Survey of Patients with Cystic Fibrosis and Caregivers Decisions Regarding CFTR Modulators

Ashish George, Beth Smith, Gregory S. Sawicki, Danielle Marie Goetz
1. Dept of Pediatrics, University at Buffalo, Buffalo, NY, United States.
2. Dept of Psychiatry, University at Buffalo, Buffalo, NY, United States.
3. Dept of Pediatrics, Boston Children’s Hospital, Boston, MA, United States.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators are a novel approach to CF management that has become more readily available chronic CF therapies for certain populations of patients with CF. A cross-sectional survey of adults with CF and caregivers of pediatric patients with CF was done in two CF Centers to better understand the decision-making process including the potential influence of social media, CF care-teams, and family members on their decision whether to begin a CFTR modulator. For the 90 participants, the most common influences in the decision to start modulator therapy were the CF providers/care teams (n=63), parents (n=49) and individuals with CF (n=27). The most impactful influence in the decision-making process were providers/care team (n=47) and parents (n=18). Social media was an influence for only 12 respondents, with an overall positive impact. Information from the CF Foundation was an influence for 12 participants and the main influence for 6 participants. The most common reasons for stopping LUM-IVA were having TEZ-IVA as an option (n=25) and side-effects (n=15). Family and CF clinicians were the two main influences on the decision to initiate modulator therapy. CF clinicians were seen to be the most influential source. Social media had less influence on the decision-making process than expected despite the wide presence of the CF community online.

The introduction of lumacaftor-ivacaftor (LUM-IVA) (Orkambi, Vertex Pharmaceuticals, Boston, MA) in 2015 provided a new treatment option for those with two copies of F508del mutation in CFTR. The uptake of LUM-IVA was not as robust as seen with ivacaftor (Kalydeco, Vertex Pharmaceuticals, Boston, MA) for CFTR gating mutations1. Tezacaftor-ivacaftor (TEZ-IVA) (Symdeko, Vertex Pharmaceuticals, Boston, MA) was introduced in 2018 as an alternate option for F508del homozygotes ≥ 12 years of age. Phase 3 studies showed absolute improvements in FEV1 of 4% from baseline with TEZ- IVA2. Phase 3 studies with LUM-IVA showed an absolute improvement in FEV1 of 2.6- 4%3. Given similar effectiveness profiles and side-effect profiles2,3, it is important to explore the decision-making process in deciding which medication to start. Further, influences from family and social media affect the decision making process in healthcare, especially with regards to starting new medications 4 5.
This study aimed to better understand the stakeholders involved and the influences on the decision-making process for adults with CF and caregivers of children with CF regarding initiating or discontinuing use of either LUM-IVA or TEZ-IVA.

A cross-sectional survey study was completed at two CF centers in Buffalo, NY and Boston, MA over a seven-month time period between August 2018 and February 2019. Eligible participants were adults (≥18 years) with CF or parents/legal-caregivers of children ages 6-17 years old with CF with two copies of F508del mutation who were clinically eligible for either LUM-IVA or TEZ-IVA and had previously taken or currently taking either medication. Patients and families had presumably been given information about one or both medications, but the information was from their CF care teams and not standardized. Of note, TEZ-IVA had not yet been approved for 6-11 year-olds at the time of the study. Informed consent was obtained from all participants in accordance with institutional IRBs.

Data was collected via a 24 question non-identifying survey administered electronically during clinic visits or hospitalization (Table 1). Demographic information was collected, including age, highest education level, and income level. Subjects were asked their most recent FEV1%-predicted and number of IV antibiotic courses in the last year. Those taking either LUM-IVA or TEZ-IVA were asked length of treatment with the respective medication, information heard about the medication prior to starting, source of the information, aspects of the treatment discussed with their provider, parties involved, most impactful party and impact of social media on the decision-making process. For survey questions 15 and 16 which inquired about parties involved in the decision making process for LUM-IVA start, the choice of “parents” was applicable to adults with CF, whereas “grandparents” and “child with CF” were applicable to parents of children with CF who were answering the survey. Those who had switched from LUM- IVA to TEZ-IVA were asked the reason(s) for switching. Those eligible for TEZ-IVA who did not switch were asked the reason(s) for not switching. Respondents were not limited to one response for influences in the decision-making process or reasons for stopping and/or switching.

Data analysis:
Counts and frequencies were summarized for each independent variable.

There was a total of 90 participants (60 adults with CF and 30 caregivers) in the study: 49 from the CF center in Buffalo, NY and 41 from the CF Center in Boston, MA. Participants were pooled for analysis. Results of influence of social media, provider, family and the decision to switch based on age, income, FEV1, and education are summarized in Table 2.
The most common influences in the decision to start a medication were CF clinicians/care teams (n=63), parents (n=49) and child with CF or individual with CF (n=27). The most impactful influences in the decision-making process was CF clinicians/care team (n=47, 52%) and parents (n=18, 20%) (Figure 1).

Social Media:
Social media played a role in the decision to start LUM-IVA for 12 participants. The influence was “positive” for 4 participants towards LUM-IVA and “somewhat positive” for 5 participants towards LUM-IVA, based on a 5-point Likert Scale. Information from patient forums/blogs influenced 9 participants.
Educational level did not have an influence on whether social media impacted decision making. Similarly, FEV1 (% predicted), age, and income also did not impact the influence of social media.

Provider Impact:
Most of the respondents with postgraduate degrees were influenced by the CF provider (n=18, 90%). Our data suggests the following trend: those with lower FEV1 (<70%) were more likely to be influenced by the CF provider (n=15, 58%) compared to those with FEV1>70% (n=31, 50%). Income did not have an impact on being influenced by a provider. The data also suggests a trend for adults with CF being more influenced by the provider (n=33, 55%) than the parents of children with CF (n=14, 46%).

Family Impact:
Respondents with less than a postgraduate degree were more influenced by family than those with a postgraduate degree. Those with an FEV1 ≥ 70% were also more likely to be influenced by family. There was no relationship between income or age and family influence.

Decision to Switch:
There was a total of 45 participants who switched from LUM-IVA to TEZ-IVA. Respondents with some college or a college degree more often switched from LUM-IVA to TEZ-IVA (n=27, 56%). 69% of those with FEV1 <70% switched from LUM-IVA to TEZ- IVA compared to 44% of those with FEV1 ≥ 70%. FEV1 of 70% is based on American Thoracic Society (ATS) guidelines for categorization of lung disease severity with 70% being the cut off for mild disease and moderate disease6. There was no noticeable difference in the decision to switch based on income. Adults with CF were overall more likely to switch compared to children based on parental response, with the largest group aged 26-35 years old. Parents of children with CF aged 36-49 years old were also more likely to have switched their child’s medication than those in other age groups. There was a total of 61 participants on TEZ-IVA. The most common reasons for the 45 participants who switched from LUM-IVA to TEZ-IVA were “My doctor felt it would be a better option” (n=27) and “I heard better results about Symdeko” (n=24); although some stated side-effects (n=10)(Figure 2). The most common reasons for the 51 participants who stopped LUM-IVA were having TEZ-IVA as an option (n=25) and side- effects (n=15). Within this group of 51 participants, there were 21 participants who did not chose TEZ-IVA as a reason for stopping LUM-IVA. The most common reason for stopping LUM-IVA for this group were side-effects (n=15) and LUM-IVA not being effective for them (n=8). Of note, there were 18 participants who never took LUM-IVA.

The decision to start a CFTR modulator is multifactorial. Not only do the individuals have to take into consideration risks/benefits of the medication, cost, drug interactions, but they must also balance the influence of family, spouse/partners, other individuals with CF, health care providers and online sources. The internet has provided a forum for interaction for various disease communities, as well as a source of information about new treatment options7,8. Information from online sources is often used to supplement the information received from providers or other medical experts7, or used as a means of synthesizing information when faced with a difficult medical decision8. Adults 18-24 years old were more likely than any other age group to utilize social media in obtaining medical information8. Given the contact limitations of the CF community, the internet and social media provide a platform for both families and individuals with CF to share about their disease. A sizable influence of social media on the decision-making process to start either LUM-IVA or TEZ-IVA was expected. Social media, however, had a minimal role in the decision-making process with only 13% (n=12) of participants stating that social media played some role in their decision making; only 1 participant stated it had the most impact. The overall influence of social media was seen to be positive/somewhat positive in favor of CFTR modulators. Though this data suggests that the influence of social media was not as profound as anticipated, there might have been indirect, unaccounted for influences from social media that may have supplemented or strengthened information received from providers.
Providers/care teams impacted the decision of many participants. 63 participants (70%) stated that providers/care team played some role in the decision-making process with 47 participants (52%) stating that providers were the most influential participant. This provides support for the notion that providers have more influence on their patients than is many times felt, as opposed to being an advisor9,10.
Family influence on the decision making process had much less of an impact than expected, given that research in adults has shown that a majority of chronically ill adults have some level of family involvement in medical decision making with about a third of patients using family, friends or coworkers as the primary source of health information9.
The medical decision making process has veered away from the paternalistic model of provider dictating management to more of a shared decision making model11. This dynamic is particularly highlighted when there are multiple viable treatment options available11. In those that switched modulators, 27 participants (60%) stated that their provider feeling it would be a better option was the reason for switching, followed by 24 participants (53%) stating that hearing better results about TEZ-IVA was the reason.
The Cystic Fibrosis Foundation (CFF) has been involved in not only establishing standards of care for patients with CF but also helping fund research for novel medications. In 2017, the CFF spend $16.9 million on public and professional information and education12. Given these efforts, it was expected that information from the CFF would have had more impact on the decision-making process. Instead, what was seen was that the information from the CFF played some role in the decision-making process for 12 participants (13%) and was the most influential impact for only 6 participants (6.6%). However, this does not account for any indirect role that information from the CFF might have on both providers/care teams and subsequently patients and families.
As new modulators continue to be approved for the management of CF13, patients and families will continue to be faced with the challenge of which modulator to choose as part of their therapy. The results of this study provide a better understanding of the decision-making process this population utilizes in the selection of a modulator therapy.

This study was limited by the small sample size preventing statistical significance of data. Further, the study was only able to be conducted at two centers, limiting generalizability of the data. The study was a self-reported retrospective study prone to recall bias. The study also does not account forthe indirect impact of information from the VX-661 has on providers and on patients/families. Similarly, the influence of parents/grandparents might be confounded by the influence of the care team or provider on them, making it difficult to distinguish fully amongst the various influences.

Future Directions:
Further prospective investigation into the influence of the provider in the decision-making process may help shed light into what helps foster positive and therapeutic provider-patient relationships. Qualitative research approaches with open-ended questions or in-person interviews would potentially provide greater insights than those attainable via a pre-populated response survey.

CFTR modulators are an important class of therapies which will likely form the backbone of future CF care for many. The decision to start a CFTR modulator can be challenging. Despite our expectation that the internet and social media may have a strong influence on a patient’s medical decision making, the advice of health care providers remained the most important influence. It is important to continue to improve the shared decision-making model and augment tools for patient-provider communication in keeping both patient and families central in the decision-making process around these novel therapies.