Recruitment Enhancement for Trials Aimed at Individuals At-Risk for Rheumatoid Arthritis

Investigators identified both facilitators and barriers for trial participation in patients at risk for rheumatoid arthritis (RA) in order to enhance inclusion in trials designed to prevent RA, according to a study published in BMJ Journals.¹ Results emphasize education about RA, trial medication, debunking misconceptions, listening to patients’ concerns, addressing personal risk, limiting study burden, and encouraging physicians to mention trial participation and trial aim.

“Given the tendency to treat RA very early, sometimes even before definitive RA diagnosis, the importance of prevention trials will increase,” stated investigators. “Therefore, it is crucial to better understand at-risk individuals’ motives in order to improve recruitment into preventive trials.”

Unfortunately, preventative trial participation for at-risk patients have historically severe recruitment difficulties, sometimes needing up to 5 years to achieve their aims. The at-risk phase is defined as the period before clinical arthritis onset, during disease development, in which symptoms and biomarkers are present.

Eligible individuals were at risk for developing RA and had previously been asked to participate in preventative trials. Patients aged ≥18 years with anticitrullinated protein antibodies (ACPAs) >3× the normal limit or both ACPA and rheumatoid factor (RF), and no medical diagnosis of arthritis were considered.

During the study, which took place between November 2015 and January 2019, 33 individuals accepted an invitation to participate in a focus group discussion (FGD). However, after 3 focus groups of 18 individuals, investigators had enough data to stop inclusion. Participants were able to choose between 2 multicenter, randomized, double-blind, placebo-controlled clinical prevention trials: The STAtins to Prevent Rheumatoid Arthritis (STAPRA) trialand the Arthritis Prevention In the Pre-clinical Phase of RA with abatacept (APIPPRA) trial. The STARPA group received atorvastatin 40 mg daily for 3 years and the APIPPRA cohort received subcutaneous abatacept 125 mg weekly for 1 year.

Of the 18 participants, 9 took part in a randomized trial (8 for STARPA, 1 for APIPPRA) and 9 had declined participation. The mean age was 59 years, and 56% were women. FGDs were then conducted in order to identify facilitators and barriers for trial participation using several open-ended questions as the moderator asked in-depth questions to clarify the answers. Transcripts were analyzed by 2 researchers (LvB and BS) in order to discover any major themes across participants.

Analysis discovered 7 themes that the at-risk individuals used in deciding whether or not they would participant in a prevention trial:

• Symptom severity was an important factor in an individual’s decision to participate or not. If the patient had minor symptoms, they were less likely to agree to the trial. Conversely, if a patient had severe symptoms, they were more likely to participate in hopes of symptom resolution.
• Risk assessment was categorized into 2 groups: personal risk of RA development and the estimated severity of a patient’s RA. Both factors contributed to whether or not a patient would participate in the trial. For example, low risk would be considered a barrier, whereas the possibility of severe symptoms might persuade an individual to enter the trial.
• Treatment options was split into 2 groups: treatment of symptoms and feeling of being monitored. Patients who believed the medication would resolve their symptoms were more open to participant. Being closely monitored could provide quick and thorough care by medical professionals.
• Feeling of acknowledgment was a facilitator, as symptoms and concerns would be taken seriously.
• Trial medication was split into 4 subsects: fear of using the medication, preferring to try natural remedies instead, a reluctance to statin use, and the medication’s effectiveness. The first 3 were seen as barriers, whereas the hope that the medication could prevent RA was a facilitator.
• Study burden was a barrier, with issues ranging from time investments and undergoing study procedures.
• Altruism was deemed a facilitator, as it allowed individuals to contribute to society and help prevent others from developing the disease.

There were 2 additional factors that did not fit under the aforementioned themes that played a role in a patient’s decision: the attitude of the physician and being well-informed. Reasons for the former included the physician’s confidence and enthusiasm about the research, while the latter dealt with receiving information about the medication, including side effects and RA development.

The study was limited by the small group of participants, however, it was strengthened by including those who were already approached about prevention trials, as opposed to a hypothetical scenario. Investigators also ensured varied opinions by including both at-risk individuals who chose to participant in prevention trials as well as those who declined.

“Our results suggest that inclusion of RA-risk individuals can be improved by implementing strategies such as optimizing education about personal risk, trial aim and trial medication, explicitly addressing potential participants’ misconceptions and concerns, using tools to improve information provision, limiting study burden by condensed trial design, and encouraging physicians to mention trial participation,” investigators concluded. “Addressing these factors could facilitate inclusion in trials aimed to prevent RA onset, potentially improving prognosis and reducing overall RA disease burden.”

Reference:

van Boheemen L, Ter Wee MM, Seppen B, van Schaardenburg D. How to enhance recruitment of individuals at risk of rheumatoid arthritis into trials aimed at prevention: understanding the barriers and facilitators. RMD Open. 2021;7(1):e001592. doi:10.1136/rmdopen-2021-001592