The Challenges of Paediatric Clinical Trials

Drug development for paediatric treatment continues to face a number of hurdles which compromise the success of a clinical trial. Without developing new strategies, patient recruitment and retention will remain low and many clinical trials will be terminated before they even begin. Innovative changes to parental engagement and trial transparency have opened the door to the possibility of securing successful paediatric studies. 

Introduction

Paediatric studies are essential for advancing therapeutic treatment for developmental and acquired illnesses. Unfortunately, it remains an on-going challenge to develop innovative, accessible drugs for rare paediatric diseases due to challenges at the clinical trial stage, including recruitment and retention. 

Psychological trauma is a common occurrence with paediatric patients and one of the reasons for poor participant retention. The frequent hospital visits associated with uncomfortable, painful procedures result in a fear of the clinical environment. 

The problem with this is that typical subjects required for paediatric studies are often these patients who have yet to succeed with treatment. Patients who have already had many negative experiences associated within clinical settings are at risk for dropping out mid-trial. 

Paediatric cancer especially presents numerous challenges for drug development. One of the main targets for the pharmaceutical industry is the formulation of oral drugs. Unfortunately, small tablets are not easily tolerated by children, which is why drug companies are constantly investigating new, easier ways of administration. 

The recruitment of children in clinical trials is invaluable due to their unique metabolic pathways, organic function, and physiology. Hence, paediatric studies are important to accurately represent the pharmacokinetic action of drugs within children to optimise their efficacy.

Nevertheless, due to various factors including unpleasant procedures, repeated hospital visits and side effects, patient retention remains an issue. Patient recruitment is also difficult due to ethical consideration of whether the subject understands the trial and how consent is validated. 

As a result, this greatly impacts the development of effective therapeutics for paediatric indications. New strategies are required to overcome these barriers, and improve the number of successful paediatric studies in order to support drug development.

Consent 

Informed consent is one of the most critical parts of clinical trial recruitment and can be especially challenging in paediatric recruitment. The Medicines for Human Use (Clinical Trials) Regulations prohibit children under the age of 16 from giving consent to take part in a Clinical Trial of an Investigational Medicinal Product (CTIMP). 

The only people who can give consent on behalf of children are the parent ( someone with parental responsibility); personal legal representative; professional legal representative (e.g. doctor responsible for the medical treatment). 

The clinical organisation is obligated to ensure that the parent or legal representative understand the following: “they are being asked to give consent on the behalf of the child/young person; the objectives, risks and inconveniences of the trial and the conditions under which it is to be conducted; have been informed of the right to withdraw the child / young person from the trial at any time; have a contact point where further information about the trial can be obtained”.

How are children recruited for clinical research?

While the children are the individuals taking part in the clinical trial, the burden of participation falls across the entire family. Transport to and from study visits and the completion of diary entries require the presence of a parent/caregiver to assist the child as best they can. In addition, some clinical trials require long-distance travel which can impact general day to day life for parents, balancing work with travel and care for other family members. 

Concerns surrounding these factors can comprise paediatric recruitment and derail a clinical trial before it has even begun. 

A 2012 study investigated the consent and recruitment strategies for paediatric trials, in the hope of identifying specific issues which need to be addressed urgently. It was found that out of the 300 paediatric trials investigated, the most notable reported shortcomings included: how families were recruited into the trial, who obtained consent and/or assent and how, who trial information was directed to, whether incentives were used and sufficient data to determine if the recruitment target was achieved.

Three key principles have been suggested to address some of the many issues that comprise paediatric clinical trials, and consequently support the smooth running of paediatric clinical trials:

Principle 1: Educate and Inform 

• Making sure parents fully understand why the drug is being investigated, why their child is being considered, and clarifying the health benefits vs risks. The aim of this is to ease some of their worries with regards to understanding the purpose of the clinical trial. Once enrolled in a study, parents need to be reassured that their child will receive optimal care. 

• Appropriate educational material should also be created to allow children to help make informed decisions as active participants in the clinical trial. 

• Ensuring there is a professional, accessible site for parents to use for information. A clear, but detailed website can help to educate users and understand the clinical research a little more.  

Principle 2: Ongoing Engagement

• Age-appropriate tools are important to help educate children, in order to make them feel more comfortable and involved in the study. Understanding how to engage different groups of patients is important, especially given they can be so different in age, indications and patient setting. For example, adolescents require more “direct, clear, honest, peer-to-peer communication… like social media”. This age group is typically very independent and responds well to digital engagement. 

Principle 3: Appreciation

• Demonstrating appreciation can have a huge impact on other clinical trials requiring paediatric patients. Newsletters, comfort items, and milestone awards for study accomplishments can create a positive trial experience, and help patients/families become strong advocates for research participation. 

A more recent study in 2017 identified the lessons learned on recruitment and retention in hard-to-reach families in a phase III randomised controlled trial of preparatory information for children undergoing general anaesthesia.

The study found that the retention rate was 83-85.5% at follow up time points up to 3.5 weeks following recruitment. Some insights were made with regards to how this was accomplished, which included ensuring continuity of care; determination to connect via telephone; valuing families’ time; and close monitoring of appointment date changes. This supports the positive impact of targeted engagement with patients and their families, demonstrating that the clinical organisation has the patient’s best interest at heart. 

Charlotte Di Salvo, Editor & Lead Medical Writer
PharmaFeatures