Tag Archives | Medicines for Children

Making Real-World Evidence (RWE) Work for Kids

The increased attention given to Real-World Evidence is a welcome development

The National Academies of Science held a workshop last October, “Real-World Evidence Generation and Evaluation of Therapeutics—A Workshop”, bringing together key thinkers to examine opportunities and challenges for incorporating real-world evidence into evaluation of medical products. Regulatory experts and FDA scientists followed-up with a cogent discussion of RWE and its use in the regulatory setting published in the New England Journal of Medicine, “Real-World Evidence — What Is It and What Can It Tell Us?” They reported that “the FDA is developing guidance on the use of ‘real-world evidence’ — health care information from atypical sources, including electronic health records, billing databases, and product and disease registries — to assess the safety and effectiveness of drugs and devices.”

Real-world evidence and the regulatory process

NAS workshop reviews RWE

Kids stand to benefit

Real-world evidence is of special importance to children because we can’t always conduct randomized clinical trials in pediatric populations. Real-world evidence, from large databases, electronic health records, and similar sources, may be the only evidence we have about medications or devices used by children. All the more reason to make sure that real-world evidence meets the unique needs we have when studying children: adequate sample sizes for all age sub-groups, critical data such as birth date, birth weight, and gestational age, ability to link to parental (and even sibling) data, and linkage with school performance metrics.

As efforts increase to address the challenge of developing high-quality RWE, we must consider and address the special considerations and challenges in using RWE to answer questions about the effects of medications in children. Asking these questions now will ensure that advances in the use of RWE will benefit children as well as other sectors of the population.

See Tamar Lasky’s editorial in the journal Drugs – Real World Outcomes, “In the Real-World, Kids Use Medications and Devices”.

Pediatric Pharmacoepidemiology at ICPE 2017 Annual Meeting

For the third year, the ISPE annual meeting (ICPE 2017 Montreal) will offer the pre-conference course in Pediatric Pharmacoepidemiology.

Mark your calendars for Sunday, August 27, 2017 (register here).

Brief Overview of Course

The increasing use of medications by children and the history of excluding children from clinical trials have created the need for pediatric pharmacoepidemiology, a sub-specialty within pharmacoepidemiology. Unique challenges in studying children, accessing data, defining outcomes, and designing studies require specialized methodologic skills and operational approaches. This half-day course will introduce participants who have a good understanding of pharmacoepidemiology to the specialized methodologic and operational approaches used to study medications in children.

Pediatric Pharmacoepidemiology

Age is not a simple variable when studying children

Educational Objectives

The course will be taught in an interactive format with ample opportunities for questions and discussion. Regulatory issues around use of medications in children will be highlighted throughout the course. Participants will gain an understanding of key issues in pediatric pharmacoepidemiology including:

  • An overview of pediatric pharmacoepidemiology and how it differs from pharmacoepidemiology in older age groups
  • Study design and databases to monitor safety
  • Defining, measuring and validating outcomes in pediatric pharmacoepidemiology
  • Variables critical to pediatric pharmacoepidemiology such as month of birth, seasonality, growth and development

Target Audience

ICPE attendees interested in gaining a basic understanding of the need for and approaches to pediatric pharmacoepidemiology.

Course Faculty/Presentations

  • Tamar Lasky, PhD Owner, MIE Resources Why Pediatric Pharmacoepidemiology? Age Sub-groups in Children: Methodologic Considerations
  • Alan Kinlaw, PhD Post-doctoral Research Fellow, Sheps Center for Health Services Research, University of North Carolina at Chapel Hill Leveraging granular birthdate information for studies of young children
  • Rachel E. Sobel, DrPH Senior Director, Epidemiology, Worldwide Research and Development / Pfizer Inc. Monitoring Drug Safety: Study Design, Data Sources and Case Study
  • Timothy Beukelman, MD, MSCE Associate Professor of Pediatrics, Division of Pediatric Rheumatology, Department of Pediatrics, University of Alabama at Birmingham The Need for Validation in Pediatric Outcomes
  • Daniel B. Horton, MD, MSCE Assistant Professor of Pediatrics and Epidemiology, Rutgers University Growth and Development: Variables of Particular Importance in Pediatric Pharmacoepidemiology



Improving Medicines for Children in Canada

“Studying medicines in children is always possible and is in their best interests”

A sentiment that can’t be repeated often enough.

The Council of Canadian Academies just released their report, Improving Medicines for Children in Canada, and while the title indicates a focus on Canada, much of the report is relevant to goal of improving medicines for children everywhere.

Children have historically been excluded from clinical trials and drug research to protect them from the risks of research.

As a result, there is a lack of information about medicines and how they affect children at different ages and stages of development. Throughout, the panel stresses the importance of including children in research,

The assumption that children must be protected from research is misguided. Children should be protected through research. Despite the many challenges to research with children, a range of methods and designs are increasingly accepted as ethically and scientifically sound. Demonstrating safety and efficacy of a medicine in studies with children is always feasible and desirable. It is now globally recognized that the medical community, the pharmaceutical industry, and regulatory agencies have an ethical responsibility to design, conduct, and report on high-quality studies of medicines in children.

Key findings

As with so much of the report, the key findings are applicable in the US, Europe and elsewhere. As they note,

  • Children take medications, many of which have not been proven safe and effective for their use.
  • Children respond to medications differently from adults; thus, medicines must be studied in children and formulated for children.
  • Studying medicines in children is always possible and is in their best interests.

The panel reviewed a comprehensive body of information and brings together relevant science from several disciplines. As such, it provides a cogent synthesis of the many issues around pediatric medication use. It begins with a description of the current environment and regulations, variation in children’s response to medications, issues around formulation, and covers current approaches to studying efficacy in children, monitoring and studying the safety of drugs used by children, and a thoughtful discussion around practices to support safe and effective products for children.

Off-label use

The overview of the current environment provides this useful chart summarizing different types of off-label practices, with examples of both the authorized (on-label) and off-label use.

Medicines for children

Off-label practices

Variability in response to medications

Chapter 3 includes this schematic of the factors affecting variability in children’s responses to medications.


Medicines for children

CCA schematic – drug response in children

They return to this issue in their conclusions, as they underscore the affect of human development from infancy to youth, and its affect on clinical pharmacology,

As children progress from infancy through to adolescence, a number of significant developmental changes occur. These changes impact how their bodies deal with medications (pharmacokinetics) and how medications, in turn, affect their bodies (pharmacodynamics). These factors cannot be accommodated by simply adjusting an adult dose. The physiological systems that process drugs change over time, with the most dramatic age-related physiological changes taking place during the first year of life. A newborn will respond to a drug differently than an adolescent will, and this variability in response is not a linear progression but rather a dynamic process dependent on age, weight, the drugs and conditions involved, and individual and environmental factors.

The report concludes with a fervent call to action,

Children’s right to health includes a right to medicines that are well-studied and approved for use in their age group. Children deserve timely and equitable access to safe and effective treatments and care, including participation in research.

The Expert Panel on the State of Therapeutic Products for Infants, Children, and Youth was chaired by Dr. Stuart MacLeod, Professor of pediatrics at the University of British Columbia in Vancouver.