Participant selection and recruitment

We used a purposive sampling strategy, a qualitative sampling technique used to select participants with experience of the phenomenon to provide an in-depth understanding. We recruited physicians in Canada who had treated adult patients with Ig in Canada through organizations representing relevant specialties in consultation with CBS Stakeholder Engagement. See Table 1 for a list of organizations that received the recruitment email invitation; prospective participants contacted the PI to arrange interview.

Download:

• PNG
  larger image
• TIFF
  original image

Table 1. List of organizations that received the recruitment email.

https://doi.org/10.1371/journal.pone.0354817.t001

Data collection

Interviews took place on Zoom from April to September 2024. They were conducted by KH, the lead researcher of the study, who has a PhD in sociology and is a Scientist with CBS, and lasted 30–80 minutes. The semi-structured interview guide was iteratively refined across the interviews.

Participants were asked questions about their practice, relationships with other specialists, the illnesses they treat, their knowledge of Ig and what they communicate to patients about this treatment, and their process for prescribing Ig. Participants were also asked policy questions around availability of Ig, guidelines, and the blood service’s formulary development process for making decisions about which products are covered by health insurance in Canada. Participants were given a short explanation about how Ig is distributed in Canada’s health system (Fig 1: Short description) and asked to reflect on this system.

Download:

• PNG
  larger image
• TIFF
  original image

Fig 1. Short Description about is distributed in CanadaIg’s health system.

*Note: CADTH has been renamed Canada’s Drug Agency (CDA-AMC).

https://doi.org/10.1371/journal.pone.0354817.g001

Data analysis

KH, the lead researcher, and UM, a Research Assistant on the study conducted an iterative interpretive thematic analysis [16] involving a careful reading of transcripts, coding in NVivo14 (a qualitative data software), and continual reflection about the data in relation to literature in the field and our own perspectives and roles within this system. We generated themes on different aspects of clinician experiences with prescribing Ig as a treatment, which were then discussed and developed with a third member of the study team, QG. Our analysis focused on understanding the meaning conveyed by participants about topics explored in the interviews. UM, the research assistant, conducted initial line-by-line coding and wrote research memos summarizing each participants’ account organized by their answers to the interview, such as conditions they treat, knowledge of Ig, etc. The lead researcher and the research assistant then reviewed the codes and started to organize them into themes, while also adding contextual information from the memos offering more depth about each participants’ account. Broad thematic categories were developed from this process after conducting eight interviews (research on Ig, patient awareness of Ig, care of patients with Ig, cost of Ig, and access to Ig). To further understand the extent to which these themes remained meaningful with more participants, we then conducted four more interviews. Following this, we reviewed the final transcripts in relation to the themes until we gained a sufficiently comprehensive understanding of the issues raised in the data to offer meaningful qualitative insight about this nascent area of study, a process to achieve what is called meaning saturation [17]. These broad themes were then discussed and refined by the research team and put into dialogue with the literature informing the study to generate our analysis. Given our focus on the participants’ decisions about prescribing, we use the concept of ‘orientation’ sociologically to mean the ways in which beliefs, values and experiences continually inform how physicians approach their clinical practice. Our analysis seeks to situate the prescribing physician a person who both draws on their fundamental beliefs and values, and responds to the existing context, to navigate the complex field of prescribing this particular therapy. All 12 participants are represented in the analysis. Each orientation was derived from patterns of reasoning that recurred across the full sample and contributed to the construction of these orientations. Quotations were selected to illustrate each analytic point in participants’ own words.

This analysis process also involved reflection about the fact that the lead researcher is an employee of CBS, and recruitment was facilitated by CBS. Thus participants could have been more reserved about offering critical feedback about this organization and also particularly sensitive to defending their role as good stewards of the blood supply. Given that this population is not easy to reach, the interviewer’s role also could have been the factor that facilitated trust and access to the participants. The other members of the research team provided an outside perspective to help contextualize this data and think about how this is a particular sample of the broader population of prescribing physicians, a point we raise in the limitations section. Authors resolved disagreement about analysis through dialogue. We offer thick description and the use of verbatim quotations to establish the credibility of our analysis [18].

Concern and uncertainty about prescribing Ig

Despite treating patients with Ig, participants expressed continued uncertainty about why Ig worked better in some patients over others with the same disease, why some patients responded better to subcutaneous immunoglobulin (SCIg) or to intravenous immunoglobulin(IVIg), why certain patients had side effects while others did not, or how long they should treat a patient with Ig. Participants also expressed uncertainty about optimal dosage and frequency. Thus, they acknowledged uncertainty and explained that managing this uncertainty required continual interaction with the patient, paying careful attention to how the patient responded to treatment.

This uncertainty did not come from a lack of training, but rather from a lack of research on Ig as a treatment – on the mechanisms, side-effects, and other indications that could require Ig. Further, given the complexities around diagnosing rare conditions, which do not always have a straightforward clinical diagnosis pathway, specialist participants had experience treating patients who were first misdiagnosed or had gone long periods without diagnosis. One participant explained,

“Immunology as a whole; you might get one or two courses in medical school. You can; you could go very, very deep into immunology and still not understand it. […] The immune system is complicated for many people. And I wouldn’t expect most physicians to truly understand the complexities of it. Including family physicians” (P1).

Participants described situations where the patient received a diagnosis in their community, were referred to another specialist for their condition, and received ineffective—and in hindsight, inappropriate—treatment. These difficulties in diagnosis could lead to a delay in treatment, prolonging patients’ symptoms, and were exacerbated in rural locations and areas underserved by specialists with experiences treating these rare conditions. Further, some patients received Ig, but did not understand that it could be for a limited duration. Participants explained that once a patient was on Ig, it was difficult to suggest that the treatment was no longer necessary. A participant explained that they struggled with telling patients they should no longer be on Ig:

“I do find it a bit frustrating for many reasons, most, the primary one which is resource allocation but also, the message that a patient gets when they’re on a treatment that they don’t need, is very hard to un-tell. So, it puts you in a very awkward position” (P8).

Acknowledging that many family physicians had not even heard of some of these rare conditions for which Ig was indicated, one participant said they provided education to family physicians on red flags that would require a referral to their specialty. Participants also tried to communicate with physicians in their network about appropriate use of Ig.

Good stewardship of a scarce resource

Participants understood Ig as a scarce and expensive resource. They learned about the expense of this treatment in their training, and all said they made decisions about prescribing carefully, considering the cost of this treatment. Some discussed cost with patients to engage them in cost-effective care. Others refrained, believing that the medication was necessary for their patient, and that a discussion of cost could cause undue stress. Others exercised caution through discussions with their patients about dose and duration of treatment – depending on the underlying condition, some explicitly communicated to patients that Ig is a bridging rather than ongoing therapy. One participant said if they have a patient that has been on a high dose of Ig for ten years, they will suggest moving to incrementally lower doses. Participants also thought about cost of Ig as a treatment in relation to alternative medicines that are as effective and not as expensive. One participant explained, they do not hesitate to prescribe Ig if it is appropriate. At the same time, “if there are less expensive options that don’t necessarily have more side effects, then I, you know, I try to keep that in mind” (P4).

The orientation toward Ig management as a form of good stewardship arose most obviously when the interviewer introduced information about how Ig is distributed in Canada (See Fig 1) and asked participants if they were familiar with this process, and whether they thought that it served the needs of patients. Given our recruitment strategy, many participants were familiar with the process, and some had even been involved in developing policies to address potential shortage of Ig in Canada, as well as other policy issues related to management of this treatment such as payment for plasma. Some identified as not only a physician but as a resource utilization steward for blood products. Or as one participant put it, they needed to be “reasonable gatekeepers of this public resource” (P2).

They acknowledged that good stewardship of Ig required more communication and training among physicians. Some participants said they tried to communicate with other specialists in their area about not using too much Ig, and using it in the right clinical context. For example, one participant suggested that community neurologists should be calling specialists who are more connected to the academic community to seek guidance on the appropriate us of Ig:

“I’d like to communicate that, we’re using too much of it, and, we should be using it in the right clinical context. So, if you’re not sure about the medication, just call us, and we can have a conversation about it” (P5).

In some provinces, SCIg has been introduced as an effort to mitigate issues of cost and improve access. Some participants saw this modality as advantageous for patients because hospital-based infusions are inconvenient and it was potentially risky for a person who is immunocompromised to enter a hospital for infusion. Some also thought it was less costly for health systems. One participant started to recommend SCIg because they noticed that IVIg was having an impact on infusion capacities in their hospital: “A lot of the patients have to come in, like, on a monthly basis. And, so, that’s a huge impact on the infusion capacities of the hospital" (P11). Many were trying to determine how the introduction of SCIg fit into the broader landscape of the health system, and also figure out whether and how it should be integrated into the care they provide.

Advocacy for access to treatment

Participants in this study were very much aware of how their practice was a part of a broader health system, which is dynamic and political. They reflected on the impact of the cost of increasing use of Ig on healthcare budgets, access to specialists for people in rural and remote areas, and training of primary care physicians. Further, they often acted as advocates for their patients to get access to Ig by engaging with various levels of hospital administration and government. They were engaged at a policy level with respect to management of Ig as a blood product, being good stewards, and participating in policy planning about issues like potential shortage of Ig. One participant explained:

“As a haematologist, I’m advocating for resources for my patient, and then as a transfusion doc, of course I’m advocating for the patient, but then I’m also advocating for the system and trying to balance those things, and I think that that’s where things like IVIg come in. I think you have more contact with the Ministry who’s concerned about, you know, the cost of IVIg over time” (P11).

This kind of advocacy required participants to be responsible for not only patients but also resource utilization.

Participants indicated that they thought carefully about how their role was intertwined with political matters. Our description of the process for distributing Ig indicated that part of this process includes deliberation about whether any new product would bring “good value to tight health-care budgets” (see Fig 1). Some participants cautioned the use of that phrase, pointing out that “good value” had different meanings depending on where one is situated in the healthcare system (as a regulator, a government agency, a physician, a patient, or a pharmaceutical company). Some expressed concern about the role of pharmaceutical companies in these processes who lobby to have their product covered on the formulary. For example, one participant had been privy to a situation where a company was arguing that their product should be covered because it would compete with IVIg, but they had not done a head-to-head trial. Further, participants suggested the phrasing around “good value” inherently assumed scarcity: “I think when you use the word ‘tight healthcare budgets,’ it already suggests that we’re coming from a place where we’re in scarcity” (P5). The participant explained, “So, it should maybe be something like, ‘good value to our sustainable long-term healthcare budget,’ or something like that. You know, using words that are more neutral, because this word is not neutral” (P5).

Several participants had been part of discussions about potential shortages of Ig, because there was a need to make policy decisions about how to prioritize medications in that scenario. One participant explained that physicians learn about procurement, availability, and manufacturing because of efforts to plan for potential shortage:

“We’re part of the discussion when those threats loom, I think appropriately, and it’s part of, like, trying to gauge who, who really needs it. Who could wait an extra month. Uh, thankfully, I guess we’ve just been very lucky that it hasn’t materialized where we’d have to start to triage in that way” (P6).

Even outside of the context of a potential shortage, not every IVIg product was approved in the national formulary, and sometimes a product was phased out of the market. This could be disruptive for patients, A participant explained:

“I think inside the blood banks and the transfusion medicine, they have to manage that much more where,[…] they’re changing products, [patients are] not getting the same product over all the time, and, those patients who are, have reactions that some products, or have trouble, trouble tolerating some" (P7).

Physicians acted as the gatekeeper to treatment, and while they were not always at the table for decisions about coverage, they had to manage care for patients when a treatment became unavailable, or when treatments changed because of a formulary decision. They therefore became invested in decisions about coverage and allocation of resources.

Part of playing an advocacy role for their patient involved navigating a complex health system with multiple players. For instance, the introduction of SCIg came with new players and systems that participants had to understand and manage. Participants articulated that the availability of SCIg removed the need for patients to come to hospital for infusion, but some expressed concern about how that shift would affect dosing, benefits, harms, and effectiveness, questioning whether the shift was driven by clinical need, health system priorities, or commercial interest. A participant articulated their uncertainty about what is driving this change:“I don’t know where the money is going. I don’t know where the profit’s going. I don’t know where the push is” (P3). They described a patient with an immune deficiency who could get a lower dose of Ig through SCIg at home, and not be exposed to potential infections at the hospital. While this is advantageous in some ways, the participant worried about the potential risk of administering high-dose Ig injections at home and the unknowns around the impacts, benefits, or harms of the subcutaneous formulation.

Participants recognized the need for support in the community to help patients transition to SCIg and administer injections at home: “You kind of need a program behind it, and, I haven’t quite figured out who that’s gonna be for all of the patients that we have here” (P6). In response to this need, participants explained that the pharmaceutical companies that produce SCIg had created and funded “patient support programs,” which included injection training, while simultaneously encouraging physicians to use their brand of SCIg. Some participants were cautious about those relationships with pharmaceutical companies, indicating that they preferred to pay attention to the evidence and expressing concerned about the effectiveness of these programs. One participant said working with these programs was challenging because they required a high degree of coordination, including detailed direction about Ig administration from the prescribing physician. This could be challenging; for instance, this participant said neurologists often did not have all of the relevant information about the patient, as it was predominantly a nursing scope of practice, and wished instead to work with specialist nurses in the publicly-funded system. Another participant echoed this concern indicating that many of their patients had not transitioned to SCIg because there were too many difficulties transferring to a manufacturer-led patient support program. This participant emphasized that because patient support programs are brand exclusive, patients had to move from a nurse they trusted to administer IVIg in the hospital, to a program that required them to stop working with that nurse and potentially switch products.

“Because the patient support programs are product-specific, the patients weren’t able to just keep working with the same nurse, they had to switch programs entirely, and so that was super-disruptive to them. They kind of had a relationship with one person, and then, were no longer able to work with that person” (P2).

Participants described the burden of the transition to SCIg not just on patients, but also on their practice’s office, given the coordination involved with the company, or multiple companies’ patient support programs. Some suggested it would be most effective to have a nurse who worked with the immunodeficiency program in the hospital to help coordinate transition to SCIg because they had the condition-relevant expertise, injection skills and training and could provide the social support that was necessary to manage treatment: “the problem with SCIg is if, is it really requires more, potentially more of an infrastructure […], to deliver it, because it’s being delivered at home, that means it requires patient training, and education” (P7). For example, the transition required careful consideration of whether the patient had someone who could work with them to do the injection or the hand dexterity to do it on their own.

Limitations

This study represents a small sample of experts from different fields of medicine, practicing in Canada. Their perspectives and experiences differed by disease area, which is not explored here because of the limited sample but represents an area for future research. Given that they were recruited with the help of our colleagues in CBS stakeholder engagement, and that the lead author and interviewer works for CBS, this sample is potentially unique. Participants were very aware of the policy landscape for managing Ig in a potential shortage, and some described themselves as good stewards of blood products in Canada. Despite efforts to reach physicians across the country, another limitation is that participants were from Ontario, British Columbia and Alberta, which only represents three of Canada’s thirteen provinces and territories, and specifically does not cover Quebec, which has a distinct healthcare jurisdiction and blood operator.