MAY RESULT IN A DELAY IN CANCER DIAGNOSIS. A DELAY IN DIAGNOSIS AND TREATMENT MAY PROVIDE THE CANCER THE OPPORTUNITY TO METASTASIZE (I.E. SPREAD) SO THAT WHAT WAS ONCE A CURABLE DISEASE BECOMES INCURABLE. FDA SAFETY REPORT ID # (B)(4).