CLINICAL RESEARCH

Accelerating global paediatric recruitment and retention – strategic and tactical approaches

Janet Jones PhD, Director, Global Patient Access and Retention, Kendle

Patient recruitment is at the core of all clinical projects and can be influenced by a variety of factors: protocol design, investigator motivation, competing studies, and patient willingness to join a study. A good recruitment and retention strategy is planned, tailored and fully integrated into the workings of the clinical study team. In addition, it has the flexibility to take into account the needs of countries and sites, applying the most appropriate approaches to meet different therapeutic areas, study phases and details of the study design. This is not ‘one solution fits all’, but there are some elements that apply to every study. In this article we examine the common elements and apply them to the conduct of global paediatric studies.

Paediatric studies are dependent on the strength of the relationship between the site and the patient and their family. Therefore, our patient recruitment planning has to be site focused and based on helping the site to connect with their own patients. It is important to motivate paediatric sites and make interaction with their patients as seamless as possible. This needs to be a holistic approach, involving the whole study community (sites, sponsor, study team, patients and parents/guardians) and will be successful only by putting the patient at the heart of our thinking. In the case of paediatric studies, there are two patients to be considered, the child and their parent. The following are the key elements for success:

• Detailed feasibility and planning to select the right countries that can perform the study in line with the standard of care for the indication, and then selecting the right sites with the required patient access, motivation and experience;
• Group effort involving the clinical trial commodity (experienced professionals, parent and the child);
• Protect the child from harm, respect autonomy and provide the child and their parents with good information to support the consent/assent process;
• Age and child-targeted materials;
• Appropriate approaches for the specific population, taking into account the therapeutic area, disease and cultural sensitivity.
• Select sites that are sensitive to the needs of children and their family.

Globally, there is growing interest in conducting studies by established paediatric investigators. Paediatric sites are unique in the way in which they are part of established referral networks with other paediatric hospitals and have considerable experience conducting clinical trials. However, with recent changes in paediatric legislation this is becoming an increasingly crowded and competitive environment. As a result, studies are looking for more primary care investigators. Therefore, we need to take a more global approach to identifying investigators and ensure we provide good support and training. Providing these sites with materials to assist parent and child awareness can have a positive impact on recruitment. Sites that are sensitive to the needs of the child and parents are the key. If sites are interested and committed to the study, they will work appropriately with the families.

Conduct feasibility to assess the countries with access to the required patient population

In many western countries the demographic pyramid is shifted toward an older population (shown in Figure 1 for both the United States and the United Kingdom), with similar profiles in other western countries and in Central and Eastern Europe. However, there are significant opportunities to find the required paediatric population in countries with a much larger young population, such as India, China and countries in Latin America. Latin America for example, has a population of 420 million, 30% of which are under the age of 14 years (130 million), which compares favourably with the 60 million in the U.S. (less than 20% of the population1). If the protocol matches the standard of care, there are many benefits to using these regions to access the paediatric population, provided that the sites are interested and patients can be given support and good information about the study and what their participation means.

Global country planning

In order to use the optimal mix of countries, it is important to plan the involvement of key countries and their recruitment campaigns from the beginning. The contribution of Latin America can be maximised by planning for the long start-up times of Brazil and Argentina and making sure that the sites have patients lined up ready to start when they get approval. Recent changes in legislation make India an increasingly popular country for studies, with relatively fast start-up times (provided the study has gained approval in another country and can be started under schedule B), high patient numbers and highly educated and motivated physicians.

 

Children are not small adults

If we are to help sites with their recruitment efforts, we need to understand how to communicate with them and ensure any messages are targeted to the child. These need to be tested on children, rather than what the sponsor/project team feels would interest a child, which is an easy mistake to make. There are two main areas of consideration:

• How do the children see their disease?
• What do they want/expect to get out of treatment, study participation and interaction with their healthcare professionals?

As shown in Figure 2, a child’s understanding of their disease as well as the way they respond to it will change significantly over time. Consequently, materials/approaches need to be adopted to meet these changing expectations. Furthermore, children have high expectations of their doctor and other healthcare professionals (Figure 3). These expectations are based on trust and empathy, and it is important to create educational and supportive materials that allow the child to develop trust with the study site. For example, in a global HIV study, it was important to make sure the child did not appear to be different to other children. Therefore, all study materials were low key and supportive measures were put in place, such as providing the study drug in a drink to take to school so that they did not need to take tablets in front of their peers. As many of the families were on a lower income, helping the family with travel to study visits was a key driver in recruitment and retention.

Equality and understanding

Often, children find it comforting to learn the terminology/procedures associated with their disease and treatment, becoming experts on their own illness. They want to feel they are treated as equals by medical and study staff and that:

• Doctors and nurses will tell them the truth if they ask for it, however frightening it may feel. If they’d rather not know too much, this wish will be respected too.
• Site staff will not be condescending and will use age-appropriate ways of explaining the study to them. If information is over simplified, it can make patients feel less than equal and may lead to mistrust.

Also, patients want to know the site staff understands their needs and the fear they feel when dealing with their disease, particularly if it is a serous disease such as cancer. Many paediatric patients are still at an age when they want to be accompanied by a parent throughout the entire experience, but the practical realities of modern life may not make this possible. Consequently, they want to know that:

• Site staff will do the very best to treat their disease and if this means there are significant side effects, these will be managed in a sensitive manner. Especially for younger patients who might not be fully aware of what is happening to them, an understanding and sympathetic approach can make patients feel more comfortable.
• Staff have a thorough understanding that children like routine, and if this can be maintained, it can be of great comfort to patients.

“I am not just my disease”

Many paediatric patients with a serious disease, such as cancer, feel their whole identity revolves around their cancer and being ill. In order to motivate them to engage in a trial, patients need to look to their future and what lies at the end of their illness. Depending on the age of the child, this vision of the future may be difficult for them to grasp, but emphasising that their illness is not the most important thing about them as a person is helpful. Boosting their self-esteem with positive reinforcement is extremely beneficial.

Determination

Having a serious illness can seem like a constant struggle, especially when paediatric patients are missing out on many aspects of normal life. Being different to other children is often hard, so the determination to get back to school, family and friends is very important. Patients want to know what goals they can reach towards a normal life, such as overcoming fatigue after chemotherapy and managing to spend some time at school. By providing patients with realistic expectations, site staff can help harness the determination of paediatric patients, making them work towards their treatment goals.

Engaging the whole study community

Helping sites with the consenting process is a key factor with paediatrics studies. Sites know the importance of consent, but often don’t realise the impact of the way key issues are being presented. The most successful paediatric sites have a good process for educating patients and are careful about the study messages they convey and the way that they communicate with children and families. Therefore, sites consistently utilise a range of materials to work through the consenting process and to provide children with something they can take away to consider in the comfort of their own homes. A successful format is to develop a child-focused interactive CD, which tells the story of the study and asks simple questions after each section to ensure understanding. This is supported by printed educational materials and clear visual study guidance to use when they are walking through the consent process.

Training healthcare professionals is an often-overlooked area, but can help to provide the study team with the specialist skills needed to deal with paediatric patients. In addition to providing the tools described above, training can take the form of providing play scenarios to explain the study requirements, and presentations by adults who suffered with the condition as a child. This approach can energise the staff who see the disease and issues a child may be facing from a fresh light.

Patient information aids

In a paediatric study, there are really two patients – the child and their parents. Information aids must be created with the needs of both in mind. To aid understanding and build a healthy relationship between site staff and patients, numerous tools could be utilised, including:

• Patient information DVD – an easily understandable method of receiving study-related information, especially for younger patients.
• Pop-up information booklets – strong visual representations of study procedures to take the anxiety out of treatment.
• Caregiver leaflets – to explain to parents what will happen to their child in a simple and comprehensive manner.
• Parental training – workshops/video for parents to help them learn the best way of answering questions from their child.
• Retention and support.

To maintain paediatric patient and parental engagement for the duration of the trial, consider the following methods:

• Coping skills leaflet – seeing a child unwell is heartbreaking for parents, so lessons in coping skills could reduce their stress and help them support their child more effectively.
• Parental support groups – allowing parents to talk with other parents of paediatric patients could provide a source of support and allow sharing of useful information.
• Child support groups – providing children of similar ages with the chance to talk about their hopes and fears may improve their coping skills.
• Patient rewards – while these will vary greatly by age, some useful materials could include fleece blankets to use during chemotherapy, CDs of fun music to keep them entertained through long hours in hospital, baseball hats to provide a cool way of covering hair loss, baggy sweatshirts so that they can feel comfortable and hide any weight gain caused by steroids, and puzzle books.
• Badges – to raise money for charity but that are attractive enough for patients to wear proudly. For example, the sponsor could make a donation to a paediatric cancer charity and have their company logo/name associated with helping these patients.

Adolescent studies

Compliance can be a particular challenge in adolescent patients, and filling in a patient diary, for example, may be an issue. Enhancing tools relevant to the age group such as use of the Internet rather than telephone questions via IVRS, and using e-mail for reminders will help compliance. Engaging the study site

Paediatric patients will have most of their contact in the hospital with paediatric nurses who will deal with their day-to-day care. Using these nurses in conjunction with doctors to explain the trials and help patients through difficult periods of studies is a key factor in retention. Trust is a big issue with children, so working on building relationships is another critical issue. It is important the study team work with the sites to understand how they can keep them motivated and provide the level of support they need and to make sure that the protocol is not placing demands on the patient that will prevent participation.

Approaches we can use to help the site

Well-researched, themed and tailored materials can be powerful tools for sites. They can help educate the patient while they are deciding whether or not to join the study, acting as patient support rather than recruitment items. A colourful and informative patient guide with clearly laid-out study details provides information on the study in a less daunting way than a 10- page informed consent document. This patient material complements the consent document and can be used by a site to “walk through” visits, as well as by a patient to discuss at home. A simple calendar with visit stickers is motivational for both the site and patients, as it allows the study coordinator to mark off planned visit dates and discuss planned holidays and commitment with the patient. Finally, placing all documents in a themed binder will motivate both the investigator and patient, as they are giving and receiving something special. In a recent study, investigators commented that the study calendar was their most useful motivational aid.

Enthusiastic CRAs pull recruitment together

By putting the patient first and investing time in planning, we can accelerate paediatric patient recruitment and retention through tailored, studyspecific, patient-focused approaches. To be successful, these need to be planned right from the start with a study identity that will resonate with patients and investigators. The use of tools, training and approaches to help the site connect with their patients leads to improved patient motivation and retention. The most successful approach is a holistic one, engaging the sponsor, project team, sites and patients with built in contingency plans, triggers and metrics to recognise and motivate all parties.

1. US Consensus Bureau, International Database

Dr. Janet Jones, Director, Global Patient Access and
Retention,

Dr. Janet Jones, Director, Global Patient Access and Retention, joined Kendle in 2000 and has overall responsibility for Kendle’s integrated patient recruitment and retention programmes; including analysing the specific drivers and challenges of conducting global clinical trials, developing study metrics, creating patient forecasts and defining and implementing patient recruitment strategies for study delivery. With more than 20 years experience in clinical research, she has gained a wealth of industry expertise as a CRA, lead CRA and project manager. Dr. Jones is widely-published molecular geneticist and patient recruitment and retention expert, with a doctorate in molecular biology.

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