Considering publications by TDR pioneers [ 11- 13] and studies leading to FDA approval, indications and contraindications for TDR were defined [ 8, 14, 15].
Unfortunately, the approval indications for these drugs oftentimes are not defined clearly for the castration-resistant setting and, hence, may lead to their overuse and increase the incidence of their toxicities including osteonecrosis of the jaw and (potentially life threatening) hypocalcaemia and/or hypophosphataemia.
Data derived from controlled clinical trials form the prerequisite on which the status of approval, the approved indications and also the availability of a certain substance may prompt the treating physician to consider it within his or her repertoire based on his or her available knowledge and experience in the diagnosis, treatment and assessment of RA.
Each drug's originally approved indication(s) was counted only once for each comparison, even if the drug featured approvals of multiple supplemental indications.
Fewer supplemental approvals for new indications than originally approved indications were supported by trials using active comparators (30% (41/136) for supplemental indications versus 45% (90/201) for original indications; P=0.007), and more were supported by placebo controlled studies (57% (77/136) versus 42% (85/201); P=0.01) (table 3).
By contrast, similar rates of clinical outcome endpoints were used by efficacy trials forming the basis of approval for new indication supplements and those supporting originally approved indications (32% (44/137) versus 39% (78/202); P=0.22) (table 4).
Objective To characterize the types of comparators and endpoints used in efficacy trials for approvals of supplemental indications, compared with the data supporting these drugs' originally approved indications.
Finally, for each supplemental indication approval, we used the same classification frameworks to evaluate the characteristics of the major efficacy trials supporting the drugs' originally approved indications.
The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications.
DILI remains the major adverse drug event that leads to termination of clinical development programs and regulatory actions including failure for marketing approval, restricted indications, and withdrawal from the marketplace.
