Patients and carers views must be involved in the rollout of precision medicine

December 2020

The sequencing of the human genome has begun to enhance our understanding of the biological mechanisms underlying chronic diseases, for example asthma. The twentieth century model of asthma management is often that of a generic disease with grades of severity, treated by adding layer on layer of medicine. However, the discoveries that follow from the description of the human genome are influencing our thinking. They are enriching the established milieu with additional information about new individual pathways, urging us to move “from mostly one-size-fits-all treatment to genuinely personalized care.” [1] We may soon have the power to decide whether or not we can let this novel information fine-tune the management of chronic diseases in wider populations.

Or will we? We are only empowered by information when we understand and realise it. Currently, there exists a gap between the information about genomics and chronic diseases that researchers know and share through articles in specialist journals, and the understanding of this information among patients and carers, the public, and many healthcare professionals. Unless this gap closes, doctors, nurses, patients and the public cannot make the right decisions about future patient care, and a small body of experts, with or without links to industry, may remain in the driving seat through sheer knowledge power, and this might not work in the best interests of the patients.

A recent systematic review of 21 studies demonstrates an overall interest in 9000 members of the public, including patients, almost exclusively from North America and Europe, to engage in a wider discussion on personalised medicine. [2] However, other than one study from Singapore, we could identify no evidence of a systematic exploration of the public’s views on personalised medicine from Africa, South America and Asia, where over half the world’s populations live, and where personalised medicine-related treatment approaches will inevitably influence the management of common diseases over the next decade.

Historically, doctors may not have been efficient at seeking patient’s views about new treatment choices, but views are shifting in the North, and we were pleased to note the breadth of studies seeking the views of the public regarding personalised medicine. Many of us in the developed world are actively seeking patient feedback regarding our day-to-day performance, while researchers are exploring opportunities for public engagement to discuss future medicine and inviting public involvement to strengthen clinical trial design.

How much of this is happening outside the developed world? The treatment choices are creeping in, often at different rates, depending on ability to pay. From the patient’s point of view, there is arguably an even greater need to think about cost versus benefit. Our exploratory discussions last year with rural and urban populations in India revealed one clear message: people, particularly the young, are keen to engage in this process, but there is very little scope for discussion. Young women employed in rice fields spared their valuable morning time learning how a skin barrier defect might worsen their child’s asthma or eczema and joined in the discussion on how this could be prevented through the use of emollients that are available in the local market. [3,4] Speaking in the local language (Bengali) and translating from English as necessary, we used models and pictures, communicating allergy advice. As doctors and researchers, we learnt that there are fewer cultural, educational and economic barriers to worldwide public participation in discussing the pros and cons of medical treatments than we currently perceive.

We know that the price of ignoring the views of patients and carers is high. We run the risk of mis-diagnosis, overdiagnosis and overtreatment, or in ignoring the public’s views when developing research programmes. In Europe, a clear and articulate patient voice is guiding the development of these interventions. There are, however, major healthcare and societal costs if patients and carers are not involved worldwide in the roll out of personalised medicine over the forthcoming years.

Somnath Mukhopadhyay is Chair of Paediatrics at the Royal Alexandra Children’s Hospital and the Brighton and Sussex Medical School, UK. He is a consultant in children’s respiratory diseases and allergy. 

Katy Fidler is Clinical Senior Lecturer in Paediatrics at the Royal Alexandra Children’s Hospital and Brighton and Sussex Medical School, UK. She is a consultant in children’s infectious diseases.

Ciara Holden is a clinical academic fellow and specialist registrar in paediatrics at the Royal Alexandra Children’s Hospital in Brighton, UK. 

Christina Jones is a senior lecturer in Clinical Psychology at the University of Surrey, UK.

 

 

Every child is different

My jokes are usually quite poor and sometimes I can tell the student is laughing so as not to embarrass their ageing professor. Still, at the start of my blog, I will share one with you. When we have seen a few children at our clinic, I would often turn towards the medical student and say, “If you do believe God or some other entity had a role in creating humans, you have to agree that he had no understanding of our specialist registrar training programmes. Otherwise, how could he create a single disease that can require the involvement of so many different services:  respiratory, ENT, dermatology, dietetics, allergy, gastroenterology, clinical psychology? Unless he was acting with clear malicious intention, and you wouldn’t of course expect such intention of God?”

The medical student usually smiles obligingly, but I sometimes do feel I might have got the student to ponder over this for a moment or two (“What on earth is he trying to say?”).

The condition I manage in my clinic affects children from very early life and can cause a lot of suffering through childhood and, to a varying extent, into adulthood. It can start off as, or progress to, vomiting and difficulty in digesting food in early infancy, crying during infancy, bouts of rashes and inflamed skin, fully-developed eczema, food allergies, life-threatening allergic reactions, varying levels of recurrent wheeze leading to a diagnosis of asthma, nasal obstruction with snoring and, sometimes, breathing pauses during sleep that could in rare instances affect the brain. Anxiety, both intrinsic and generated by one or more of these conditions, often plays an important role. Eczema, asthma, food allergy or rhinitis, and other such individual diseases, are treated by specialists with expertise in the individual area in question. A child with two or three of these conditions, such as asthma, nasal disease, eczema and food allergy, often gets referred to two or three different clinics, and each doctor manages the part of the problem that is aligned to his or her own interest. Thus the ENT doctor manages the nasal blockage and snoring, the dermatologist treats the eczema, the respiratory specialist the wheeze, while the dietician or gastroenterologist may focus on the recurrent reflux, abdominal discomfort or loose and smelly stools.

Finding the right healer

This could mean that the child and family experience fragmented care, visiting one doctor or nurse after another and often receiving conflicting advice and management plans. In health care systems with long waiting lists, it could mean that care directed to individual body systems, such as skin, upper or lower airways or gut, happens at different points in time over a period of a year or longer. One possible solution to this problem could be through the development of joint clinics attended by ENT surgeons, dieticians, respiratory specialists, dermatologists and so on. This is expensive, as the cost of running a single clinic and the cost of seeing one child in the clinic is much higher if 3 or 4 professionals are involved, rather than for a single professional. An individual clinician in such a joint clinic may also not be “fully utilised” for each consultation, as some children may have involvement of a single system only, such as the skin or the lower or upper airway. An alternative approach could be to develop, for a group of health professionals, an overall understanding of the processes leading to disease in each of the organ systems, through providing generic training in all the different areas, in order to equip them with skills to help the child and family from all these different perspectives. Such an approach could improve care for a very common childhood condition that affects at least a fifth of children at some stage in their lives.

Finding the right treatment

However difficult this is, finding the right healer is not enough. Current research shows that every child is different, thus individual children with conditions like allergy, eczema or asthma have their individual set of problems. Generic treatment with medicine manages the outward manifestations but does not address the underlying problem. For example, a defect in a skin barrier protein could make a newborn infant more vulnerable to allergic sensitisation to cat dander, which leads the child to have eczema, nasal disease and wheeze in early life, then asthma and nasal problems through childhood. We are currently treating such children with steroid creams for her eczema, subsequently, inhaled steroids for the asthma, and so on. However, if the primary defect was identified early, the child might benefit from early interventions, such as better barrier protection, reduced exposure to cat dander, and thus not suffer from the progressive development of health problems affecting different systems, and perhaps also receive less steroid and other medication through life. We know that a proportion of children with particular genetic traits are more vulnerable to asthma attacks and to anaphylactic reactions from peanut sensitisation. Tracking the development of peanut sensitisation in these vulnerable children may help prevent life-threatening anaphylactic reactions and asthma attacks. Some children with asthma with identifiable genetic traits may not respond to certain common asthma medications. For example, studies in the UK and the Netherlands in children with asthma have shown that those carrying a particular genetic abnormality have a poor response to particular groups of medicines (salbutamol, salmeterol or inhaled steroids) whereas children who do not carry this trait respond much better to these medicines. Identifying these children and prescribing alternative medicines for these children could improve their quality-of-life and reduce their risk of asthma attacks. Helping anxious children and families develop greater insight could improve their asthma and reduce their medication needs.

The main point underlying this proposed approach is that management requires to be ‘personalised’ for each individual child and family. This is in contrast to the ‘one-size-fits-all’ approach where every child follows the same management protocol. This is a good time to discuss the two approaches because recent research in asthma and allergy is pointing towards individual strands where particular management approaches could be more beneficial in particular patients. For maximum benefit, such ‘personalisation’ should perhaps happen right from the beginning of life or, at least, from a very early point in the appearance of this cluster of conditions. The child who is vulnerable to some of these conditions will probably benefit most from being identified at birth and exposures that are known to be particularly harmful to this child could perhaps be reduced from an early stage. If disease develops, genetic testing could identify the medicines the child will most benefit from, and could select out the medicines to which the child is likely to show a poor response.

So, why am I writing this blog?

The purpose of writing this blog is to start a discussion around this possible shift in approach in the management of children with these conditions. We hope carers of children with asthma, the children themselves, health professionals and the general public might be interested in joining in this debate. Is our current manner of treating these conditions pretty effective and should we stick to our current strategies for treatment? Are we already taking a personalised approach and is there perhaps no need for any further development of precision approaches within our practice? What are the potential pitfalls?

Prof Somnath Mukhopadhyay, Foundation Chair in Paediatrics, Royal Alexandra Children’s Hospital, Brighton and Sussex Medical School.

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