Role of patient-reported outcomes and other efficacy endpoints in the drug approval process in Europe [2008-2012]

The present study aimed at systematically reviewing the role and extent of patient-reported outcomes [PROs] usage within the package of scientific evidence considered for marketing authorization [MA]. All regulatory information published by the European Medicines Agency [EMA] for products authorized between January 2008 and December 2012 and appearing in the European Public Assessment Report [EPAR] database was examined for efficacy endpoints. The endpoints here considered included: PROs, clinician reported outcomes [CROs], and laboratory reported outcomes [LROs]. LROs were the most frequently reported endpoints. Out of the 180 products here selected, 99 [55%], 67 [37%], and 30 [17%], respectively, used LROs, CROs and PROs as primary endpoints [PEs]. PROs as any endpoints were used in 82 [46%] products. Out of these, PROs were documented as PE in 30 [37%], with 27 [33%] products having used PROs both as primary and non-PEs. PRO usage was most frequently identified with nervous system and antineoplastic agents. During the study period, the use of all the three types of endpoints appeared to be static. Both the regulatory bodies and the industry should ensure complete and clear reporting of all endpoints used, including PROs, to improve transparency

Ruboxistaurin for the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review of Randomized Clinical Trials

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. Protein kinase C (PKC) inhibitor's has been thought to be a potential disease modifying drug's in DPN as it slows or reverse neuropathy's progression. To assesses the efficacy and safety of ruboxistaurin on the progression of symptoms, signs, or functional disability in DPN. METHODS: A systematic review of the literature databases like PubMed, ProQuest, EBSCO, EMBASE, and Cochrane Central was performed up to August 2012. We included randomized controlled trials (RCTs) comparing PKC inhibitor ruboxistaurin (RBX) with control and lasting at least 6 months. Our primary outcome measure was change in neurological examination, measured by neurological total symptom score (NTSS) and vibration detection threshold (VDT). Secondary outcome measures were total quality of life (QoL), skin microvascular blood flow and others. RESULTS: Six RCTs were included in review. Change in neurological function assessed by NTSS was reported in six studies, out of which significant difference between the RBX and placebo group seen in four studies favouring treatment group while remaining two studies reported no significant difference. VDT was assessed in only one study in which no significant difference seen between RBX and placebo group. Two studies reported significant improvement in QoL data. Safety data was reported in only two studies in which none of side effect was related to RBX. CONCLUSION: RBX had effects on DPN in some studies, but the evidence is not enough for meta-analysis and firm conclusion.

Ruboxistaurin for the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review of Randomized Clinical Trials

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. Protein kinase C (PKC) inhibitor's has been thought to be a potential disease modifying drug's in DPN as it slows or reverse neuropathy's progression. To assesses the efficacy and safety of ruboxistaurin on the progression of symptoms, signs, or functional disability in DPN. METHODS: A systematic review of the literature databases like PubMed, ProQuest, EBSCO, EMBASE, and Cochrane Central was performed up to August 2012. We included randomized controlled trials (RCTs) comparing PKC inhibitor ruboxistaurin (RBX) with control and lasting at least 6 months. Our primary outcome measure was change in neurological examination, measured by neurological total symptom score (NTSS) and vibration detection threshold (VDT). Secondary outcome measures were total quality of life (QoL), skin microvascular blood flow and others. RESULTS: Six RCTs were included in review. Change in neurological function assessed by NTSS was reported in six studies, out of which significant difference between the RBX and placebo group seen in four studies favouring treatment group while remaining two studies reported no significant difference. VDT was assessed in only one study in which no significant difference seen between RBX and placebo group. Two studies reported significant improvement in QoL data. Safety data was reported in only two studies in which none of side effect was related to RBX. CONCLUSION: RBX had effects on DPN in some studies, but the evidence is not enough for meta-analysis and firm conclusion.