Uncontrolled trials formed the basis of approval for 34% (22/65) of expanded population supplements, and nine (14%) of these supplemental approvals had no clinical efficacy trials.
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).
"We expect a major theme for the biotech sector to be new product and supplemental approvals for the industry".
She added that Kesselheim's findings that less than a third of supplemental approvals were supported by clinical studies was "appalling".
Conclusions Wide variations were seen in the evidence supporting approval of supplemental indications, with the fewest active comparators and clinical outcome endpoints used in trials leading to supplemental approvals that expanded the patient population.
Trials using clinical outcome endpoints led to approval for 32% (44/137) of supplemental approvals for new indications, 30% (28/93) of modified indication approvals, and 22% (14/65) of expanded population approvals (P=0.29).
Yet in the case of supplemental approvals for pediatric use, such studies will lead to six months of additional market exclusivity under the Best Pharmaceuticals for Children Act, which can be extremely lucrative for the sponsor.
Thirty per cent (41/136) of supplemental approvals for new indications were supported by efficacy trials with active comparators, compared with 51% (47/93) of modified use approvals and 11% (7/65) of approvals expanding the patient population (P<0.001), almost all of which related to pediatric patients (61/65; 94%).
Orphan drugs had supplemental approvals for 40 non-orphan indications, which were supported by similar proportions of trials using active comparators (28% (11/40) for non-orphan supplemental indications versus 24% (10/42) for original orphan indications; P=0.70) and clinical outcome endpoints (25% (10/40) versus 31% (13/42); P=0.55).
Cubist Pharmaceuticals shares surged 20% last Friday after the company said it received supplemental FDA approval of anti-infective Cubicin.
For each supplemental indication approval, we determined its primary therapeutic area by consensus.
