The sites selected for clinical trials are usually led by Principal Investigators (PIs) who are therapy area specialists and have managed previous clinical trials. However, due to this expertise they will have likely been chosen to conduct other respiratory clinical trials alongside yours. These other clinical trials are very likely to have similar criteria and may have overlapping patient pools. This raises the question of “how do you make your trials a high priority and maintain site motivation throughout?” Even the strongest or most experienced sites can run into challenges during clinical trials that can adversely affect their engagement and motivation for certain studies, and from our experience many sites encounter similar challenges and have related concerns. This blog will look at some site-focused challenges that can severely impact site effectiveness and motivation. For more information on patient-focused challenges that commonly occur during clinical trial patient recruitment, check out our previous blog post.
Preparing for Flu Season
With the flu season in the Northern Hemisphere usually occurring from October to May, we have a clear (but short) timeline for patient recruitment, so it is vital that sites are prepared and ready in time for the the start of the season to maximise the time available for patient recruitment. Any delays to starting patient recruitment can quickly snowball and cause significant delays further on. There are a few key site aspects that should be considered when preparing for flu studies.
Lack of time and full workloads are common issues encountered by clinical trial site teams when preparing for and conducting clinical trials. Site teams are usually extremely busy working with patients and regularly struggle to make time for trial related administrative activities. Ensuring your trial processes are efficient and that any available tools are easy to use can make each site’s workload a lot more bearable. The training for these tools should be concise, and FAQ documents or “cheat sheets” can be supplied in advance to preemptively answer any queries or give reminders. Site teams are usually also working on multiple clinical trials at once that have similar eligibility criteria and timelines while receiving multiple requests from different sponsors. Therefore, doing all you can to keep your sites happy and running smoothly can have a great effect on site performance. PIs and their teams can have a range of previous clinical trial experience levels; taking this into account when preparing sites and offering relevant training to teams can be helpful when getting sites onboarded. As part of our In-country 1:1 Site Support & Recruitment Coaching, our local Clinical Enrolment Managers (CEMs) regularly work with sites of all experience levels from site initiation visit (SIV) or activation to ensure sites have recruitment plans in place and have everything they need to start recruiting quickly. Site Specific Recruitment Plans (SSRPs) are a good way to set out each site’s plan for recruitment and also to get sites thinking about alternative options, important factors for the indication, and important factors for your clinical trial specifically. CEMs can manage this process and discuss important aspects in more detail to ensure sites consider a range of recruitment strategies to maximise patient recruitment. CEMs can also support rescue studies, discuss with sites what has been effective so far and what hasn’t, and then use this information to adapt a site’s recruitment plan to be more appropriate, efficient, and to boost patient recruitment. Sites can use their SSRP during the recruitment phase as a reference to keep on track with their original recruitment plan. With a short recruitment window, it is also key to hold sites to account so these SSRPs can be used later on to assess the site’s performance and compare their recruitment activities with their original SSRPs.
Planning out which recruitment materials will be effective in each country, which language translations are needed, what country or local regulatory approvals are needed, printing and shipping processes, and customs requirements are important factors to consider early in preparation. The recruitment materials process involves many steps that require review and approval, so getting it right the first time is hugely important to ensure that sites get the appropriate materials on time. Our in-house Branding & Materials Development Team are highly experienced with expediting these steps to ensure a streamlined development and approval process. They are able to advise on the correct materials for each country and which languages would be needed, develop these materials and have them translated, create submission packs for regulatory approvals, and manage the printing and shipping process on your behalf. Local CEMs can then follow up directly with sites to ensure they have received the materials, discuss how to use them effectively, and make sure they don’t end up left in the storage room.
A simple way to make sure your clinical trial is a high priority for sites is to listen and respond to them. Sites will likely have queries about certain aspects of a protocol or requests with related processes, and if your responses are delayed, or missed altogether, sites can quickly lose motivation as they don’t feel as though they are an important part of your trial, and your trial will slip down the site’s priority list. This may mean that potentially eligible patients are being assigned to other studies instead of yours. Having a clear escalation process and ensuring all concerns or queries are addressed quickly can ensure that sites remain motivated and engaged with your clinical trial and your trial management team. Our in-country CEMs regularly discover that sites have concerns that they have not shared with their CRAs, as CRAs usually do not have time to discuss recruitment aspects at length alongside all their other site responsibilities. It can take time for CEMs to understand these queries or concerns, then escalate them to the appropriate contact and ensure that sites get a response and/or resolution. If one site has a particular query or concern, it is highly likely that another site will have the same issue, so any resolutions should be distributed to all other sites to minimise repeat actions. Our CEMs regularly update each other on actions across countries to ensure all their sites have the information needed to recruit. Use of ongoing trial newsletters can be helpful to draw attention to these key updates, provide reminders where needed, and shout out success stories. Highlighting particular sites that are recruiting well can be great for overall motivation, but can also instil some competitive spirit to other sites to outperform their colleagues. We recommend that these newsletters be distributed at least quarterly and be relevant to all sites.
From our experience, another good way to discover site concerns and share clarifications is to get PIs and their teams together, and give them a forum to ask questions and discuss the clinical trial together. A great forum for this is during one of our Patient Recruitment Workshops led by our Patient Recruitment Teams either virtually, or in-person during Investigator Meetings. We highly recommend that each trial has at least one Patient Recruitment Workshop either at the beginning of a trial to aid preparation, or during recruitment to highlight any ongoing challenges, best practices, and boost patient recruitment. Patient Recruitment Workshops can be tailored to your trial specifics, the countries involved, and include information that is important to share with sites. Innovative Trials’ Patient Recruitment Teams will also run targeted interactive sessions during these workshops to discuss recruitment barriers and brainstorm mitigations, all while providing advice on a range of patient recruitment strategies that are tailored to the specific audience attending.
Innovative Trials recently conducted two sets of virtual Patient Recruitment Workshops for a Phase III cardiovascular clinical trial. The two sets of workshops were conducted 6 months apart to encompass newly activated sites due to staggered activation dates. A total of 359 site personnel from across 17 countries attended at least one of these workshops. Following the first workshops, a boost in recruitment activity was seen at sites that attended, with screening rates increasing by an average of 21% and randomization rates increasing by an average of 44%. After the second set of workshops, screening rates were maintained and randomization rates increased by an average of 12%. After the workshops, a ‘Key Learnings Document’ was shared with sites, summarising the key talking points and advice provided during the workshop for future reference. Feedback from sites mentioned that these were a great way to discuss challenges, see what other sites were experiencing, brainstorm new recruitment strategies, understand best practices, and boost motivation for the trial.
In-person workshops were also conducted at two regional Investigator Meetings for a global flu clinical trial at the start of the flu season to kick-start recruitment (NORAM and EMEA IMs). The workshop topics were developed using site data and flu surveillance data obtained during the previous flu season, and sites were consulted to gain information on key topics they wanted covered. During the workshops, a total of 132 site personnel from 71 sites across 10 countries were able to highlight and discuss common barriers they have experienced before, and work with Innovative Trials to brainstorm mitigation strategies for these. Specific recruitment goals were then set for each site to implement these mitigations and 87% of these goals were implemented.
Identifying Patients and Pre-Screening
It may sound obvious, but for a clinical trial to be successful, sites need eligible patients. However, identifying enough patients that fit the protocol’s eligibility criteria within the flu season timelines can be a lot more challenging than first expected by sites and sponsors. Making sure sites have effective recruitment strategies and a robust pre-screening process in place as well as to mitigating any problems that arise as quickly as possible, ideally preemptively, is critical to meet your recruitment targets on time.
Many sites rely on one or two main recruitment strategies to identify patients. Although these may be tried and tested by the sites, sometimes they are not being used to their fullest extent or sites may not have assessed other more effective strategies. A common recruitment strategy sites use is reviewing patients in their own database, usually by search codes such as ICD codes. A common limitation our CEMs discover with this strategy when supporting sites is that reviewing a database can seem like a mammoth task, especially at bigger sites with large databases. We recommend that the overall review is broken down into small achievable goals to make this a more manageable task. These goals may be around reviewing a certain number of patients a week, or a certain portion of the database within the next month. It can be helpful to assign these goals to certain team members who should do what they can to carve out time in their schedules for this and stick to the goals as close as possible. The goals should be reviewed regularly and adapted as needed to ensure they are achievable. Some sites quickly finish their database review, but have been found to be quite narrow with their search terms. It can be useful to consider what other codes or terms may be listed for potentially eligible patients and run another review to widen the patient pool. Another useful strategy is to focus on patients that are due to visit the site for any appointments soon. These can be contacted before their appointments to introduce the trial via recruitment materials, so they can attend their appointments already aware of the trial and ask any questions at the appointment.
A major factor that we have seen hamper recruitment efforts of sites on global clinical trials is a blanket approach to patient recruitment. It is important to have an overall patient recruitment strategy for a clinical trial, but it is essential to recognise that not all strategies will be appropriate in every country. Each country and site will have their own unique combination of characteristics that will influence how best to recruit patients, including but not limited to cultural, religious, socioeconomic and regulatory factors. Our in-country CEMs are very knowledgeable about their countries’ nuances and work with sites, in local language, to understand appropriate recruitment strategies, share advice and coaching on how to implement these strategies and provide on-going support to maximise the success of these strategies. For example, sites in the Republic of Korea do not commonly use external referrals as a strategy due to cultural reasons, so our Korean CEMs work with sites to put their efforts into more appropriate strategies such as schedule review and identifying patients at point of care. However, in Canada external referrals can be a very effective strategy to identify patients, so our Canadian CEMs discuss each site’s recruitment networks and work with sites to expand the networks and improve the number of referrals received from this network alongside other applicable recruitment strategies.
As discussed in the previous blog, raising patient awareness of the clinical trial is extremely important for fast moving trials. A good way to make the most of this patient awareness is via the use of trial websites and pre-screeners. Any recruitment materials that are used for your clinical trials ought to have QR codes or URLs directing possible patients to your clinical trial website. These websites should have a good overview of your trial, be written in language that is understandable to the general public, have translated features available, easy to access site contact information and will ideally also have a pre-screener. These pre-screening tools are effective to filter out people that are not eligible for the trial and to direct potentially eligible patients to contact their nearest participating trial site. Our team has developed and built many websites for trials that include pre-screening tools. They recommend that at completion of the pre-screeners the patient should be given the contact details of their nearest trial site as a minimum. A more efficient process would be to send the patient’s contact details directly to the site for them to follow up instead. Due to site staff’s busy schedules, they can find it difficult to contact all of these referrals in a timely manner. In order to reduce site burden, our Patient Navigators are experts at pre-screening patients. Referrals can be sent directly to the Patient Navigators, who will follow up with the patients, conduct a more in-depth pre-screening and gauge the patients interest to participate in your clinical trial. They will then transfer these patients directly to the trial sites to arrange the consenting process and screening, significantly reducing site burden as they will only receive referrals from likely eligible patients that are open to joining your clinical trial. Navigators recently supported a clinical trial, completing 5800 pre-screening calls, reducing site workload by 738 hours over 7 months – that’s over 30 hours a week back to site staff to focus on patient care and trial outcomes.
Patient-to-patient referrals, or parent-to-parent referrals for paediatric trials, can be a good way to reach a large range of people with minimal effort from the site. Making sure everybody that visits your site is aware of the trial in case they know of any friends or family members that may contract flu and are interested in your clinical trial can be very effective for wide-reaching contagious diseases like flu. The recruitment materials, trial website and pre-screener discussed above are vital to ensure that any referrals from this strategy have understandable information that is easily accessed with minimal burden on the referral.
Summary
As the saying goes, “proper preparation prevents poor performance”. It is vital that you prepare well and in time for sites to begin recruiting at the correct time relative to the flu season. And once this preparation is complete, you should be providing the sites with in-country extra support where necessary to maximise patient recruitment and ultimately reach your recruitment targets before the end of the flu season.
With all the effort to identify and enroll these patients onto your trial, they need to be retained to ensure your trial can be completed. Our next blog will focus on patient and site related retention challenges that are commonly experienced while conducting clinical trials.
Innovative Trials can provide a range of patient recruitment & retention services to expedite this preparation and ongoing site 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/
References
- Rangu and Maxwell, 2020, “Maximising Patient Recruitment”. https://repository.upenn.edu/entities/publication/28cfaa20-c5d7-4758-b8b1-299b09fcf575
- https://www.appliedclinicaltrialsonline.com/view/how-much-does-a-day-of-delay-in-a-clinical-trial-really-cost-