Industry calls for flexibility in FDA’s pediatric measurement guidance

Regulatory NewsRegulatory News | 09 January 2023 |  By 

A pharmaceutical trade group and several drugmakers urged the US Food and Drug Administration (FDA) to take a more flexible approach in its guidance on pediatric measurements in clinical trials and questioned whether 12 months is sufficient to provide meaningful information for growth and development.
 
These comments were made in response to the agency’s call for feedback on the draft guidance, which outlines ways sponsors can measure pediatric growth consistently in clinical trials for drugs used to treat both rare and common diseases. (RELATED: FDA draft guidance aims to ensure accurate measurements of pediatric growth, Regulatory Focus 31 October 2022)
 
The guidance, issued jointly by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) address the collection of growth measurements such as weight, linear growth, and in certain cases, head circumference.
 
Industry objects to prescriptive requirements
 
The agency received seven comments on the guidance, with most expressing concern that the guidance places an undue burden on industry.
 
The Biotechnology Innovation Organization (BIO) wrote that the guidance “could be interpreted to be prescriptive” in specifying the tools used to measure growth and development. For example, the draft specifies that orchidometers can be used to measure genital changes in males and digital scales to assess weight.
 
“These tools may not be readily available in sites with fewer resources, especially in underserved communities,” states BIO. “We suggest that the guidance clarify flexibility around what tools may be used to avoid unintended consequences, i.e., creating challenges to enrollment of a greater population of patients from such communities.”
 
Bristol Myers Squibb (BMS) concurred, stating the guidance places an “undue burden” on site participants by requiring the calibration and measurement of instruments, as well as a provision stating that site visits and growth measurements should be scheduled at the same time of day, unless otherwise justified.
 
Otsuka also took issue with the scheduling provision. “Site visits for pediatric patients are often long and burdensome and need to fit into the patient’s schedule to minimize any absence from school and after-school activities,” states the company. “While consistent timing of event would be ideal, Otsuka suggest that the impact of rigid timing would negatively affect data collection outweighing the value of consistency.”
 
BIO suggests additional measurements
 
BIO also suggested the guidance offer more options for measuring patients with specific diseases associated with disproportionate growth, such as Marfan syndrome and skeletal dysplasia. These measurements could include arm span, sitting height and upper segment to lower segment ratio. Such an expansion, said BIO, would “strengthen the document.”
 
The group also suggested FDA expand on how dual-energy X-ray absorptiometry scans (DXA) can be used to measure growth. For example, DXA lumbar spine measurements “can provide reproducible measures of bone mineral content (BMC) and areal bone mineral density (aBMD) for infants and young children 0-5 years of age.”
 
12-month measurements
 
BIO questioned whether 12 months is sufficient to provide “clinically meaningful” information on growth and development; Otsuka and BMS concurred. The guidance specifies that sponsors collect and record growth measurements for a minimum of 12 months and to “discuss alternative trial durations with the appropriate review division and consider any potential safety concerns related to the drug for the intended patient population.
 
Otsuka also inferred that longer-term safety assessments may be needed to support a new drug’s safety in the pediatric populations, and Novartis said that 12 months should be the minimum duration of collecting and recording growth.
 
Otsuka objects to total disrobing
 
Otsuka also took issue with a provision that pediatric patients remove all clothing including shoes and socks during weighing. “Older children may be embarrassed by the removal of clothing discouraging their participation in trials. In particular, this could be disruptive to the participation of children with low or high BMIs, impacting he diversity of the trial population.”
 
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Tags: FDA, pediatric, trials

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