Four Ways Biopharma Can Ease Patient Recruitment Difficulties For Clinical Trials
Recruiting enough suitable patients to participate in clinical trials is essential for developing new medicines. However, patient recruitment is frequently cited by trial Sponsors as one of the biggest challenges faced in running trials. Here we examine the impact that recruitment difficulties can have on clinical trials and four actions that can be taken with the help of statisticians to relieve these.
The impact of recruitment difficulties
Challenges with recruiting the required sample size within the planned timelines is a primary reason for study delays and ballooning development budgets. It is estimated that around 80% of clinical trials fail to recruit patients within the agreed timelines, with 37% of sites under-enrolling participants and 11% failing to enrol any. Clinical trial recruitment is estimated to take up to 30% of development timelines and cost around USD1.2 billion. Most clinical trials experience some delay due to recruitment. This often ranges from 1 to 6 months but in some cases, it can be considerably longer. It is estimated that each day of delay costs the pharmaceutical industry between USD 600,000 and 8 million.
From a statistical point of view, failure to recruit sufficient patient numbers impacts the integrity and validity of a clinical trial as the ability to meet the study objectives is dependent on achieving an adequate sample size. For example, if the sample size is too small, there is an increased risk of a type II error (i.e. it is more likely that no difference between treatments will be found when one does exist). This is the sponsor’s risk and can result in the project being abandoned unnecessarily. Most importantly, recruitment difficulties can create bottlenecks in clinical development by delaying the rate at which new treatments options can be approved and reach people with unmet clinical need.
The reasons behind poor recruitment
While there are many reasons for recruitment delays in clinical trials, a lack of awareness and the burden associated with being involved in a clinical trial are understood to be significant participant-related ones. Other issues that impact recruitment relate to funding, the research environment, the trial design, and trial/recruiter team with many of these preventable to some extent. Sponsors have sought to address patient burden in recent years, by embracing more patient-centric approaches to clinical trials. This has included harnessing innovative technologies that enable the decentralisation of trial activities so they can be performed more conveniently in a participant’s home or local healthcare facility. This has resulted in some trials being fully decentralised with others using a hybrid decentralised/site-based approach.
Trial design is an often-overlooked reason for poor recruitment. Many clinical trials protocols contain restrictive inclusion and exclusion criteria that make it extremely difficult to recruit patients that fulfil the criteria. In addition, protocols often contain impractical study procedures that are misaligned with existing care practices which mean it is difficult to find sites able to execute the study. They may also not consider the optimal number of patient observations required to have sufficient confidence in the data collected. There is often a threshold beyond which more data points make little difference to the overall confidence in the data. The use of real-world data, clinical experts, and patients themselves to assess the feasibility of the study is often not seen to be a critical part of the design process. In many cases, important sources of information are ignored in the pursuit of getting a study started and hitting key operational milestones. Increasing the likelihood of operational success before a trial starts through better trial design could ensure that recruitment targets are both realistic and necessary. This makes participation in a clinical trial more likely to result in a successful study outcome, a positive message for people considering joining future clinical trials. Here we outline simple strategies that Sponsors can employ to address recruitment challenges.
Four ways to alleviate recruitment issues before a trial starts
- Engage with statisticians earlier
Statisticians are often initially approached by Sponsors when it is time to calculate the sample size for a planned study. This usually occurs once most of the important decisions have already been made, many of which can impact recruitment targets. These include clinical endpoints, inclusion and exclusion criteria as well as timelines and budget. Engaging with statisticians so late in decision-making fails to harness the strategic insights they can provide at this key stage. Brought in earlier, they can help assess potential recruitment associated study risks upfront such as recruitment delays or being unable to fulfil the total sample size and offer strategies to mitigate for these that can be built into the study design. Statisticians can ensure that Sponsors are asking the right questions when planning a study and so ensure the best decisions are made given the specific recruitment constraints faced. Moreover, statisticians can rigorously evaluate the right patient population to recruit alongside the sample size required to answer the clinical question posed. This can help target recruitment efforts and resources into the right patient sample. They can also guide decisions in the face of recruitment difficulties once a trial has started.
- Invest more time in clinical trial design
Running a clinical trial involves hundreds of people, can cost on average around USD20 million and take years to complete. Its success is the gateway to the next stage of development, financing or even approval of a new breakthrough therapeutic. Yet despite this, little time and money is spent on optimising its design. This may be due in part to a pressure to stick with familiar designs in the rush to get trials started to meet timelines. However, with increasingly complex data to collect it is important that Sponsors are sure they have chosen the best design and analysis approach that considers potential recruitment risks before a study starts.
Statisticians have key expertise that can deliver the most value at the clinical trial design stage. Investing some time and money in working with them on evidence-based trial design at this pivotal stage can make the difference between a study’s success or failure. Statisticians can help derisk trials upfront through better design, ensuring studies are designed to collect the right data, in the right patients, in the right way. While this involves a little upfront cost, this can save considerable time and money once a trial has started and reduces its likelihood of failure.
- Consider unlocking information from historic and real-world data
While recruiting patients is a challenge for many studies, some research areas face more difficulties than others. Research into advanced therapies and orphan diseases requires extremely specific study criteria and it can often be difficult to find patients who meet these. Statisticians can offer viable work arounds for such studies. For example, they can search through historic data from a variety of sources including published clinical trials, disease registries and real-world data and evaluate the feasibility of using it in external or synthetic control arms for studies where there is likely to be constrained populations, such as in rare disease areas. Where there is sufficient suitable data for this to be feasible, they can then help to implement these according to the strict guidelines outlined by Regulators. While it is not always feasible to do this, where possible the use of external control arms can be instrumental in overcoming recruitment issues in research areas where there are small populations. Historic and real-world data can also provide invaluable evidence-based insights that can inform clinical trial design more widely and provide key information on specific patient populations.
- Explore the benefits of simulation
Despite record R&D spending, biopharma still experiences extremely high clinical trial failure rates. This places an unnecessarily heavy burden on people who choose to participate in these studies and sends out a negative message to those that may still be considering whether to join one. Therefore, there has never been a better time for Sponsors to take up technologies like simulation that support better clinical trial design and help boost study success. Safety conscious industries like car manufacturing and aviation routinely use simulation to test out their designs robustly in a virtual space before putting people into their prototypes and assessing them in the real world. In contrast, simulation is still not often used to evaluate the design of a clinical trial before patients are recruited onto it.
Simulation is an incredibly fast and cost-effective evidence-based method of optimising clinical trial design. It can be informed by the latest clinical information drawn from many data sources such as the literature, disease registries and real-world-data. It allows researchers to explore many what-if study design scenarios to identify the key drivers of study success. With simulation it is possible to examine risks in a virtual space, quantifying their impact on the likelihood of study success, and find ways to mitigate for these at the design stage. This includes the impact of recruitment in the form of patient sample sizes, populations and timelines on the ability to answer the clinical question posed.
Relieving patient recruitment issues in 2025
Difficulties with patient recruitment remains a serious challenge for Sponsors running clinical trials and biopharma must continue to understand the barriers and adopt more patient-centric approaches to overcome these. Nevertheless, simple options like engaging with statisticians earlier, investing more time in clinical trial design, unlocking historical data and utilising simulation offer four straightforward ways to address potential patient recruitment issues upfront. Statisticians can provide a more integrated approach to recruitment than providing a sample size estimate alone which can often pose more questions than it answers. By implementing these options in 2025, Sponsors can save time, money, and burden before the first patient has been enrolled into their clinical trial.