Monday, July 10, 2017

Age Group in Pediatric, Perinatal or Preterm, and Geriatric Subjects

In a previous blog article, I discussed the “Pediatric use and geriatric use of drug and biological products”:
For Pediatric population: according to ICH guidance E11 "Clinical Investigation of Medicinal Products in the Pediatric Population", the pediatric population contains several sub-categories:
  • preterm newborn infants
  • term newborn infants (0 to 27 days)
  • infants and toddlers (28 days to 23 months)
  • children (2 to 11 years)
  • adolescents (12 to 16-18 years (dependent on region))
Notice that in FDA's guidance "General Considerations for Pediatric Pharmacokinetic Studies
for Drugs and Biological Products
for Drugs and Biological Products", the age classification is a little bit different. I am assuming that the ICH guidance E11 should be the correct reference.
Geriatric population:
Geriatric population is defined as persons 65 years of age and older. There is no upper limit of age defined.
Recently, I run into several studies where the age group needs to be further split.

Pediatric population can be further divided into 2-5 years old, 6-11 years old, and 12-16 years old.
This grouping of the pediatric population was used in a pharmacokinetic study in primary immunodeficiency patients in child. Per FDA’s request, the pediatric patients are further divided into groups 2-5, 6-11, and 12-16 years old. FDA asked that the study should contain subjects in each of the sub-groups so that the assessment can be made to see if the pharmacokinetics are consistent across different pediatric sub-groups (or at least there should be no obvious difference among these sub-groups).
An Open-label, Single-sequence, Crossover Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Subcutaneous GAMUNEX®-C in Pediatric Subjects With Primary Immunodeficiency
The age definition in perinatal period is much trickier. In a policy statement by Committee on Fetus and Newborn “Age Terminology Duringthe Perinatal Period”, various definitions of age are described:
  • Gestational age (or “menstrual age”) is the time elapsed between the first day of the last normal
  • menstrual period and the day of delivery
  • “Chronological age” (or “postnatal” age) is the time elapsed after birth
  • Postmenstrual age (PMA) is the time elapsed between the first day of the last menstrual period and birth (gestational age) plus the time elapsed after birth (chronological age). Postmenstrual age is usually described in number of weeks and is most frequently applied during the perinatal period beginning after the day of birth.
In clinical trials with pre-term babies, the study endpoints are usually defined based on the post-menstrual age (PMA). For example, in an article by Bassler et al “Early inhaled budesonide for the prevention ofbronchopulmonary dysplasia”, the primary outcome was a composite of death
or bronchopulmonary dysplasia at 36 weeks of postmenstrual age. While the study treatment will not be given until after the birth, 36 weeks of postmenstrual age is counted from the first day of the last menstrual period. For different babies, the chronological age or observation period (when the death or BPD event is observed) will be different depending on the actual gestational age.  

It can be illustrated in the following diagram.

  • Gestational age = birth date – the first day of the last normal menstrual period
  • Chronological age = assessment date or event date – birth date
  • Postmenstrual age = assessment date or event date – the first day of the last menstrual period
  • Postmenstrual age = gestational age + chronological age

Geriatric population can be further divided: 
In a study with Interstitial Lung Diseases (ILDs) in elderly patients, there are substantial number of patients with age >= 80 years old. The traditional definition of geriatric population using 65 years old as a cut point will not be sufficient. We end up further dividing the geriatric population into 65 - < 80 years old and >= 80 years old. We think this will provide more meaningful sub-grouping to assess the impact of the age group in ILD indication. 

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