The pharmaceutical industry is highly competitive. The news often highlights the cost of coming to market and the race to reach the market first in order to recoup the development costs. Timelines for completing clinical trials are often mentioned as key drivers for sponsors, which is understandable given the large financial investment to bring a new treatment to market. The last two decades have seen the introduction of pediatric legislation that improves the scope and quality of pediatric drug development. This has led to an increase in the number of pediatric clinical trials being conducted, but its impact on the number of new drugs approved specifically for the pediatric population has been limited. The increase in trials has also lead to increased competition for a limited patient pool. This results in numerous trials taking longer or failing to complete due to poor design or an inability to recruit. We must consider stepping back and looking at ways to collaborate with all stakeholders to ensure that both trials and the marketed product meet the patients' needs.
Trials will not be successful without patients' participation. Looking at how we can 'recruit' patients to a trial must go beyond which trial wins the patient's attention. 'Competition' for patients is even more acute in pediatric research. In actuality, patients should be considered stakeholders and partners in the drug development process if we are to move towards collaborating with them and patient advocacy groups (PAG's). This will allow trial designs to meet the patients' needs. Patient-focused trials have been shown to improve recruitment, compliance, and retention, resulting in more robust trial results and quicker trial completion, ultimately reducing development costs and time¹. PAG's such as the International Children's Advisory Network (iCAN), a worldwide consortium of children's advisory groups, provide a platform for children and families to have their voices heard in pediatric clinical research.
Sites are another key stakeholder in the drug development process. By establishing working partnerships, we can focus on what can be done at the site level to improve the clinical trial experience. Sites and investigators collaborate through consortia, which is seen in oncology. For example, with POETIC, a network of 10 US and Canadian leading academic medical centers, focused on pediatric and young adult cancer patients with pediatric clinical trials experience. Sites are also working closely with PAG's. The Pediatric Trials Network (PTN) has established a partnership with iCAN. They aim to engage with patients and their families, gathering feedback on trial designs and patient materials for research being conducted by PTN. Such groups provide educational resources to support patients, developed through working with them and their families.
Sponsors can struggle with the development of patient-reported outcomes (PROs), particularly for pediatric or rare disease trials due to small patient numbers, the challenges of proxy PRO completion, and high failure rates. The Patient Reported Outcome Consortium was set up in 2008 by the Critical Path Institute, in cooperation with the FDA and the pharmaceutical industry, to allow for collaboration to develop qualified disease specific PRO's. The SISAQOL consortium² has developed international standards for quality of life (QoL) measures in cancer, an area where PRO quality is suboptimal, to help standardize analysis of PROs and determine more consistent and comparable QoL results for clinical trials³.
Collaboration is also important at the pre-competitive stages, including pre-discovery research, such as biomarker identification and screening platforms, as well as drug discovery, such as target identification and lead optimization, and pre-clinical. This has been highlighted with the recent RACE for Children Act where determining at a pre-clinical level if a drug has potential to treat pediatric cancers will be key to moving the right drug candidates to the clinical space. The set-up of consortia, such as the Pediatric Preclinical Testing Consortium (www.ncipptc.org) and the ITCC P4 platform (www.itccp4.eu), allows for developing reliable pre-clinical testing models and is a key step. Collaboration with drug developers will assist developers and regulatory agencies in prioritizing certain drugs or drug targets that are most likely to be clinically active against pediatric cancers.
Through improved collaboration across all stakeholders –such as sponsors, patients, sites, and/or regulators – we should aim to improve the trial experience for patients while accelerating the drug development process.
Ultimately, this can result in the quicker delivery of better treatments to patients, especially those for which there are unique challenges and great need – such as pediatric patients.
¹ Levitan et al, Assessing the Financial Value of Patient Engagement: A Quantitative Approach from CTTI's Patient Groups and Clinical Trials Project. Therapeutic Innovation & Regulatory Science 2018, Vol. 52(2) 220-229
³ International standards for the analysis of quality-of-life and patient-reported outcome endpoints in cancer randomised controlled trials: recommendations of the SISAQOL Consortium, Corneel Coens*, Madeline Pe*, Amylou C Dueck, et al, for SISAQOL. Lancet Oncol 2020; 21: e83–96