By Deborah Borfitz 

March 23, 2021 | AbbVie is developing a patient burden algorithm to quantify the onus of trial-related procedures on study participants, according to Allam Fakhoury, PharmD, the company’s head of portfolio design and execution, at a presentation he made at last week’s Summit for Clinical Ops Executives (SCOPE). The pilot scoring system was created using responses to an online survey completed by about 700 patients in Inspire health support communities for rheumatologic disease, dermatologic disease, inflammatory bowel disease, hematological malignancies, and solid tumors. 

The survey data have strong internal consistency and provide demographic information as well as sentiments about the logistics of participation, patient-reported outcome (PRO) questionnaires, and procedures such as the taking of vital signs, lab/blood work, noninvasive (e.g., biomarker/genetic test) and invasive (e.g., bone marrow aspirate) procedures, and imaging, says Fakhoury. While the survey data overall was highly skewed, procedures within each category tended to have a similar distribution of burden score, he adds. 

The algorithm was beta tested on 20 AbbVie protocols (immunology and oncology indications) to calculate the median burden score for historical clinical trial protocols, Fakhoury continues. Next steps are to understand the relationship between burden scores and study-level metrics such as cost, enrollment duration, the screen fail rate, the dropout rate, the number of sites, and the number of procedures. 

A data dictionary is being built to automate mapping of the correlations, says Fakhoury. More than 200 protocols have been identified for a potential prospective study looking at the relationship between the patient burden score and the patient-level metrics once findings of the retrospective analysis have been fully evaluated.

Defining Burden 

The Medidata Patient Burden Index (PBI) was used to evaluate measurement parameters, he says. The PBI algorithm evaluates the level of anxiety, pain, and invasiveness caused by a procedure, exposure to harmful substances (chemotherapy) or radiation, required hospitalization and time, number of questions or items in a survey or interview, and the type of questionnaire or survey used. 

The contract research organization ZS helped AbbVie define the burden score based on four categories of factors identified prior to the pandemic: procedural (effort, time commitment, anxiety, and pain), convenience (number of visits, travel distance, type of transportation, days of work missed, and arranging for child care) lifestyle (restrictions associated with diet, exercise, smoking, and alcohol consumption), and caregiver considerations (enrolling in the study, recording data and notes, helping administer study drug, and providing transportation and childcare). 

As defined by AbbVie, trial-related patient burden is a “framework of factors that may impact how a patient perceives, interprets, and experiences participation in a clinical trial,” he shares. The company’s objective is to “create a methodology for quantifying protocol-level, or study-related, patient burden from the scheduled assessments.”  

Inspire developed and fielded the online survey for U.S.-based patients, Fakhoury says. The master survey captured categorical data for demographics, logistics, procedures, and PRO questionnaires. Survey questions were indication-agnostic, he adds.

Survey Says … 

Patient sample demographic data indicates that Inspire’s network is predominantly female (72% of patients surveyed), says Fakhoury. Indication-specific data followed a similar sex distribution, excepting those with solid tumors where there was a balance of males and females. Somewhat unsurprisingly, the immunology patient population was younger than the oncology patients. 

One unexpected finding was that solid tumor patients mostly had bladder cancer, which skewed results, he says. Inspire’s partnership with the Bladder Cancer Awareness Network was likely a contributing factor. 

In terms of logistics, ZS looked at travel and transportation burden while AbbVie examined distance to clinical trial site, travel duration, visit duration, and visit frequency, says Fakhoury. Most patients (82%) indicate the maximum time they want to spend traveling to a research center is under one hour; three patients thought greater than three hours was acceptable.

Previous research (Getz et al., 2019) has found the typical time participants are willing to spend at each study visit is most often one to three hours, he says. AbbVie has found that the distance most patients are willing to travel to get there is between 0 and 40 miles. Less than an hour is by far (79%) the most acceptable travel time duration. Two to four hours is the sweet spot (82%) for the average visit duration for the first three months of a study, akin to findings in the literature.

Overall, ZS and AbbVie data are consistent—80% of patients were willing to spend an hour or less traveling to a trial site, and one in three patients is willing to attend more than one visit per week in the first three months, Fakhoury says. Oncology patients, or at least those with bladder cancer, are willing to travel long distances.

Survey findings indicate that stool collection has higher burden among ulcerative colitis patients compared to urine and blood collection, he says, and a chest X-ray has a much lower burden relative to a CT, PET, or MRI scan. Among rheumatoid arthritis patients, procedures that involve lab/blood collection and those that are invasive are not similarly distributed in terms of burden. 

The median burden score for the taking of vital signs, lab/blood work, and noninvasive procedures is rated similarly across therapeutic conditions, Fakhoury notes. In the imaging category, patients with solid tumors, rheumatic joint disease, and malignant hematologic tumors find imaging to be more burdensome. The burden score for lab/blood work and imaging are similar for Crohn’s disease/ulcerative colitis patients and those with psoriasis/atopic dermatitis, while invasive procedures are ranked highly burdensome across the board. 

PRO questionnaires stand out as particularly burdensome, contrasting starkly with vital sign burden scores, he says. A similar discrepancy is seen when comparing vital sign burden to the overnight hospital stay score among the two cancer patient groups.

The median burden score for spending two hours answering a PRO questionnaire is similar across therapeutic areas, excepting the patients with solid tumors—again, due possibility to the preponderance of bladder cancer patients in that category, says Fakhoury.

A total burden score calculation would require different elements, he concludes, including study-specific burden for convenience, lifestyle, and caregiver involvement. These would need to be captured prospectively.

Among the key themes emerging from patient quotes is that transportation to a clinical trial site, distance traveled, and cost of participation (including parking and lodging) are important, as is compensation for participation, Fakhoury says. Whether food and drink are offered during study visits, childcare is available, visits can be flexibility scheduled, trial data is made available upon study completion, and gratitude is expressed for helping other patients are among other factors potentially impacting burden-of-participation perceptions.