On a rainy February day, I received an e-mail from my university about the St Gallen Wings of Excellence Award. This award, gave you the opportunity to win an all expenses paid trip to the St Gallen Symposium and all you had to do was write an essay on the theme of Breaking the Status Quo: Your Disruptive Idea. At the time, I did not expect anything to come of it, but eventually I discovered that I had been invited to work on my idea at the symposium with two teams of exciting and influential young people.
Upon my return to the UK, I began looking further into how to take this forward and Yekize was born. The foundation and it’s website are still in their early stages. We are awaiting funding and learning as much as we can so we can begin our research programme and then start delivering treatment. We have a long way to go, but we’ll get there. In light of this, I thought I’d share with you the essay that started it all…
Breaking the Status Quo: Incorporating Conditioned Placebo Response into Treatment Plans to Improve Access to Medicine in Least Developed Countries.
Access to treatment is one of the biggest challenges facing global medicine today. In least developed countries (LDCs), many patients are left with the choice of paying the high-price of private-sector medications or forgoing treatment (World Health Organization (WHO), 2010). But as many poorer patients do not have the money for expensive private medications, their access to treatment is dependent upon the thinly-spread public healthcare system – if there actually is one in their country (WHO, 2010). Governments and ‘big-pharma’ are often blamed for the lack of access to affordable medication in LDCs. And various initiatives have been tried to confront this angle, although relatively little impact has been made so far (Anon., 2014). But, what if there is a simple and novel solution to this problem? Recent research has shown that placebo responses of equal efficacy to active drugs can be obtained, and temporarily sustained, following a brief period of conditioning (Benedetti, 2016). If this was integrated into treatment plans, it has the potential to significantly reduce the demand for drugs and to vastly improve access to treatment in developing countries. Whilst there are obviously many ethical considerations, further exploration of the potential benefits should be made in an effort to improve treatment access in LDCs.
In this essay, I shall first discuss the scale of the access to medicine problem and why current initiatives have not worked. I will then outline the basic principles of conditioned placebo response and describe how it could be developed for application in global medicine. Next I will discuss the ethical implications and how we can tackle these issues with stringent testing. Finally, I shall amalgamate all these elements to demonstrate the potential of this approach to upgrade access to medicine.
The Scale of the Problem
According to the WHO (2016), the mean life expectancy of developed countries is 80.9 years, in great contrast to that of LDCs of just 63.4 years – 17.5 years less. Much of this disparity extends from access to medicine. Médecins Sans Frontières (MSF) estimate that one third of the world’s population do not have access to essential medication increasing to 50% of the population in the LDCs of Africa and Asia (MSF, 2014). MSF and various other organisations have had significant impact upon access to medicine in LDCs, by directing medical research towards LDC relevant drugs and by taking action to protect against corporate interests. Now, pharmaceutical companies have tiered pricing structures for LDCs and donation schemes have been set up (Anon., 2014). In addition, the Doha Agreement gave LDCs the right to purchase manufacturing licenses to produce generic forms of vital drugs. But these interventions, have not got near to solving the problem. The biggest disappointment was the Doha Agreement which may have been successful if more LDCs had pharmaceutical manufacturing facilities and if public healthcare was more of a priority to some LDC governments (Bosely, 2003). Therefore access to medicine is a continuing problem in need of a novel solution. So far, most approaches have not been adequately scaleable, or depend heavily on government and pharmaceutical cooperation. The introduction of conditioned placebo response into treatment plans is a more independent approach, requiring primarily just the cooperation of medical professionals and patients to improve treatment access in LDCs. Helping the same amount of drugs, to go further.
Conditioned Placebo Response and its Application to Global Medicine
Benedetti is arguably the world expert on mechanisms of the placebo effect, with very few other people conducting research in the field. His recent paper ‘Teaching neurons to respond to placebos’ (2016) is just the latest of a vast body of work that seeks to define the exact mechanisms behind the placebo effect. His recent paper looked at patients with Parkinson’s disease, measuring their placebo response after various periods of conditioning. He found that receiving four injections of the active drug over four days, adequately conditioned patients to respond clinically and neuronally to a single placebo, as if it were the active drug. It was found that this effect lasted for over 24 hours, and with the administration of another placebo, it continued for another 24 hours. The study did not assess the duration of effects beyond 48 hours, but if the conditioned placebo response is limited to 48 hours, it still has great potential.
Further tests need to be done, to understand if a greater period of conditioning would lead to a more sustained placebo response. And whether alternating the conditioning and placebo periods over time leads to renewed effects. If this is the case, then active drugs could be given to patients for four days, with a two day placebo period, alleviating the pressure on drug supplies, by reducing their need. To best apply this to global medicine, it will also be necessary to explore this with patients with a range of other diseases, to see if it would continue to be applicable to diseases more common in LDCs.
Resolving Ethical Conflicts
As stated previously, there are several ethical considerations that would need to be resolved in order to introduce conditioned placebo response to treatment plans. These issues involve ensuring efficacy, ensuring just evaluation of treatment (WHO, 2015) and quantifying the benefit/loss ratio. Our most natural response to the possibility of giving placebo conditioning to LDCs is that we immediately feel it is immoral to do so. Jumping to concern for exploiting LDCs and introducing deception into global medicine. We feel that our developed countries should value people of LDCs equally and not provide them with any treatment less than what we would use ourselves. However, whilst these perspectives are certainly valid, they may not actually be relevant concerns.
Firstly, on the point of deception, various studies have shown that patients can be told that they are taking a placebo and that they will still experience response (Blease, 2016). This is particularly true of conditioned placebo response as it does not appear to require conscious anticipation to work. This has been demonstrated by several studies involving mice who receive medication in saccharine sweetened water. After the medication is removed, they continue to respond to the saccharine flavour as if it were the active medication (Ader, 1975). Therefore, deception does not necessarily need to be involved, although the best options still need to be tested regarding this and the efficacy of placebo in global medicine.
Currently research into the incorporation of placebo response into Primary Care in more economically developed countries is being undertaken at various locations in the UK (Southampton, Nottingham, Oxford). Therefore, exploring the incorporation of placebo into treatments in LDCs would not necessarily demonstrate that we might value their lives as less than our own. We do deem placebos an adequate tool to explore for our own treatment, so therefore if we hold similar standards for LDCs we should be able to explore the possibility of placebo treatments in global medicine too. However, it is important to consider that diseases common in LDCs are not as common in our own countries, and if we were to suffer from them similarly, we may not deem placebo treatments adequate. Therefore, we must ensure that the risks, benefits and cost is calculated as it would be in our own countries. In the UK, before a treatment is made available on the NHS, the treatment is evaluated against the current treatments available, the risks and benefits of the treatment to the patient and the financial cost (Parliamentary Office of Science & Technology, 2015). Whilst, putting financial value on human life or quality life is understandably uncomfortable, it is a necessary measure that is done around the world. As there is no ‘Global Health Service’, and such measures are controlled largely at a national level, the evaluation must be done in light of the situation within the countries the treatment is proposed for. So, when evaluating the placebo treatment against the current treatment available, it must be considered that for many people, there simply may not be any treatment available. For many, it could be placebo treatment or no treatment. The cost and associated risks of placebos are negligible as there are no active ingredients. Therefore, considering the treatment evaluation methods in more developed countries, providing that placebo treatments are more effective than no treatment, and that they do not harm the patient, they should be considered for use in global medicine where treatment access in particularly poor.
Clearly, much research would need to be undertaken to clarify the efficacy of the placebo-integrated treatments and how they could be employed for the benefit of global health. However, given the potential benefits of incorporating conditioning in treatments plans, in global medicine, it is an area that should certainly be explored. Where there is little or no access to medicine, anything that could improve quality or length of life should be an area to be explored. If these methods can be used to reduce the demand for active medication in LDCs there is the potential, that many more people could receive treatments, not just those who can afford it.
Anon. (2014) Editorial: Access to medicines is a global struggle. The Pharmaceutical Journal 293:7830. Available at: http://www.pharmaceutical-journal.com/opinion/editorial/access-to-medicines-is-a-global-struggle/20066682.article
Ader R, Cohen N (1975) Behaviorally conditioned immunosuppression. Psychosomatic Medicine 37(4):333-40. Available at: https://www.ncbi.nlm.nih.gov/pubmed/1162023
Benedetti F, Frisaldi E, Carliono E, Giudetti L, Pampallona A, Zibetti M, Lanotte M, Lopiano L (2016) Teaching Neurons to Respond to Placebos. The Journal of Physiology. 594(19):5647-5660 Available at: http://onlinelibrary.wiley.com/doi/10.1113/JP271322/full
Blease C, Colloca L, Kaptchuk TJ (2016) Are open-Label Placebos Ethical: Informed Consent and Ethical Equivocations. Bioethics 30(6):407-414. Available at: http://onlinelibrary.wiley.com/doi/10.1111/bioe.12245/abstract
Bosely S (2003) Dying for Profit. The Guardian. Available at: https://www.theguardian.com/environment/2003/sep/08/wto.fairtrade7
Médecins Sans Frontières (2014) Access to Medicines. Médecins Sans Frontières. Available at: http://www.doctorswithoutborders.org/issue/access-medicines.
Parliamentary Office of Science & Technology (2015) Value Based Assessment of Drugs. PostNote. Available at: https://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=5&ved=0ahUKEwiKjuq1w-zRAhUpIsAKHWHKDR8QFggyMAQ&url=http%3A%2F%2Fresearchbriefings.files.parliament.uk%2Fdocuments%2FPOST-PN-487%2FPOST-PN-487.pdf&usg=AFQjCNFYhT0C-h-ciPH16v2BPIYLaa3yow&sig2=8QHqgFrwEf2rFqt12lhfgA&bvm=bv.145822982,d.ZGg
World Health Organization (2010) Access to Affordable Essential Medicines. World Health Organization. Available at: http://www.who.int/medicines/mdg/MDG08ChapterEMedsEn.pdf .
World Health Organization (2015) Global Health Ethics: Key Issues. World Health Organization. Available at: http://apps.who.int/iris/bitstream/10665/164576/1/9789240694033_eng.pdf
World Health Organization (2016) World Health Statistics 2016: Monitoring health for the SDGs Annex B: tables of health statistics by country, WHO region and globally. World Health Organization. Available at: http://www.who.int/gho/publications/world_health_statistics/2016/Annex_B/en/
Works Consulted but not Cited
Ahmanadiani S, Nikfar S (2016) Challenges of access to medicine and the responsibility of pharmaceutical companies: a legal perspective. DARU (Journal of Pharmaceutical Sciences) 24:13 Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855755/
Benedetti F (2012) Placebo Effects: Understanding the mechanisms in health and disease. Oxford University Press, UK.
Iserson KV, Biros MH, James Holliman C (2012) Challenges in international medicine: ethical dilemmas, unanticipated consequences, and accepting limitations. Academic Emergency Medicine 19(6):683-692. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22548491
Mercurio, B (2007) Resolving the Public Health Crisis in the Developing World: Problems and Barriers of Access to Essential Medicines. Northwestern Journal of Human Rights 5(1):1-40 Available at: http://scholarlycommons.law.northwestern.edu/cgi/viewcontent.cgi?article=1046&context=njihr
World Health Organization (2010) Access to Essential Medicines. World Health Organization. Available at: http://www.who.int/healthinfo/systems/WHO_MBHSS_2010_section4_web.pdf