MishenMed: Statistical Consulting for Clinical Trials

 What is the difference between end of treatment and end of study ? There are two different CRF form page, one for EOT , the other for EOS.  End of treatment: it is not same as the concept for end of study. End of treatment occurs when subjects are treated and disease progression or lack of tolerability happens. If a subject who discontinue study treatment for any reason other than PD will be followed for response and survival. Otherwise, the subject will be followed for survival only. The reasons for end of treatment or end of study may be the same, such as PD,  AE, Death, lost to follow-up, withdraw by subjects, study terminated by sponsor.  What is TEAE ? How to define them ? First, TEAE refers to treatment emergent adverse event. 1. A treatment-emergent adverse event is defined as any event not present prior to the initiation of the drug treatment  2.  Any event already present that worsens in either intensity or frequency following exposure to the...

How to design a demographic table? What factors should be included? 1. Talk with the clinicians, let them make decisions based on some clinical meanings. For example, whether these baseline factors will impact the efficacy endpoints? 2. check the inclusion/exclusion criteria, make sure the enrolled patients meet the protocol criteria/meet the target population.  For example, age, disease stage, prior treatment.  For example, for breast cancer, subjects more than 65 years old then can be enrolled.  3. check with the CRF DM page, DM table from previous studies, Adam specifications 

 Briefly, Hy’s Law cases have the following three components: 1.The drug causes hepatocellular injury, generally shown by a higher incidence of 3-fold or greater elevations above the ULN of ALT or AST than the (nonhepatotoxic) control drug or placebo 2.Among trial subjects showing such AT elevations, often with ATs much greater than 3xULN, one or more also show elevation of serum TBL to >2xULN, without initial findings of cholestasis (elevated serum ALP) 3.No other reason can be found to explain the combination of increased AT and TBL, such as viral hepatitis A, B, or C; preexisting or acute liver disease; or another drug capable of causing the observed injury Finding one Hy’s Law case in the clinical trial database is worrisome; Finding two is considered highly predictive that the drug has the potential to cause severe DILI when given to a larger population. Clinical trials of the beta blocker dilevalol (enantiomer of labetalol, a diastereoisomeric mixture) showed two such case...

  A subscription-based product of the  International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use  (ICH), MedDRA or Medical Dictionary for Regulatory Activities is a clinically validated international  medical terminology  dictionary- thesaurus  used by regulatory authorities and the biopharmaceutical industry during the regulatory process, from pre-marketing (clinical research phase 0 to phase 3) to post-marketing activities (pharmacovigilance or clinical research phase 4), and for safety information data entry, retrieval, evaluation, and presentation.  it is the  adverse event  classification dictionary The MedDRA dictionary is organized with a five-level hierarchy. The highest or broadest level is System Organ Class (SOC), further divided into High-Level Group Terms (HLGT), High-Level Terms (HLT), Preferred Terms (PT), and finally into the most granular Lowest Level Terms (LLT). [6]  In additio...

What is ATC ? The Anatomical Therapeutic Chemical ( ATC ) Classification System is a drug classification system that classifies the active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemical properties. The classification system is maintained by the World Health Organization (WHO). This  pharmaceutical coding system  divides drugs into different groups according to the organ or system on which they act, their  therapeutic  intent or nature, and the drug's  chemical characteristics .  Different brands share the same code if they have the same active substance and indications. Each bottom-level ATC code stands for a pharmaceutically used substance, or a combination of substances, in a single indication (or use).  This means that one drug can have more than one code, for example  acetylsalicylic acid  (aspirin) has  A01AD05  as a drug for local  oral  tre...