Patient retention is a hugely important factor for clinical trials and is just as vital as patient recruitment. A high retention rate of patients is critical for the validity and credibility of your clinical trial, and you don’t want your hard work to overcome recruitment challenges and enrol patients to go to waste due to underestimating patient retention. High withdrawal rates mean more than two-thirds of trials fail to meet their goals (Fogel, 2020), leading to extended recruitment periods, potential increased costs to open additional sites, and ultimately delayed, over-budget trials. A 2023 study calculated that the daily cost of delayed trials can reach approximately $500,000 in lost drug sales and $40,000 in direct clinical trial costs per day of delay (appliedclinicaltrialsonline.com), so having to extend or reopen recruitment will have significant impacts on costs and revenue. Some companies factor in a patient withdrawal rate as high as 30% when planning a clinical trial, which may seem high but withdrawals can even exceed 30% (National Academy of Sciences, 2010) if appropriate patient retention strategies are not implemented early and sites are not supported effectively. Waiting until the recruitment phase finishes to implement patient retention strategies means that you are likely already too late. Patient retention should be considered as early as possible and discussed with sites prior to recruiting their first patient to ensure a minimal amount of patients withdraw throughout the trial.

This blog will discuss some important aspects to consider to maximise patient retention on your clinical trial. For more information on patient recruitment considerations, check out our previous blogs about patient and site considerations.

Patient-Centric Retention

During the course of a clinical trial, a patient can discontinue at any time. This may be due to medical reasons or side effects that cannot be prevented. However, many patients withdraw for potentially avoidable reasons. The main reasons for patient withdrawals can usually be sorted into three main categories: inconvenience, lack of appreciation, and loss of interest.

  • Inconvenience – Trials rely on patients making changes to their usual schedule and taking on additional burden for study visits and other study related activities. This can include travelling to visits, taking time off work/school for visits, and patients having to include trial activities in their lives. Patient inconvenience is heightened by trials that have a high number of visits, high frequency of visits, or intensive visits.
  • Lack of appreciation – Taking part in a clinical trial can be a burdensome and potentially scary process for a patient. Participants who don’t feel valued during a trial may believe they aren’t making a meaningful contribution or receiving any appreciation for their time and effort. This can be particularly common in trials with high patient numbers per site.
  • Loss of interest – Patients can quickly lose interest in a trial if the trial is long, if there are lots of visits, or if they don’t see the benefits of participating. With loss of interest, patients are more likely to forget or just not attend visits or complete study activities, which could lead to discontinuation.

To combat these retention risks, retention strategies should be tailored to the overall patient population but also to each individual patient. To do this, you need to consider a patient’s experience when taking part in your trial, from when they are first introduced to the trial all the way through to the final follow-up visit, and not just in terms of what they need to do to adhere to participation guidelines. 

Early in a patient’s clinical trial journey, it is important that patients are educated about your trial but also about clinical research in general to give context, ensuring that any information given to patients (and/or caregivers if applicable) is clear and there are opportunities for them to ask questions. (Please refer to our previous blogs for more information on developing and using effective recruitment materials and tools). Patients are likely to have a lot of questions, so providing site contact details so they can ask any questions following visits is very helpful. This is most effective if the patient has already met that particular site member during screening as they will have already developed a relationship. Patient education can help overcome some initial barriers such as misunderstanding of the purpose of the clinical trial, negative views on clinical research, and apprehension on certain trial procedures, such as injections or imaging scans. This is vital for indications such as the flu or other respiratory diseases that have a lot of existing remedies on the market, or for vaccine trials as there is a wide range of views on clinical trials since the Covid-19 pandemic.

For trial visits, it is worth considering the whole process from a patient’s point of view to ensure they are as comfortable as possible and any inconveniences are to a minimum. Providing reminders prior to visits with key information such as timings and procedures, along with clear instructions on how to get to the study site can help patients plan their day. Use of materials that show the whole trial process and highlight which procedures are at each visit can boost patient understanding of what they will be going through. Some patients may have financial challenges and be unable to pay for transport up front, so any available travel vendors or tools should be used to make sure patients have transport options available to attend their visits and get home afterwards. If these aren’t available, an efficient reimbursement process should be in place so patients are not out of pocket for long. During screening, any additional accommodations that may be required should be discussed with patients, including but not limited to obtaining information on any disabilities of those attending visits that may be relevant, sharing information on step-free access to the site, identifying the need for translators or interpreters if there is a language barrier, or anything else that impacts a patient or their caregivers attending the visits. 

Next, consider a patient’s experience when they are at the site. Making sure that they are greeted by a member of the site team can help set their minds at ease for what could be a stressful time for them. Each patient and any caregivers should be introduced to the site team so they are able to recognise the team and build a relationship with them. A visit day is likely to involve many tests and patients can be at the site for a number of hours, so making them comfortable during this time is vital. Any adults that attend will probably need to take time out of work and any children may need to take time out of school to attend visits, so providing a quiet area for them, with amenities such as power sockets and access to Wi-Fi, to allow them to work or study may be appreciated. Having a stock of toys and games for any children that accompany patients to visits can keep them occupied and will reduce patient stress during the visit. On top of these, specific flu symptom considerations should not be overlooked: Easy access to refreshments is a must for keeping hydrated, as well as making the waiting room as comfortable as possible with comfy seating for aches, climate control for fevers, and tissues for runny noses. Our in-country Clinical Enrolment Managers (CEMs) work closely with sites to understand their patient population, discuss common retention risk factors and how to mitigate them, how best to utilise available tools, and how to adapt processes to accommodate an individual patient’s needs.

Finally, consider what happens when a visit is completed. Patients/caregivers should be given clear instructions on when the next visit is and what may be needed in the meantime (e.g. eDiaries or reimbursement processes). A follow-up email or call can also be effective to ensure a patient feels like a key part of the team and their contribution to the study is valued. Our Patient Navigators are experienced at providing patient contacts, such as reminders, follow-ups, and being the primary point of contact for patient queries. The Navigators regularly act as a kind ear for patients to discuss their trial apprehensions, ensuring patients feel listened to, reassured, valued, and hopefully retained.

The use of retention items as a small token of appreciation can work well to keep patients motivated and feel appreciated during a trial. These items should be themed towards the relevant indication and will ideally be branded with the study logo to raise awareness. For flu trials, these items may include: blankets and water bottles to combat fever symptoms; stress balls for anxious site visits; or ice packs for headaches or body aches. Our in-house Branding & Materials Development Team regularly develop, source, and ship retention items to sites around the globe; they can work with your trial teams to identify appropriate materials for your trial and patient population. Retention items are particularly effective for paediatric trials, as giving an item at each visit or study milestone can allow patients to look forward to the next visit and item rather than be apprehensive. To support paediatric patients, we have partnered with the non-profit Oliver Patch Project to create The Retention Patch Program, aiming to boost participant retention in paediatric studies through the power of patches. This global program offers love and support to every child, teenager or family engaged in a clinical trial, fostering a sense of community for all clinical trial participants regardless of condition and therapy area. 

Site-Centric Retention

Many retention strategies will focus on patient-centric aspects, but you must not forget that your sites also need to be supported in order to conduct those targeted retention activities effectively. Successful retention starts with recruiting patients that are engaged and seem reliable. During the recruitment phase, sites should not neglect retention activities as this may have a negative impact on early retention rates, potentially resulting in additional patients being required to meet trial targets. Similar to patient-centric strategies, it is important to provide support to sites to minimise inconvenience, lack of appreciation, and loss of interest.

Site teams are extremely busy so retention activities can sometimes be missed, while CRAs have a multitude of trial related topics to monitor so may not be able to spend time discussing specific retention risks in detail. With fast-moving diseases like flu, trials commonly include a number of patient visits in quick succession that have multiple procedures and tests involved. These will increase the level of inconvenience for both patients and sites, with any issues that arise being time-sensitive and needing urgent attention. Sponsors should endeavour to respond to these actions quickly and provide clear responses, ensuring that sites know they are appreciated and a vital part of the clinical trial. Establishing a clear escalation process, including backup contacts in case of unavailability, is a good way to answer queries quickly and reduce the possibility of queries being missed. 

It is critical that sites are well organised in order to manage their patients and keep on top of administrative activities for each visit. This can be supported by providing visit procedure reminders or FAQ-like materials for sites to reference during each visit as well as reviewing site procedures and providing best practice advice where required. Good organisation is particularly relevant for trials that have a high number of patients per site as sites can quickly get overwhelmed, potentially leading to significant problems. It is worth noting that sites are likely conducting multiple clinical trials at the same time with similar timelines and may be receiving a large amount of communications or requests from different sponsors. Therefore, making your messaging to sites unambiguous and direct will help raise your actions up a site’s priority list. Our CEMs have extensive experience providing Retention Support to sites to make sure they are organised, are able to manage their patients effectively, and follow-up on pending escalations where required. CEMs develop an understanding of each site’s previous experience with retention and adapt their support accordingly. Feedback on previous trials shows that sites appreciate having a specific contact to discuss these aspects in detail and talk about any challenges they encounter. Retention Plans can be useful to understand each site’s planned retention strategies and get sites thinking about potential risk factors that may arise during the trial. These plans can then be referred back to during the trial to keep the site’s retention activities on track. CEMs can facilitate the development of these Retention Plans while providing advice on retention best practice and highlighting key risk factors. You may also be using online tools to track visits and provide these reminders. These can be extremely useful but please bear in mind that the site teams may be using multiple platforms across different trials, so any tools provided should be user friendly and any useful guides should be made available. Our Patient Navigators can become experts on your travel or reimbursement platforms, as part of on-going patient support, to act as the main point of contact for patient queries, reducing site burden and allowing them to focus on other trial activities instead. 

Over time, it is very common for sites to become demotivated with a trial, especially if they are struggling with keeping on top of administrative tasks, with patient numbers, or if they have had a number of withdrawals. If this happens, it is vital to boost motivation for your trial. An effective way of doing this is via Retention Workshops. Similar to the Recruitment Workshops mentioned in the previous patient recruitment blogs, these Innovative Trials-led Retention Workshops will gather principal investigators (PIs) and other site staff across different sites and countries to discuss retention in more detail, introduce or recap available vendors/tools, give sites an open forum to ask questions, clarify certain protocol points or visit procedures, and share their previous experiences with each other. From a sponsor’s point of view, these workshops allow you to identify potential risks, assess how widespread they are, and help develop widespread or targeted retention support for specific countries or sites. The Retention Workshops could be conducted early in a trial, to highlight key retention risks, share best practice and prepare sites for retention activities. However, they are also effective once sites have patients enrolled and have experienced potential retention challenges as booster Retention Workshops. The topics of these workshops also address common retention risks, but would focus specifically on current retention challenges encountered by sites, sharing best practices and experiences between sites, and suggesting mitigations where possible. The timing of these workshops needs to be considered carefully as the flu season encompasses many religious and cultural holidays as well as country-specific holidays that will impact the availability of your sites. Depending on the countries involved, booster workshops are effective in January or after any relevant major religious/cultural holidays to re-engage sites with your trial. 

Booster Retention Workshops were conducted by Innovative Trials earlier this year for a large global Phase III study, with 159 site personnel from 72 sites attending the workshops. The aim of the workshops was to get sites thinking about patient motivations and experiences in the clinical trial, and share appropriate retention strategies, ultimately re-engaging and re-motivating the sites. 85% of attendees said that these Retention Workshops were useful, and 92% of attendees said that they would be interested in participating in a similar workshop in the future. 

Summary

The importance of patient retention is commonly underestimated, with many sponsors implementing retention strategies too late for sites to retain early patients or developing strategies that are not targeted to the patient pool or adapted across different countries/sites, usually resulting in trials with delayed timelines that are over-budget. Any retention strategies developed should focus on reducing inconvenience, lack of appreciation, and loss of interest as patients are less likely to withdraw from trials if they feel valued and well supported. These strategies should take patient experience into account as well as any other considerations that may be needed for the patient population to make your trial a valid option for as many patients as possible, noting that these strategies may vary across countries due to unique nuances across different countries and sites. Many retention strategies will be patient-centric, but sites must not be neglected. Making sure that sites are kept engaged with your trial, kept motivated to complete trial tasks, and offered the support needed to stop them becoming overwhelmed can be vital in ensuring your trial runs smoothly. Your clinical trial is more likely to be a high priority for sites if they feel appreciated and a key part of the trial. 

Innovative Trials can provide a range of patient recruitment & retention services to expedite this preparation and provide ongoing site and patient support. For more information on how this can benefit your clinical trial, we are offering a free 30-minute strategy call with our CEO Kate Shaw to ensure your influenza studies stand out from the competition: 

https://itrials-bd.youcanbook.me/ 

 

 

 

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