Table 2.

Barriers encountered and team strategies used

Barrier	Strategy
Translating findings
Lack of commercially available, neonate-safer drug formulation of longer-acting opioid (methadone or buprenorphine), which research had found to be superior to most common drug treatment (morphine)	Advocated for legislation and policy change to incentivize and facilitate pediatric drug development [24,30] Engaged pharmaceutical company to develop a neonate-safer formulation of longer-acting opioid (buprenorphine) Facilitated collaborations between funder and pharmaceutical company to support feasibility of clinical trial for the new formulation.
Conducting research for neonatal abstinence syndrome (NAS)
Legal and regulatory barriers
Food and Drug Administration (FDA) requirement for new drug formulation for research despite ongoing use in clinical care	Developed an alcohol-free liquid formulation using methadone powder for research purposes The alcohol-free product needed to be tested extensively by an independent laboratory approved by FDA prior to use in neonates
Transportation and storage restrictions for regulated study drug	Obtained Drug Enforcement Administration (DEA) approval to move methadone to trial sites
Mandated reporting requirements regarding illicit / recreational drug use of research participants, which undermined trust	Advocated for increased confidentiality protection for pregnant persons participating in research regarding opioid use disorder (OUD) and NAS by publishing an article with an FDA representative[28]
Recruitment challenges
Stigma and mothers’ concerns about potential negative side effects of study drug for neonate	Engaged obstetricians providing antenatal care to the mothers (a trusted source) to introduce the study and obtain informed consent. Added additional sites and expanded the inclusion criteria (e.g., including mothers who used illicit drugs during pregnancy) in order to enroll more subjects.
Controlled study design with narrow inclusion criteria (requiring mothers to be in an OUD treatment program or receiving an opioid for chronic pain treatment, but not using illicit drugs)
Funding environment
Episodic funding limited the ability to retain research staff between funding awards	Although individual research teams have limited ability to overcome this barrier, the team utilized no-cost study design and statistical guidance services supported by the local Clinical and Translational Science Award (CTSA) as a partial solution to continuity of research staff and projects