What factors could influence physicians' management of women of childbearing age with chronic inflammatory disease? A systematic review of behavioural determinants of clinical inertia

Chronic inflammatory disease (CID), including chronic rheumatic diseases (CRDs) such as rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), as well as other chronic conditions such as inflammatory bowel disease (IBD; Crohn’s disease and ulcerative colitis) and psoriasis (PsO), commonly affects patients during their reproductive years [1‐5]. For women considering pregnancy and their treating clinician(s), there arise a number of concerns and uncertainties regarding the impact of active disease and continuing medication on conception, pregnancy outcomes and breastfeeding. This may create an environment vulnerable to ‘clinical inertia’.

Clinical inertia has typically been described in health conditions which take a ‘treat-to-target’ approach, such as Type 2 diabetes, hypertension and dyslipidaemia [6‐8]. It was initially defined by Phillips et al. in 2001 as “failure of health care providers to initiate or intensify therapy when indicated” [9], but it has since been suggested that it be expanded to encompass other behaviours, such as prescription of preventative therapies and management of risk factors and complications [10]. In the setting of multiple sclerosis, an immune-mediated neurological disease with a pattern of flare and remission, clinical inertia has been defined as “lack of treatment initiation or escalation when there is evidence of disease activity” [11]. As a consequence of clinical inertia, patients can experience suboptimal management of their condition which carries increased risk of subsequent adverse health outcomes.

Treat-to-target has been established as a guiding principle for the treatment of patients with RA [12] and this approach has been shown to convey better outcomes compared with routine care [13]. Nevertheless, it seems that although some elements of treat-to-target are widely used, full implementation appears to remain uncommon [14].

Clinical inertia has been associated with behavioural factors such as mental heuristics and biases, attitudes to risk and emotion [15]. Humans use cognitive shortcuts (heuristics) to make a large number of decisions efficiently and effectively on a daily basis; however, when used inappropriately, these heuristics become biases, leading to suboptimal outcomes [16]. The involvement of heuristics and biases in medical decision making have been characterised by two systematic reviews [17, 18]. It appears that the use of heuristics in inappropriate contexts increases when the decision being made is associated with a degree of uncertainty or risk [18]. Clinical inertia also appears to be more prevalent when the treatment decision in question involves uncertainty or risk in terms of the effect on the patient’s outcome.

It was hypothesised that in the management of women of childbearing age with CID, clinical inertia could encompass not only a failure to initiate or escalate treatment, but also inappropriately discontinuing treatment (when it is required for disease control) due to uncertainty surrounding the risk of using of pharmacological agents during conception, pregnancy and breastfeeding. Therefore, clinical inertia and associated heuristics and biases may impact clinical decision making in the management of women of childbearing age with CID, leading to suboptimal disease management and patient outcomes. The objectives of this systematic review were to address the following research questions using a behavioural science approach: Has clinical inertia been described as affecting physicians' management of women of childbearing age with CID? What behavioural factors have been described as driving clinical inertia in this setting, such as the emotional context and physicians' attitudes to risk? Does the literature indicate that heuristics and biases are influencing clinical decision making in this setting?

Due to the qualitative nature of this literature review, barriers to the pharmacological management of women with CID identified were coded for thematic analysis using two inter-related behavioural models; the COM-B (Capability, Opportunity, Motivation, Behaviour) model and the Theoretical Domain Framework (TDF). The COM-B model proposes that human behaviour occurs due to the interaction between three necessary conditions: capability, which is the psychological and physical ability to enact the behaviour; opportunity, which can be both the physical and social environment that enables the behaviour; and motivation to perform the behaviour in preference to competing behaviours, which can be reflective (conscious, effortful, deliberative) and automatic (habits, emotional responses, impulses) [19]. The TDF has also been used extensively to understand behaviour across a wide range of healthcare and clinical settings. It contains 14 domains, which can be mapped against the COM-B model to gain a more ‘granular’ understanding of the determinants of the behaviour [20].

“The desire to start a family adds additional complexity to management decisions preconception, during pregnancy and following delivery given the lack of safety data and potential teratogenicity of available therapies” [21].

(For all selected quotations please refer to Additional file 1: Tables S4–S7)

No papers were identified that specifically investigated and thus confirmed the presence of clinical inertia in women of childbearing age with CID. However, an overarching opinion in many of the papers reviewed (and appeared to be true across both rheumatology and gastroenterology specialties) was that women of childbearing age with CID are considered complex and challenging cases to manage by clinicians [1, 21‐26]. From this literature search it was possible to identify numerous factors that may be influencing optimal decision making in the management of CID patients and contributing to this label of ‘challenging’. By applying the COM-B model, it was possible to map these factors to all three domains – capability, opportunity and motivation – allowing identification of barriers and drivers that may be influencing clinician behaviour, and how these may contribute to heuristics and biases, and ultimately clinical inertia. Figure 1 summarises the overarching findings of the literature search as mapped onto the COM-B model.

“Of paramount concern are questions about the effect of the disease on a woman’s ability to conceive and carry the pregnancy safely to term, as well as the effect of the disease and its therapies on the health of the fetus” [25].

The fear of a medication’s effect on both the mother and fetus may encourage clinicians to inappropriately discontinue medication or fail to optimise treatment. In the case of IBD and CRD, uncontrolled disease activity is known to increase time to pregnancy and potentially negatively affect pregnancy outcomes [2, 3, 5, 34, 52‐54]. However, how well this is understood or recognised by clinicians in the clinical management of these patients is unclear. Pregnancy therefore represents a somewhat unique situation to clinicians, who may not understand the risk associated with active disease, and therefore are not conditioned to think about the potential risk of discontinuing treatment in pregnancy. This also raises the question of whether discontinuation of therapy against guideline recommendations can be incorporated into the definition of clinical inertia, or whether this represents a distinct phenomenon.

The COM-B model and the TDF utilised in this study represented a systematic and comprehensive behavioural framework by which to assess both the individual and environmental influences on clinicians’ behaviour in this complex and under-reported reality. This allowed for a behavioural diagnosis of the potential drivers of clinical inertia. One of the key insights gained was around the low awareness of treatment guidelines for pregnant patients with CID. For some physicians, the lack of exposure to these patients means that they are unmotivated to invest the time to upskill themselves in the guidelines. In many hospital settings, a lack of active dissemination of guidelines places the responsibility on the clinicians to educate themselves. Even if a clinician does have sufficient knowledge of guideline recommendations, a lack of ability to explain risk to patients and/or a lack of experience doing this will impact the shared decision-making process. A feeling of a lack of support or unawareness of who to consult about guidelines may further impact their implementation. Social and cultural influences were also proposed to be factors affecting the dissemination and implementation of guidelines; however, the specifics of these were not reported by the authors and may warrant further exploration [29]. Since the studies investigated in this literature search predate the latest published guidelines of use of medications during pregnancy [49, 55], it would be of interest to investigate how the factors identified in this search reflects the current situation.

Fear about the consequences of teratogenicity is a strong affective component in the management of women of childbearing age, which likely stems from the experience with thalidomide and the more recent banning in the UK of valproate for women of childbearing age who are not enrolled in a pregnancy prevention programme [56]. The fear primarily sits with causing harm to the mother or baby, or both, however there also exist concerns about legal consequences and the high complexity of documentation in this context. Clinicians have to be very confident in their decisions in order to assure patients that a certain medication is compatible with pregnancy.

Another influence on the clinician’s pharmacological management of women with CID is the patient themselves and their concerns about the use of medications during pregnancy. This is in line with a shared decision-making approach recommended in many guidelines (for example the current EULAR guidelines for the treatment of RA [12]) where the patient’s perceptions of the risks associated with medication will also play a significant part in whether medication is discontinued or not. Outdated information about the safety of certain medications is a major issue in this context, represented by either incorrect information being provided to patients and clinicians from various sources, or based on historical and revised assumptions. An example of this is the inconsistent association between orofacial clefts and maternal use of corticosteroids despite this being disproven in numerous studies [57, 58]. Even with the appropriate knowledge and the motivation to prescribe a treatment, if clinicians fail to convince the patient that a certain medication is the optimal choice for them, then the opportunity to treat appropriately does not exist. Therefore, patient fears and concerns are likely to also impact clinical decision making.

The findings of this literature search suggest that clinicians managing women of childbearing age with CID could benefit from being made aware of clinical inertia as a concept, with interventions designed to educate and advise clinicians on how to recognise and overcome it. Clinicians could benefit from training on how to effectively communicate risk to patients – including the risk of active disease on their pregnancy along with the risks and benefits of the different treatment options available. Materials designed to aid this discussion (such as visuals aids) and that help patients clarify their individual preferences within the shared decision-making consultation could also be of benefit.

There is an increase in interest in the literature [7, 59‐61] as to why clinical guidelines in general are not adequately adopted [59]. However, given the level of perceived risk in managing pregnant patients, it is somewhat surprising that more research has not been conducted in how this affects clinical decision making. Given the results of this literature search, it would be interesting to conduct a cross-sectional behavioural study of clinicians to determine the extent to which heuristics and biases and other factors identified in the literature review influence guideline adoption and clinical decision making in the pharmacological management of women of childbearing age with CRD. This may also provide the opportunity to develop and validate tools with which to measure or grade heuristics and biases in this context.

The use of PubMed as the main search database, and the lack of inclusion of other databases such as Embase, represents a limitation of the current study. A further limitation of this study is that the risk of bias was not formally assessed in the papers selected for comprehensive analysis. This was due to the qualitative nature of the study, and the lack of randomised controlled trials investigating this specific topic which could have made a formal assessment of bias possible.

In conclusion, this literature search did not specifically identify any studies describing clinical inertia or heuristics/biases in the management of women of childbearing age with CID, nor did it elucidate if clinical inertia affects pregnancy outcomes – this in itself represents an unmet need in the literature. However, this search has identified that there are a number of factors that are likely to be influencing clinicians’ behaviour in this context, and therefore, it is likely that heuristics and biases are impacting the clinical decision-making process. These factors represent a starting-point for subsequent research investigating the specific attitudes and behaviours of clinicians in the management of women of childbearing age with CID.