One size drug does not fit all: genetics and non-adherence

Adherence to treatment balances on patients’ beliefs about the necessity for medication and their concerns about taking it (Necessity-Concerns Framework, NCF™). To support patients effectively there is a need to personalise. Each person’s experience of a medicine is particular to them and this experience is a key part of how they view that medicine. As the technical aspects of medicines continue to develop, this experience does not need to be left entirely to a ‘suck it and see’ approach. Let us take an example from genetics.

Variability in patients’ genetic characteristics can affect how patients respond to treatment. This variability can come in terms of enhancing their tolerance or resistance to a medicine, or altering their susceptibility to side effects. Genetic variation can, therefore, change behaviour towards medication especially when a patient’s perceived necessity and concerns deviate from the expected when they are given a standard dose. This jeopardises the patient’s motivation to take the medication as prescribed.

Control trials may not account for genetic differences in their participants’ selection process, usually recommending a one-size-fit-all type of dose [1]. Prescribing the same dose to all patients puts these patients at risk of non-adherence. If the patient experiences more side effects than somebody else on the same dose (concerns), or if the dose does not work (necessity). These change the perceptions a patient originally has about a medication.

For example:

CYP2C9 is an enzyme that metabolises warfarin to clear it from the body; since people with genetic polymorphisms of CYP2C9 are at double the risk of bleeding [2], this subgroup of patients, as they experience bleeding, will have increased concerns about their medication.

Genetic variability modifies the neurotransmission pathways, which affect the perception and sensitivity to pain (e.g. for migraine and cancer patients) [3]. This reminds us that treatment responses to analgesics will be patient-dependent and patients will need different amounts of medication for a given pain, potentially increasing side effects, lowering perceived efficacy and, in turn, the patient’s concerns towards their medication. In these cases, precision prescribing, by tailoring the dosage to a specific patient, may result in better adherence.

Pharmacogenetic testing may support medication adherence by increasing the patients’ understanding and confidence about their treatment. Studies have suggested that knowing you are being tested reduces anxiety about the treatments’ consequences, while discussing genetics with patients can increase patient-clinician communications and create a sense of control for patients who then share decisions with their doctor [4], positively contributing to adherence.

Currently, studies associating pharmacogenetics with health outcomes are scarce. Adherence programmes for therapy areas where it has been demonstrated genetic differences matter need to include tailoring the interventions to effectively support patients with these genetic polymorphisms.

[1] Frueh FW. Back to the future: why randomized controlled trials cannot be the answer to pharmacogenomics and personalized medicine. Pharmacogenomics. 2009;10:1077-1081. [2] Sanderson S, Emery J, Higgins J. 2005. CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: A HuGEnet™ systematic review and meta-analysis. Genet Med. 2005;7:97-104. [3] Zorina-Lichtenwalter K,

Meloto C.B., Khoury S., Diatchenko L. Genetic predictors of human chronic pain conditions. Neuroscience. 2016; 338:36-62. [4] Haga SB, La Pointe NMA. The potential impact of pharmacogenetic testing on medication adherence. Pharmacogenomics J. 2013;13:481–483.

Understanding treatment-related behaviour

The extended common-sense model of self-regulation (eCSM) provides a framework by which we can work to gain valuable insights from patients to understand how their illness perceptions and beliefs about medicines impact their treatment-related behaviours. These can be addressed by using behavioural science principles to effectively improve adherence and optimise patient outcomes.

The common-sense model of self-regulation (CSM) is a dynamic framework which seeks to explain the processes by which beliefs about illness impact on behaviour. The CSM proposes that in response to a health threat, such as a medical diagnosis, people construct cognitive representations of their illness (illness perceptions) based on internal cues, such as symptoms, and external cues, such as information from a clinician. The CSM proposes that behaviours to cope with an illness are driven by illness perceptions. The coping behaviour is then evaluated and adapted based on its apparent success.

Studies applying the CSM in a range of health-related behaviours provided empirical evidence to support the role of illness perceptions as predictors of health-related behaviour, however, there is less support for the application of the CSM to treatment-specific behaviours. Studies applying the CSM to adherence to prescribed medication in chronic conditions found only weak associations between illness perceptions and adherence behaviour. This suggests illness perceptions alone are not the best, or only, predictors of treatment-related behaviour.

The ability of the CSM to explain treatment-related behaviour may be increased by taking patients’ beliefs about treatment into account. For example, decisions to initiate, persist and adhere to medication are better explained by both illness perceptions and beliefs about medications.

Beliefs about medications can be grouped into beliefs about medicines in general (such as the belief that doctors over-prescribe medications or that medicines can be harmful) and beliefs about specific, prescribed medications (beliefs about the necessity for treatment and concerns about the potential adverse effects of a medicine). People with negative beliefs about medicines in general are less likely to adhere to medication. Patients with doubts about the necessity for treatment, or strong concerns about adverse effects, are more likely to decline treatment or be non-adherent.

The eCSM includes specific and general beliefs about treatment to increase the ability of the CSM to explain treatment-related behaviours. According to the eCSM, adherence will depend on whether a person perceives their illness warrants treatment, based on their illness perceptions, and whether they believe they have been prescribed appropriate treatment, based on their general and specific beliefs about the treatment. Uptake, adherence and persistence to medication is likely to be influenced by patients’ beliefs about treatment, as well as their illness perceptions. We must therefore use behavioural science to target both illness perceptions and beliefs about treatment to optimise patient outcomes.

What does pain mean to the patient?

Pain is a person’s private and unique experience, and no one except that person can know what their pain feels like.

There is a real dynamic relationship between the emotional and physical conditions of an individual and their experience of pain.

Long term pain puts stress on the brain which is revealed cognitive issues such as low mood, difficulty with memory or concentration, no matter what the underlying condition causing pain is.

Chronic pain and its psychological effects reduce quality of life, not only for the person with pain but for their family as well. In some cases, the psychological effects of pain outlives the pain itself and become the major health disorder. For instance, under-managed chronic pain may lead to less sleep, exhaustion, more stress, relationship and work problems and psychological distress so it is important to be able to intervene in this cycle to improve pain management and psychological welfare.

Pain can prevent people engaging with care that would improve their outcomes, and for each person the support they need is as unique as their experience of their pain.

Personalisation is essential when creating effective support programs for the patients.