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1.  Independent data monitoring committees: Preparing a path for the future 
American heart journal  2014;168(2):135-41.e1.
Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and study conduct in randomized clinical trials (RCTs), but certain challenges regarding the utilization of IDMCs have developed. First, the roles and responsibilities of IDMCs are expanding, perhaps due to increasing trial complexity and heterogeneity regarding medical, ethical, legal, regulatory, and financial issues. Second, no standard for IDMC operating procedures exists, and there is uncertainty about who should determine standards and whether standards should vary with trial size and design. Third, considerable variability in communication pathways exist across IDMC interfaces with regulatory agencies, academic coordinating centers, and sponsors. Finally, there has been a substantial increase in the number of RCTs using IDMCs, yet there is no set of qualifications to help guide the training and development of the next generation of IDMC members. Recently, an expert panel of representatives from government, industry, and academia assembled at the Duke Clinical Research Institute to address these challenges and to develop recommendations for the future utilization of IDMCs in RCTs.
PMCID: PMC4181557  PMID: 25066551
2.  Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products: Workshop Summary Report 
The AAPS Journal  2010;12(3):371-377.
Modified release products are complex dosage forms designed to release drug in a controlled manner to achieve desired efficacy and safety. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current industry practices and regulatory expectations for demonstrating pharmaceutical equivalence and bioequivalence of MR products, further facilitating the establishment of regulatory standards for ensuring therapeutic equivalence of these products.
PMCID: PMC2895434  PMID: 20440588
bioequivalence; interchangeability; modified release; pharmaceutical equivalence; therapeutic equivalence
3.  Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration  
Objective To examine the risk of suicidal behaviour within clinical trials of antidepressants in adults.
Design Meta-analysis of 372 double blind randomised placebo controlled trials.
Setting Drug development programmes for any indication in adults.
Participants 99 231 adults assigned to antidepressants or placebo. Median age was 42 and 63.1% were women. Indications for treatment were major depression (45.6%), other depression (4.6%), other psychiatric disorders (27.6%), and non-psychiatric disorders (22.2%).
Main outcome measures Suicidal behaviour (completed suicide, attempted suicide, or preparatory acts) and ideation.
Results For participants with non-psychiatric indications, suicidal behaviour and ideation were extremely rare. For those with psychiatric indications, risk was associated with age. For suicidal behaviour or ideation and for suicidal behaviour only, the respective odds ratios were 1.62 (95% confidence interval 0.97 to 2.71) and 2.30 (1.04 to 5.09) for participants aged <25, 0.79 (0.64 to 0.98) and 0.87 (0.58 to 1.29) for those aged 25-64, and 0.37 (0.18 to 0.76) and 0.06 (0.01 to 0.58) for those aged ≥65. When age was modelled as a continuous variable, the odds ratio for suicidal behaviour or ideation declined at a rate of 2.6% per year of age (−3.9% to −1.3%, P=0.0001) and the odds ratio for suicidal behaviour declined at a rate of 4.6% per year of age (−7.4% to −1.8%, P=0.001).
Conclusions Risk of suicidality associated with use of antidepressants is strongly age dependent. Compared with placebo, the increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents. The net effect seems to be neutral on suicidal behaviour but possibly protective for suicidal ideation in adults aged 25-64 and to reduce the risk of both suicidality and suicidal behaviour in those aged ≥65.
PMCID: PMC2725270  PMID: 19671933
4.  Blood pressure as an example of a biomarker that functions as a surrogate 
The AAPS Journal  2006;8(1):E146-E152.
There are many important uses of biomarkers in drug development. An area of particular interest is the use of biomarkers as surrogate end points. Only a small minority of biomarkers are established surrogate end points. Blood pressure is an example of a surrogate end point accepted by both clinicians and regulators. It was a plausible surrogate because of the large epidemiologic databases demonstrating a correlation between elevated blood pressures and adverse cardiovascular outcomes. That plausibility has been supported, however, by the numerous placebo-controlled outcome studies evaluating several pharmacologically distinct agents that showed an effect on stroke and coronary heart disease outcomes from lowering blood pressure.
PMCID: PMC2751433  PMID: 16584122
biomarker; surrogate endpoint; blood pressure

Results 1-4 (4)