A clinical trial cannot answer its research question without participants.
Yet patient recruitment continues to be one of the
most persistent operational challenges in clinical research. A scientifically
rigorous protocol, experienced investigators, adequate funding and
sophisticated technology cannot compensate for a study that cannot enroll and
retain the population it was designed to investigate.
The consequences extend beyond delayed timelines.
Recruitment difficulties can increase study costs, require additional sites or
countries, reduce statistical power and, in some cases, contribute to premature
trial discontinuation. Research examining discontinued randomized trials has
identified poor recruitment as the most frequently reported reason for
discontinuation. [1]
But recruitment is only half of the challenge.
A participant who consents but subsequently withdraws
or is lost to follow-up may also affect study completeness and
interpretability.
The more useful question for modern clinical research
is therefore not simply:
“How do we recruit more patients?”
It is:
“How do we design and deliver clinical trials that
eligible patients can understand, access, participate in and remain engaged
with?”
That shift—from recruitment as a numerical target to participation as a patient journey—is fundamental to more effective clinical development.
Recruitment Starts Long Before the First Patient Is
Screened
Recruitment problems are often treated as site-level
problems that emerge after activation.
By then, some of their underlying causes may already
be embedded in the protocol.
Consider a study with:
- Highly restrictive eligibility criteria
- Numerous hospital visits
- Long visit durations
- Frequent blood sampling
- Complex diagnostic procedures
- Narrow visit windows
- Extensive questionnaires
- Long travel requirements
- Limited flexibility for working participants or
caregivers
Every requirement may have a scientific rationale.
Collectively, however, they can create a study that is
extremely difficult for patients-and sites-to deliver.
Recruitment strategy should therefore begin during protocol development and feasibility, rather than after sites begin missing enrolment targets.
The Difference Between Available and Recruitable
Patients
One of the most common feasibility mistakes is
assuming that the number of patients with a disease corresponds to the number
available for a clinical trial.
It rarely does.
The actual recruitment funnel may look more like this:
Patients
with the condition
↓
Patients
attending participating institutions
↓
Patients
meeting key clinical characteristics
↓
Patients
satisfying all inclusion criteria
↓
Patients
without exclusion criteria
↓
Patients
not committed to competing studies
↓
Patients
considered appropriate for screening
↓
Patients
willing to participate
↓
Patients
who successfully complete screening
↓
Patients
actually enrolled
A hospital may therefore treat hundreds of patients
with an indication while only a fraction are realistically recruitable.
This is why robust feasibility must examine the assumptions underlying enrolment projections—not simply collect an estimated number from each investigator.
Why Do Patients Decline Clinical Trial Participation?
There is rarely a single reason.
Participation decisions can be influenced by the
disease, treatment options, study design, healthcare system, geography and
individual circumstances.
Common barriers may include:
Limited awareness
Patients may not know that an appropriate clinical
trial exists. Their treating healthcare professionals may also be unaware of
available studies.
Travel and accessibility
Frequent visits to a distant research centre can make
participation impractical.
Time commitment
Study visits can conflict with employment, education,
childcare or other responsibilities.
Concerns about the investigational intervention
Patients may be uncertain about potential adverse
effects, randomization or receiving a comparator/placebo where applicable.
Complex information
Long or highly technical participant information
documents can make an already difficult healthcare decision even more
challenging.
Financial and logistical burden
Transportation, accommodation, meals and time away
from work may influence participation depending on the study and local
arrangements.
Cultural and language barriers
Information that is technically translated but not
culturally understandable may still create barriers to meaningful
participation.
These factors remind us that eligibility does not automatically translate into accessibility or willingness to participate.
Informed Consent Is a Process, Not a Recruitment Tool
One of the most important distinctions in clinical
research is between recruitment and informed consent.
Recruitment identifies and approaches potentially
eligible participants.
Informed consent enables individuals to make a
voluntary, informed decision about whether participation is right for them.
The two should never be conflated.
The 2024 revision of the Declaration of Helsinki
reinforces the importance of free and informed consent and of providing
potential participants with understandable information regarding the aims,
methods, anticipated benefits, potential risks and other relevant aspects of
research. [2]
Similarly, ICH E6(R3) places participant rights,
safety and well-being at the centre of Good Clinical Practice. [3]
A successful recruitment strategy is therefore not one
that persuades the greatest number of people to enroll.
It is one that enables appropriate participants to
make genuinely informed choices.
Why Patient Retention Matters
Enrollment is not the end of the participant journey.
Depending on the protocol, participants may remain in
a study for weeks, months or years.
During that period, they may be expected to:
- Attend repeated study visits
- Complete questionnaires
- Provide blood or other biological samples
- Undergo imaging or diagnostic procedures
- Take investigational treatment according to
schedule
- Maintain diaries
- Use digital devices
- Report adverse events
- Attend long-term follow-up visits
Each additional requirement creates participant
burden.
When the cumulative burden becomes excessive, missed
visits, protocol deviations and withdrawal become more likely.
Retention should therefore be considered during trial design, not only when dropout rates begin increasing.
Participant Burden Is Also a Scientific Issue
Patient-centricity is sometimes described as an
ethical or engagement objective.
It is both of those things—but it can also affect
scientific quality.
Consider a protocol requiring frequent clinic visits.
If those requirements disproportionately exclude
people who:
- Live far from major research centres
- Have mobility limitations
- Cannot frequently take time away from work
- Have significant caregiving responsibilities
the recruited population may differ systematically
from the broader population affected by the disease.
Similarly, if burdensome procedures contribute to
differential dropout, missing data may affect interpretation of study outcomes.
Designing studies around realistic participant circumstances can therefore support both patient experience and evidence quality.
Diversity and Representation Matter
Clinical research should generate evidence relevant to
the populations expected to use an intervention.
Historically, some populations have been
underrepresented in clinical research. Regulators and research organizations
have increasingly emphasized improving representation in clinical development.
However, diversity cannot be achieved simply by
stating a recruitment target.
Sponsors and CROs need to understand barriers
affecting different communities, which may include:
- Geographic access
- Language
- Socioeconomic circumstances
- Trust in research
- Referral pathways
- Eligibility criteria
- Healthcare access
- Awareness of clinical trials
Site selection and recruitment strategy therefore need
to consider where relevant patient populations actually receive care.
A prestigious academic centre may be scientifically attractive, but a broader site network may sometimes be necessary to improve access and representation.
Sites and CRCs Are Central to Recruitment Success
The Clinical Research Coordinator (CRC) often becomes
one of the most important points of contact in a participant's study
experience.
CRCs may coordinate:
- Screening
- Study visits
- Participant communication
- Scheduling
- Study procedures
- Documentation
- Follow-up
- Investigator communication
Strong CRC engagement can improve operational
continuity and participant experience.
This is one reason why site feasibility should
evaluate not only the Principal Investigator but the entire site research team.
Does the site have adequate coordinator capacity?
How many competing studies are CRCs managing?
How quickly can the team respond to participants?
Can visits be scheduled flexibly?
Is there adequate backup coverage?
These operational details can have a meaningful impact on recruitment and retention.
What Can Improve Recruitment?
There is no universal recruitment strategy.
Approaches should be tailored to the disease,
protocol, population and geography.
However, several principles can improve planning.
1. Use evidence-based feasibility
Enrolment projections should be challenged against
actual patient pathways, historical performance and relevant data wherever
available.
2. Engage sites early
Investigators and CRCs can identify protocol barriers
that may not be obvious during central protocol development.
3. Consider patients during protocol design
Patient input can help identify burdensome procedures,
unrealistic schedules and communication challenges before the protocol is
finalized.
4. Develop realistic enrolment forecasts
Aggressive recruitment assumptions may make a
development plan appear attractive initially but can create significant
downstream delays.
5. Understand referral pathways
Not every eligible patient will already be treated at
an investigative site. Referral networks may therefore be critical.
6. Review competing studies
Competition should be assessed during feasibility and
monitored as the recruitment environment changes.
7. Communicate clearly
Participant-facing materials should be understandable, accurate and appropriate for the intended population.
What Can Improve Retention?
Retention strategies should focus on removing
avoidable barriers while maintaining scientific integrity.
Depending on the protocol and applicable requirements,
this may include:
- Flexible visit scheduling
- Appropriate travel support
- Clear visit reminders
- Reduced unnecessary procedures
- Participant-friendly study materials
- Remote assessments where scientifically and
operationally appropriate
- ePRO/eCOA solutions
- Home health services where permitted
- Consistent communication
- Long-term engagement strategies
Technology can help—but technology itself is not
patient-centricity.
An app that participants find difficult to use simply
replaces one burden with another.
Digital solutions should therefore be selected based on fitness for purpose, accessibility and the needs of the study population.
Decentralized and Hybrid Trials: Part of the Solution?
Decentralized clinical trial approaches have created
opportunities to move certain trial activities closer to participants.
Depending on the study, these approaches may include:
Telemedicine | Remote monitoring | eConsent | ePRO |
Wearable devices | Home nursing | Direct-to-patient services
The FDA has issued guidance addressing decentralized
elements in clinical trials, reflecting their growing role in clinical
development. [4]
These approaches may reduce travel and expand access
for some participants.
However, decentralization is not automatically
appropriate for every protocol.
Complex interventions, intensive safety monitoring,
specialized procedures or certain patient populations may still require
substantial site-based care.
The goal should therefore not be to make every trial
decentralized.
It should be to determine:
Which trial activities genuinely need to happen at the research site—and which could safely and reliably happen closer to the patient?
Recruitment Is a Shared Responsibility
When enrollment is slow, it can be tempting to label
it simply as a “site performance problem.”
Sometimes it is.
But recruitment is influenced by decisions made across
the entire study:
Protocol Design → Country Strategy → Site Selection →
Feasibility → Regulatory Timelines → Site Activation → Patient Identification →
Communication → Participant Experience
Sponsors, CROs and sites therefore share
responsibility for creating realistic recruitment strategies.
A site cannot recruit patients who do not exist.
A CRO cannot compensate indefinitely for an
impractical protocol.
And a sponsor cannot solve recruitment simply by
adding more sites if the underlying feasibility assumptions are incorrect.
Successful recruitment requires alignment across the system.
Recruitment Metrics Need Context
Enrollment numbers remain important, but they should
not be interpreted alone.
Useful operational metrics may include:
- Screening rate
- Screen-failure rate
- Enrollment rate
- Recruitment rate per active site
- Time from activation to first participant
- Participant withdrawal rate
- Lost-to-follow-up rate
- Reasons for screen failure
- Reasons for withdrawal
A site enrolling fewer participants than forecast may
have an unusually high prevalence of a protocol-defined exclusion criterion.
Another site may enrol rapidly but experience
significant subsequent withdrawals.
Understanding why performance differs allows study teams to respond intelligently rather than simply applying pressure to sites.
From Patient Recruitment to Patient Partnership
Perhaps the most important evolution is conceptual.
Clinical research traditionally spoke about recruiting
subjects.
Modern clinical development increasingly recognizes
the value of engaging participants and patients as partners.
That can begin before recruitment through patient
involvement in:
- Protocol development
- Endpoint selection
- Visit scheduling
- Participant materials
- Technology selection
- Burden assessment
- Dissemination of study results
Patients understand aspects of living with a disease
that cannot always be captured through literature reviews or epidemiological
datasets.
Incorporating that perspective can make clinical research both more relevant and more feasible.
The Agile Clinical Trendz Perspective
At Agile Clinical Trendz, we believe successful
recruitment begins before the first site is activated.
It begins with understanding:
the disease, the protocol, the patient pathway, the
site environment and the practical realities of participation.
Effective recruitment and retention therefore require
integration across protocol feasibility, country and site selection, clinical
operations, site management, CRAs, CRCs, regulatory teams, data functions and
patient-facing activities.
The objective should never be enrollment for
enrollment's sake.
The objective is to identify appropriate participants,
support informed decision-making, reduce avoidable participation barriers and
retain participants while maintaining scientific and ethical standards.
Because ultimately, clinical trials do not succeed
simply because they reach an enrollment target.
They succeed when patients can meaningfully participate and the resulting evidence is reliable enough to advance healthcare.
References
- Kasenda B, von Elm E, You J, et al. Prevalence,
characteristics, and publication of discontinued randomized trials. JAMA.
2014;311(10):1045–1051. doi:10.1001/jama.2014.1361.
- World Medical Association. World Medical
Association Declaration of Helsinki: Ethical Principles for Medical
Research Involving Human Participants. JAMA. 2025;333(1):71–74.
doi:10.1001/jama.2024.21972.
- International Council for Harmonisation of
Technical Requirements for Pharmaceuticals for Human Use. ICH
Harmonised Guideline E6(R3): Guideline for Good Clinical Practice.
Final guideline. 2025.
- U.S. Food and Drug Administration. Conducting
Clinical Trials With Decentralized Elements: Guidance for Industry,
Investigators, and Other Interested Parties. FDA; 2024.
- Huang GD, Bull J, Johnston McKee K, et al.
Clinical trials recruitment planning: A proposed framework from the
Clinical Trials Transformation Initiative. Contemp Clin Trials.
2018;66:74–79. doi:10.1016/j.cct.2018.01.003.
- Treweek S, Pitkethly M, Cook J, et al. Strategies
to improve recruitment to randomised trials. Cochrane Database Syst Rev.
2018;2(2):MR000013. doi:10.1002/14651858.MR000013.pub6.
- National Academies of Sciences, Engineering, and Medicine. Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups. Washington, DC: National Academies Press; 2022.