Core Viewpoint - The article discusses the challenges and considerations surrounding off-label drug use in pediatric patients, particularly for rare diseases, emphasizing the need to alleviate physicians' concerns regarding prescribing practices [1][3][6]. Group 1: Physician Concerns - Physicians are often conservative in their prescribing practices, especially for vulnerable populations like children, due to ethical and legal risks associated with off-label drug use [2][3]. - A significant percentage of doctors in Turkey and the U.S. avoid high-risk treatments, with estimates suggesting that around 50% of Chinese doctors may do the same, particularly in pediatric cases [1][2]. Group 2: Off-Label Drug Use - Off-label drug use is defined as using medications beyond the indications approved by regulatory authorities, which can include different dosages, routes of administration, or patient populations [3][5]. - There are two main categories of off-label drug use in pediatric rare diseases: high-cost innovative drugs and older, less expensive medications that may still provide benefits for rare conditions [4][5]. Group 3: Regulatory and Policy Framework - Recent guidelines and expert consensus have been developed to standardize off-label drug use in pediatric rare diseases, although there are still gaps in the regulatory framework [5][6]. - The National Health Commission has reiterated support for necessary off-label drug use, but reimbursement for such uses remains a challenge, as they are not typically covered by basic medical insurance [6][7]. Group 4: Research and Evidence - The expansion of drug indications for pediatric use often relies on real-world evidence, which is difficult to accumulate if physicians are hesitant to prescribe [3][8]. - Clinical trials for pediatric drugs face ethical challenges, leading to a reliance on adult data for pediatric applications, which complicates the approval process for new indications [7][9]. Group 5: Future Directions - There is a need for more patient-centered clinical trials to enhance data collection for pediatric rare diseases, as current methods often yield insufficient participant numbers [9][10]. - The industry is exploring innovative approaches to gather real-world evidence to support the expansion of drug indications for children, particularly in the context of rare diseases [9].

Core Viewpoint - The article discusses the challenges and considerations surrounding off-label drug use, particularly in pediatric patients with rare diseases, emphasizing the need to alleviate physicians' concerns regarding prescriptions [1][3][7]. Group 1: Physician Concerns - Physicians are hesitant to prescribe off-label medications due to concerns about ethical and legal implications, especially when treating vulnerable populations like children [2][4]. - A significant percentage of doctors in Turkey and the U.S. avoid high-risk treatments, with estimates suggesting around 50% in China, particularly for pediatric cases [2][3]. - The lack of evidence-based data for pediatric medications exacerbates physicians' reluctance to prescribe off-label treatments [3][4]. Group 2: Regulatory and Policy Framework - The National Health Commission supports reasonable off-label drug use when no better treatment options exist, provided that informed consent is obtained from patients [3][7]. - Recent guidelines and expert consensus have been published to standardize off-label drug use for pediatric rare diseases, addressing the absence of established protocols [5][7]. - Despite supportive policies, off-label drug use remains outside the scope of basic medical insurance coverage, placing financial burdens on patients [8]. Group 3: Drug Development and Research - The development of pediatric medications is hindered by ethical constraints in clinical trials, leading to a reliance on adult data for pediatric applications [8][9]. - The process of expanding drug indications for children is complex, often requiring extensive real-world data to demonstrate safety and efficacy [9][10]. - The pharmaceutical industry shows limited motivation to pursue new indications for pediatric use, making investigator-initiated trials (IIT) crucial for supporting new indications [9][10].