The clinical phase being a complex, expensive and lengthy process in drug development has several challenges in conducting and managing clinical trials that are either operational or medical/scientific in nature among them the major one is the recruitment and retention of patients.
Patient recruitment and retention despite more than two decades of focused attention and improvement efforts remains one of the largest challenges faced by clinical research enterprises today and is among the biggest causes of delay in drug development.
Additionally, patient recruitment now becomes increasingly difficult due to the rise in complexity of clinical trial designs, and stringent exclusion criteria which eliminate various populations resulting in disease heterogeneity while others exhibit trends towards targeted patient populations needed for fulfilling labelling requirements by regulatory agencies such as the FDA.
Successful completion of the drug development cycle within today’s competitive market needs timely enrolment of patients with the ability to maximize their retention.
Patient recruitment and retention pose various challenges that may be attributed to different factors such as study design, disease, patients, investigational sites and geographical areas where clinical trials are being carried out.
Potential Difficulties in Patient Recruitment and Retention
Protocol Obstacles
In recent years, the complexity of protocol development has increased in order to meet regulatory requirements and intended label claims. There has been a significant rise in several procedures performed during a study, the number of eligibility criteria, CRF pages and protocol amendments over the past few years.
The more complex the study protocol is, the harder it is to recruit or retain patients for research. Some studies will require patients to stay long hours at the hospital so that various tests can be done on them. A long wait like this can be very hard on some patients which may restrict their participation and retention in a study. Limitations on concomitant drugs and the need for a washout period also hinder patient recruitment as well as affect patient retention.
Placebo Use
Most of the study protocol designs involve the use of a placebo. When a placebo is one of the arms in a study, it becomes hard to convince patients and their family members to participate in the study, especially for psychological conditions and studies on pain management and other critical intervention conditions where real treatment is of essence to their conditions. The use of a placebo not only limits patient enrollment in a study but also presents severe difficulties concerning patient retention in a study.
Illness-Related Challenges
Patients’ illness conditions play a critical role in the process of patient recruitment and retention. In the case of oncology clinical trials, most of the patients are often fatigued with the disease and from the previous chemotherapy or radiotherapy which compels them to keep away from any clinical trial participation even if they are eligible for a study. The limited physical mobility and poor quality of life of patients due to disease prevent patients from participating in trials.
Patient Barriers
Diseases such as Alzheimer’s disease, Arthritis, Parkinson’s disease, and Prostate cancer are commonly seen in geriatric patients, and it is hard to enrol and retain these elderly patients in a clinical trial. The pediatric group poses altogether different and highly complex challenges, and therefore many clinical trials in this area, like pediatric diabetes trials, are open for recruitment for a long period and they fail to recruit patients on time and also retain them. Clinical trials are, always experiments, therefore in the minds of the patients and their family members, there is always a fear of side effects.
Informed Consent
If the Informed Consent Form (ICF) is not properly designed and provided, the study-related information to patients and their family members in simple, understandable language, then a lack of interest towards Clinical Trials arises. Also, getting a proper translation of the ICF is also important so it gives correct information as to the original ICF, and the translation should give the correct meaning in context to culture.
The process of ICF is even more difficult to conduct in a psychiatric trial, where sites have to deal with patients affected by insight, awareness, mood as well as cognitive abilities, thus influencing the consent capacity of the patients, which can limit patient recruitment on such studies.
Geographic Location
Country selection is very important in any clinical trial. Apart from sponsor requirements for country selection, one has to understand the culture, epidemiology, prevalence and incidence of disease patterns, country regulatory requirements, ethical needs, standard of care, clinical practice and experience of PI/sites in handling the specific clinical trial under question. The country should offer an adequate number of potential patients in that indication to complete the recruitment on time. In the case of a few countries, there are good physician-patient bonds, and the patients perceive the physicians to be very vital in the healthcare arena.
In such countries, patients can join a clinical trial as per the physician’s recommendation. There are a few countries where a family structural role is significant, affecting patients’ participation in a trial. Again, proper selection of the investigator based on speciality is also very important to have a good pool of patients at sites.
Site Staff
Poorly trained site staff taking control of study subjects can adversely affect study participation. The site staff should be well-trained or sensitized approach-wise in handling patients- that is, during the consent process as well as throughout the duration of the study. They should be able to respond to the queries of the patients and their family members very effectively and need to provide the confidence to facilitate patient enrolment. The lack of study‑related knowledge would hinder patient recruitment and retention.
Also, site staff need to take care of timely reimbursement of patients and their family members with regard to travel and sustenance to keep on encouraging the patients in the study. This is instrumental in optimizing the retention of patients.
Proposed Solutions For Subject Recruitment
For progressive, on-time patient recruitment in a trial, a combination of the following methods can be adopted:
GCP recommends that before initiating a trial, the investigator/institution should have approval from the Institutional Review Board (IRB) / Institutional Ethics Committee (IEC) for the subject recruitment procedures such as advertisement and all other written material that is to be distributed to research subjects.
Advertisement
Mass media like newspapers, radio, television and websites can be used to advertise for subject recruitment. Abiogenesis can design special user-friendly websites to ensure patients get information on the clinical research study for the site.
Broadcasting: Using Social Media Websites
It could also include social networking channels such as Facebook, Twitter, MySpace, YouTube, and patient websites to identify or locate relevant subjects. This technique would be helpful in capturing information in near real-time as and when it is updated by the patient.
Industry-Wide Health Databases – Claims, Hospital Discharge etc.
Healthcare Cost and Utilization Project (HCUP) Databases contain information on in-patient stays, emergency department visits and ambulatory care.
HCUP databases can be utilized for patient enrolment as discussed below:
- Derivation of the list of hospitals that have treated a specific set of patients.
- Thus, the information about the doctors and the site can be extracted for a particular therapeutic area.
- This will be mapped with the trial information i.e. keywords derived from study eligibility criteria.
- By utilizing these trial registries, the data is analyzed and extrapolated to draw the history as well as the current experiences of the investigator and site from the point of view of patient enrollment, trial completion status etc.
Use of Mapped Electronic Medical Records (EMR) with Claims Data
- Claims consist of data related to medical services, i.e., in-patients, out-patients, information about pharmacy, etc. provided to patients. The information is not in detail and has a high level of ICD coding, with missing severity about the condition.
- EMR data is exhaustive with laboratory results, vitals, clinical data, etc., captured at the point of care.
- The above two can be used to the sponsor’s advantage in improving subject recruitment by mapping claim data to EMR and thereby allowing the thoughtful review of patients within the trial eligibility.
- Accordingly, the patients and sites can be contacted for study enrollment and hence, the process can expedite the patient recruitment rate.
Detaining Information From Clinical Trial Registries
Based on information available at various clinical trials registries like but not limited to clinicaltrials.gov, www.clinicaltrialsregister.eu. we shall develop an interactive interface in line with the keywords. The information derived shall be mapped with the trial keywords to help pick the sites with the best historical performance across the globe.
Patient retention strategies:
- Planning visits with sites for initial / follow‐up visits and offering flexible/convenient appointment times
- Spending extra time with patients to understand their concerns and address them effectively
- Summary of laboratory results to patients to demonstrate progress
- Appointment reminder services
- Travel assistance for patients/family members/caregivers, and patient compensation service
- Identifying the warning signals for potential drop‐outs and working closely with the subjects to support them to continue on the study
- Lost to follow‐up recovery
- Better communication strategies and management using proper resources, credible technology, and strategy of technology can retain the functional number of clinical trials and their participants, in a timely manner and at the scheduled duration
Conclusion
Patient recruitment and retention are challenges which the industry has faced over many years, and they warrant a systemic, practical approach, especially in some complex and ‘difficult to recruit’ kinds of studies, in order to ensure the successful completion of the clinical development phase. Problems in patient recruitment and retention should be fully anticipated at the study planning and protocol development stage. Accordingly, proactive planning can be done to ensure patient recruitment on time and to maximize retention. The success lies in effectively addressing study challenges and hurdles in patient recruitment and retention with country- and site-specific, innovative, practical and result-oriented strategies within the framework of regulations to provide timely and cost‐effective results.
