Expert Review: co-morbidities in an ageing population – the confounding factor that must not be ignored

Suzanne Wait

SHW Health Ltd.

This September, the UN hosted its first High-Level Summit on Non-Communicable Diseases (NCDs). The Summit marked two critical facts. First, NCDs, or chronic diseases, are no longer solely the concern of rich countries: they have superseded infectious diseases as the largest threat to public health in the developing world. This is due mostly to the ageing of the population. By 2040, over 1 billion people over 65 will reside in developing countries, accounting for 76% of the world’s total. Indeed, the most rapid increases in the number of people over 65 are expected in developing, as opposed to developed, countries in the next few decades. A telling illustration of this is the headline of a recent FT article which read ‘Africa struggles to control a prolific killer.’ The article was talking about diabetes. Twenty or even 10 years ago, it would have been talking about AIDS.

The second critical fact highlighted at the Summit was that chronic diseases should not be looked at in isolation, instead, strategies to prevent them and care pathways to minimise the burden they pose on our populations should be looked at jointly. This has long been the discourse of the WHO and other public health bodies. Nonetheless, seeing advocacy groups and experts representing the fields of cancer, cardiovascular disease, diabetes, and respiratory disease sit around a common table was quite remarkable, considering the fact that, on a day-to-day basis, these players are essentially competing for ever-limited donor funds and fickle political attention.

In actual fact, this co-habitation of the different NCDs mirrors what is happening within our ageing populations: as one ages, one’s risk of developing a chronic condition increases, as does the risk of suffering from several conditions at the same time. Of course this may also occur in younger patients as well: the typical patient of the future is unlikely to present with a single disease and instead, will have co-morbidities that must be taken into account when considering diagnosis, treatment pathways and expected outcomes.

“…the presence of co-morbidities challenges the way we plan, organise and deliver healthcare.”

Let’s take the specific example of diabetes and depression. Recent studies have suggested that between 18-26% of patients with Type 2 diabetes are affected by depressive disorders.1-3 The presence of depression is thought to exacerbate non-compliance to medication, it increases the risk of complications5,6 and leads to greater functional disability, lower quality of life and higher mortality in diabetic patients.7,8 Yet screening for depression is anything but common practice in diabetes clinics. In fact, experts in the fields of mental illness and diabetes have recently joined forces in calling for the modification of existing guidelines and professional training to ensure that they address the needs of patients living with both conditions simultaneously.

As the above example illustrates, the presence of co-morbidities challenges the way we plan, organise and deliver healthcare. Policymakers in Europe and elsewhere have called for the need to better integrate the delivery of care around the comprehensive needs of the individual and have tried to modify models of care to help individuals, particularly as they age, live with the demands and complications of different conditions. The terms of integrated care, person-centred care and multi-disciplinary care networks, have floated around health reform manifestos for decades. However in practice, such reforms remain, for the most part, essentially in pilot mode.

What does this all mean for the pharma industry? Unfortunately, industry reflects the system it operates within and remains very single-disease focused (if not single asset-focused). If one looks for example at clinical trials, their design is driven by the need to optimise internal validity of findings. Therefore, the trial population is kept as ‘pure’ as possible, and all confounding variables are kept to minimum. While this is completely justified for regulatory purposes, the result is that trial populations do not resemble the patient populations that drugs will eventually be prescribed to – or put differently, the external validity of trial data is poor.

“…trial populations do not resemble the patient populations that drugs will eventually be prescribed to…”

A recent publication looking at all clinical trials published on heart failure makes this strikingly apparent. The majority of patients treated for heart failure are over the age of 65. However, up to 25% of clinical trials in heart failure had a set upper age limit of 65 or more, 80% excluded patients with co-morbidities and 5% with polypharmacy.9 Similar rates have been reported in other disease areas as well.

The lack of representativeness of clinical trial populations has long been a bug bear of health economists and Market Access experts, as they strive to provide payers evidence of what the impact of given drugs is in the so-called ‘real world’. Already back in 1999, NICE (the National Institute for Health and Clinical Excellence in England) rejected Relenza on the grounds that the clinical trial data put forth by the sponsor at the time did not have sufficient evidence of benefit in older people, when the majority of patients who would be given Relenza were over 65. Today, this kind of criticism is increasingly echoed by payers around the world: present us with data that prove that your drug will work in the populations to whom they will be prescribed. In our ageing world, where within less than 20 years one can expect that over 20% of the population will be over 60, this means that evidence of benefit in older people and particularly, older people with co-morbidities, is no longer an option, it is absolutely critical.

But beyond the realm of clinical trials, there are a number of ways in which companies may shift their focus from a single-disease track to take on a more holistic perspective. It would be naive to suggest that companies should move away from a product- or brand-focus. However, somewhere ‘above brand level’, there is room for a cog in the organisational wheel that has as its remit to take a cross-sectional, across-brand, view of a company’s portfolio, overall positioning and business development opportunities. Some possible inroads may include:

• When evaluating unmet medical need for a given product or disease area, seek out epidemiological data that reflects the full spectrum of co-morbidities present within different target populations, so that important subgroups may be identified early on.

• Find synergies between brand-focused groups that often work in parallel. For example, encourage cross-brand discussions about generic issues to encourage cross-fertilisation of ideas and insights.

• Ensure that all personnel working directly with physicians (sales reps, medical science managers,…) have a good understanding of the patient population they are serving. What other drugs are patients taking and what are the start-stop rules that may need to be applied when co-administering with the new product? How does the drug fare in older patients and those with co-morbidities? These questions should be anticipated and answers included in all in-house training efforts.

“…present us with data that prove that your drug will work in the populations to whom they will be prescribed.”

• Anticipate questions from payers about the external validity of trial results and create opportunities for creating the evidence they ask for through observational studies and other research vehicles.

• Engage with primary care practitioners as well as specialist KOLs. They are likely to have a much broader (and more realistic) sense of the patient’s entire experience, as opposed to what happens within the artificial confines of a given condition.

• Seek partnerships with patient advocacy groups and listen to the experience of patients. Bring different partners around the table who would not usually speak to each other but who work in the same ‘space’ around the patient experience. Become a legitimate partner in this process, not just a supplier of a given drug.

Is this all pie in the sky? I believe not. Co-morbidities in an ageing patient population are a confounding factor that is not going to go away. Companies that are bold enough to make appropriate shifts in their strategies, organisation and mindset to adapt to this shift in their external environment are bound to be better off in the long run. Of course, there is no guarantee, and everything must start with a promising pipeline. But one would hope that those pharma companies that arm themselves with a better understanding of the populations they wish to serve will, ultimately, improve their chances of producing drugs that meet real unmet needs and thereby reaching as many patients as possible. And surely, this is a goal worth pursuing.

References:

1. Katon W et al. Diabetes and poor disease control: Is comorbid depression associated with poor medication adherence or lack of treatment intensification? Psychosom Medicine 2009, 71: 965.

2. Anderson RJ, Freedland KE, Clouse RE &amp, Lustman PJ. (2001). The prevalence of co-morbid depression in adults with diabetes. Diabetes Care, 6, 1069-1078.

3. Petrak F, Herpertz S. Treatment of depression in diabetes: an update. Curr Opin Psychiatry 2009, 22(2): 211-217.

4. IDF Diabetes Atlas, www.diabetesatlas.org/content/diabetes-and-depression

5. Rustad JK, Musselman DL, Nemeroff CB. The relationship of depression and diabetes: pathophysiological and treatment implications. Psychoneuroendocrinology 2011, ePrint accessed April 2011.

6. De Groot M, Anderson R, Freedman KE, et al. Association of depression and diabetes complications: a meta-analysis. Psychosom Med 2001, 63: 619-30.

7. Egede LE, Nietert PJ, Zheng D. Depression and all-cause and coronary heart disease mortality among adults with and without diabetes. Diabetes Care 2005, 28: 1339-45.

8. Le TK, Able SL, Lage MJ. Resource use among patients with diabetes, diabetic neuropathy, or diabetes with depression. Cost eff Resour Alloc 2006, 4: 18.

9. Cherubini A, et al. The persistent exclusion of older patients from ongoing clinical trials regarding heart failure. Arch Int Med 2011, 171(6): 550-6.

About the author:

This article was written by Suzanne Wait, Director of SHW Health Ltd, and was commissioned by PiR Limited. Suzanne is Director of SHW Health Ltd, a London-based consultancy which specialises in health policy and market access. The company works with clients from all sectors in health to help them better prepare for and address the needs of the external environment. For further information, please contact Suzanne at Suzanne@shwhealth.co.uk, or by mobile on +44 7740 070489.

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Is it time we paid more attention to co-morbidities in ageing patients?