Lack of control groups and low infant participation

In a recent study published in Pediatric Research, researchers performed a scoping evaluation of data from clinical trials addressing high-risk pediatric medical devices used in children.

Study: Evidence from clinical trials on high-risk medical devices in children: a scoping review. Image Credit: Sai Thaw Kyar/Shutterstock.com

Background

Medical equipment is essential in the diagnosis and treatment of pediatric disorders; however, achieving European regulatory standards for clinical assessment might be difficult due to small patient numbers, unusual occurrences, and varied demographics.

Ethical difficulties, parental concerns, and increased financial regulatory expenses offer hurdles, with the pediatric age range having a poor possibility of attaining benefits on investment.

About the study

In the present study, researchers from the Coordinating Research and Evidence for Medical Devices (CORE-MD) initiative examined clinical trial data on using hazardous medical-grade devices in children. They investigated clinical trial techniques and designs that used medical devices in the high-risk category in children as the study intervention.

The researchers identified and described approaches in this research field by methodically summarizing published clinical data on hazardous medical devices, specifically accessible clinical trial evidence for children.

Databases such as Embase and Medline were searched between January 1, 2017, and November 9, 2022, for relevant records published in English.

The study included trials conducted for devices used in diabetology, cardiology, surgery, and orthopedics among individuals aged below 21 years, including neonates (birth to the initial four weeks), infants (from 29 days to two years of age), children (between two and 12 years of age), and adolescents (between 12 and 21 years of age), with conditions requiring medical devices.

The study comprised clinical trial findings on high-risk medical devices in children, including pre- and post-market clinical studies.

Observational studies, systematic reviews, conference abstracts, editorials, commentaries, book chapters, and letters were excluded from the analysis. There were no restrictions concerning the study setting or medical device indications. 

Mixed-population research, including children as well as adults, was also included. There were studies on class IIb and III medical devices under the European Medical Device Regulation (MDR) and class III medical devices under the Food and Drug Administration (FDA).

Based on MDR regulations, the high-risk category of devices includes class IIb active ones and class III implanted ones used to remove or administer medical substances from the human body.

Based on the FDA, the category included class III items implanted to support or sustain life or entail a potentially unreasonable disease or injury risk.

The team focused on medical devices listed in FDA sources such as the Premarket Approvals (PMA) database (as of February 2020); Yearly Reports to the Congress authorities on the Premarket Authorization of Pediatric Usage of Medical Devices, including authorized Humanitarian Device Exemption (HDE), and PMA applications (between 2008 and 2017); and the HDE database (between 2018 and June 2022).

The study outcomes included country; unicentric or multicentric; study design (such as controlled clinical trials, crossover trials, and one-arm interventional studies); sample population and the percentage of pediatric individuals; characteristics of the target population, such as age and sex; device type and indication; assessed study outcomes; approving regulatory bodies; and funding.

Two researchers independently screened the full-text records, and disagreements were resolved by discussion or involving a third researcher. Descriptive statistics were used for the analysis.

Results

A total of 1,692 records were screened, of which only 99 trials were considered for analysis. Most trials were performed in multicenter settings (65%), of which 73% were conducted in a single country, whereas 27% included multinational participants.

Most trials were conducted in Europe (35%) and North America (38%), and they evaluated medical device use in diabetology (88%) and cardiology (12%), including insulin pumps, glucose monitoring devices, and closed-loop systems.

Most trials (61%) included only individuals under 21 years, whereas 39% had adults and children, with 52% (median) pediatric individuals. Thirty-eight percent of trials were randomized controlled trials (RCTs).

Other study designs included crossover trials (20%) and before-and-after analyses (or baseline-controlled trials, 21%). Among RCTs and crossover trials, 13% were blinded.

Most trials (64%) included less than 100 individuals. Among problems including individuals aged below 21 years only (60 trials), the sample population (median) comprised 48 individuals. Safety (73%), effectiveness, and efficacy (79%) were the most frequent outcomes, with patient-documented outcomes assessed in only 24% of the included trials.

Usability was examined only for diabetology-related devices. Among the trials, 32% were funded by industry, and 43% received partial funding (devices provided by the industry at no or discounted cost).

Implications

Overall, the study findings highlighted the difficulties in conducting randomized clinical trials on high-risk medical devices for children, which frequently lack a control or comparator group.

These findings may aid health authorities in developing realistic evidence-level standards to support device conformity certification in Europe. To decrease bias, improvements include combining patient-reported outcomes and using a physician-initiated, industry-sponsored research approach.

Implementing the International Organization for Standardization (ISO) 14155 standard and mandating sponsors publish clinical investigation results can also assist in preventing any bias.

The findings may assist regulators and authorities in developing feasible and context-specific standards for clinical evidence supporting device compliance, thus ensuring the safety and continuous availability of critical technologies for treating ill children.