The changing landscape of data monitoring committees-Perspectives from regulators, members, and sponsors.

Data Monitoring Committees (DMCs) are an integral part of clinical drug development. Their use has evolved along with changing study designs and regulatory expectations, which has associated statistical and ethical implications. Although there is guidance from the different regulatory agencies, there are opportunities to bring more consistency to address practical issues of establishing and operating a DMC. Challenging issues include defining the scope of DMC decisions, the regulatory requirements and expectations, the perceived independence of DMCs, the specific focus primarily on safety, etc. Wider use of adaptive clinical trial designs in recent years introduce additional challenges in terms of trial governance and the complexity of DMC activities. A panel comprised of clinical and statistical experts from across academia, industry, and regulatory agencies shared their experience and thoughts on the importance of these aspects and offered perspectives on the future of the DMCs. This paper documents the thinking from the panel session at the CEN-ISBS conference held in Vienna, Austria, 2017.

Temperature Imposed Sensitivity Issues of Hetero-TFET Based pH Sensor.

An underlapped hetero-structure electrolyte Bio-TFET for potential of hydrogen (pH) sensing has been presented in this article. Intersection charge density ( [Formula: see text]) near the substrate-oxide junction can be employed to represent pH value within the simulation. A feasible fabrication scheme for the proposed model is specified here. A detailed simulation is performed with an ATLAS device simulator to examine the efficiency of the projected sensor. The impact of pH alterations on device features akin to the drain current ( [Formula: see text]), threshold potential ( [Formula: see text]), sensitivity regarding voltage ( [Formula: see text]), and current ( [Formula: see text]) is examined. The effect of phosphate-buffered saline (PBS) concentrations on the pH buffer are also scrutinized. Moreover, the impact of the reference voltage and current ( [Formula: see text] and [Formula: see text]), and channel doping concentration ( [Formula: see text]) over [Formula: see text] and [Formula: see text] is analyzed methodically. Here, [Formula: see text] attains ≈100 mV/pH, which is superior to the Nernstian limit (59 mV/pH) and [Formula: see text] enhances nearly ten times per pH variation. Benchmarking is included to provide a quantitative assessment of the proposed model with the published literature. The impact of temperature on pH buffer, [Formula: see text], temporal drift parameters and sensitivities have been emphasized. Finally, the temperature-immunity aspect of the proposed Bio-HTFET based pH sensor is highlighted by comparing sensitivity parameter among state-of-the-art literature. Hence, the recommended pH sensor can be utilized as an outstanding substitute for the succeeding generation of biosensor applications.

Effectiveness of neurofeedback training, behaviour management including attention enhancement training and medication in children with attention-deficit/hyperactivity disorder - A comparative follow up study.

BACKGROUND: Attention Deficit/ Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental psychiatric disorders of childhood. Treatment of ADHD includes medications and Behavioural interventions. Neurofeedback, a type of biofeedback, has been found to be useful in ADHD. It helps patients to control their brain waves consciously. However, it is not yet conclusive if it is efficacious in comparison to behavioural management training and medication. AIM: To compare the efficacy of neurofeedback training, behaviour management including attention enhancement training and medication in children with ADHD. METHOD: Ninety children between 6 and 12 years with ADHD were taken and randomly divided into 3 treatment groups equally- neurofeedback, behaviour management and medication (methylphenidate). Conners 3-P Short Scale was applied for baseline assessment. The respective interventions were given and follow up was done at the end of 3 months by using Conners 3-P Short scale to assess the improvement in the symptoms. There were 6 dropouts, the final sample size was 84. RESULTS: The medication group showed the greatest reduction of symptoms in inattention, hyperactivity, executive functioning domain (core symptoms of ADHD). No statistically significant difference was observed between Neurofeedback and Behaviour Management in these domains. Learning problems improved in all three groups, neurofeedback being the most effective followed by medication. Both Neurofeedback and Medication groups showed similar effect which was higher than the Behavioural Management group in Peer Relation. CONCLUSION: Improvement in core ADHD symptoms have been observed with all 3 interventions with medication showing the greatest improvement Neurofeedback has been superior for learning problems. Thus, Neurofeedback can be an independent or combined intervention tool for children with ADHD in outpatient department of Psychiatry.

Aggregate Safety Assessment Planning for the Drug Development Life-Cycle.

The Program Safety Analysis Plan (PSAP) was proposed previously as a tool to proactively plan for integrated analyses of product safety data. Building on the PSAP and taking into consideration the evolving regulatory landscape, the Drug Information Association-American Statistical Association (DIA-ASA) Interdisciplinary Safety Evaluation scientific working group herein proposes the Aggregate Safety Assessment Plan (ASAP) process. The ASAP evolves over a product's life-cycle and promotes interdisciplinary, systematic safety planning as well as ongoing data review and characterization of the emerging product safety profile. Objectives include alignment on the safety topics of interest, identification of safety knowledge gaps, planning for aggregate safety evaluation of the clinical trial data and preparing for safety communications. The ASAP seeks to tailor the analyses for a drug development program while standardizing the analyses across studies within the program. The document is intended to be modular and flexible in nature, depending on the program complexity, phase of development and existing sponsor processes. Implementation of the ASAP process will facilitate early safety signal detection, improve characterization of product risks, harmonize safety messaging, and inform program decision-making.

Global Regulatory Landscape for Aggregate Safety Assessments: Recent Developments and Future Directions.

Notwithstanding successful harmonization efforts, the global regulatory framework governing product safety is complex and continually evolving, as evidenced by additional regional guidance and regulations. In this regulatory review, we provide an overview from both global and regional perspectives. A historical perspective, with a focus on recent developments, enables identification of important long-term trends, such as a shift from single-case medical review of serious adverse events to an interdisciplinary evaluation of aggregate data for the purpose of judging product causality and informing benefit-risk assessments. We will show how these trends lead to opportunities for closer interdisciplinary collaboration, for bridging the gap between preand postmarketing surveillance, and for a more proactive determination of patient populations with a positive benefit-risk profile for product use. We will conclude by pointing to ongoing and future work that seeks to provide specific solutions for ongoing aggregate safety evaluation.

Safety Reporting: It Can Enter the 21st Century-If We Let It.

This is a commentary about the evolution of safety reporting, the new FDA Draft Guidance on Safety Reporting and possible paths forward.

Tramadol versus clonidine in management of heroin withdrawl.

UNLABELLED: Opiod dependence is one of the leading psychiatric morbidities in India. The deaddiction centres are meager in number; stigma attached to admission in deaddiction centre is high and most addicts want outpatient treatment so that they do not miss daily wages. Several recent reports stated effectiveness of tramadol in treating opioid withdrawal. This study attempts to compare effectiveness of tramadol with clonidine in opioid withdrawal. METHODOLOGY: A total of 60 patients having heroin dependence were selected and out of them 30 got clonidine treatment and the other 30 got tramadol treatment. The clinical opioid withdrawal scale was used. STATISTICAL ANALYSIS: "t"-Test was used using SPSS (version-16) for comparison. RESULT: Tramadol was more effective in preventing sweating, restlessness, aches, runny nose, GI upset, yawning, anxiety and goose skin. i.e., Tramadol can be used effectively in opioid withdrawal in outpatient based treatment programme.