It’s not (just) about the money

By Miriam WiersmaIan Kerridge and Wendy Lipworth

This post originally appeared in August 2018 edition of the Research Ethics Monthly and is reproduced with permission. It can be cited as Wiersma, M., Kerridge, I. and Lipworth, W. (22  August 2018) It’s not (just) about the money. Research Ethics Monthly. Retrieved from: https://ahrecs.com/research-integrity/its-not-just-about-the-money

Let’s imagine for a moment that you are a mid-career university researcher with growing expertise in a particular field. A pharmaceutical company contacts you and says that it would like to recognise the important work you are doing in this area, and has asked you to choose among the following forms of recognition:

Black and white image of a laboratory hallway, glass doors in the distance

Credit: Bill Dickinson

  1. $10,000 towards a research project related to one of the company’s drugs.
  2. Being chosen as a Keynote Speaker to present at a prestigious conference, with no honorarium.
  3. Being invited to join an international advisory board.

What would you choose? Would you choose the money? Or is there something appealing about the acknowledgement of your expertise in Option B, or impressive status associated with Option C?

Perhaps simply contemplating these questions makes you feel uncomfortable. After all, as medical researchers, questioning what motivates our behaviour or actions beyond the pursuit of scientific knowledge is not exactly pleasant. We like to think that we act in a way that is free from bias – and that while other researchers may have conflicts of interest, we certainly do not. Or not at least conflicts of interest that matter. Which begs the question – what types of things create conflicts of interest (COI)? Is it only when money enters the equation, or are there other forces at play?

It would appear, from the emphasis placed on financial COIs by medical journals, conference organisers and professional societies, that only money matters (Komesaroff et al. (2012)JAMA (2017). The COI disclosure forms that we dutifully complete tend to focus on financial COI and are comparatively vague when it comes to the declaration of non-financial COI (if indeed such declaration is required at all). Similarly, the disclosure statements made by speakers at conferences tend to take the form of ‘Dr X received $$$ from Company Y, $$ from Company Z’ and on the list goes.

But we believe that this exclusive emphasis on money overlooks many other non-financial interests that can create significant COI. These may stem from personal or religious beliefs – for example, Christian views about the moral status of the embryo held by legislators and scientists undoubtedly played a major role in the securing the prohibition of public funding of embryonic stem cell research.

Non-financial COI may also arise from a researcher’s desire for status or respect. As the case study illustrates, pharmaceutical companies may utilise both financial and non-financial incentives to encourage industry collaboration and promote industry agendas.

Personal circumstances and relationships also have the potential to give rise to non-financial COI – for example, if a member of a drug regulatory agency had a close relative who could benefit from the subsidisation of a drug under consideration this would constitute an obvious non-financial COI. Interests such as these have long been recognised in other contexts, including in the public sector (Australian Public Service Commission (2017)OECD (2003)). The OECD Managing conflicts of interest in the public service guidelines state that any ‘forward looking’ policy should describe non-financial sources of COI – including non-financial personal interests and relationships (OECD). The Australian Public Service Commission also specifies that social relationships and personal interests should be declared by employees.

We argue that to overlook non-financial COIs is problematic for several reasons (Wiersma et al. (2018a)Wiersma et al. (2018b). Most importantly, disregarding non-financial COI ignores the fact that serious harm may arise from such conflicts. We need look no further than the notorious Tuskegee scandal (Toy (2017) or Guatemalan ‘research’ (Subramanian (2017) to see that the drive to satisfy scientific curiosity can not only cloud researchers’ judgement, but can also cause significant harm to (unwilling or unknowing) participants.

Furthermore, ignoring non-financial COI also fails to take into account the fact that financial and non-financial COI are frequently entwined. For example, recognition by the pharmaceutical industry as a ‘Key Opinion Leader’ is not only associated with financial remuneration (for example, speaker’s fees), but also status and prestige.

We have also argued that non-financial COI can be managed using similar strategies to those used to manage financial COI (Wiersma et al. (2018a) There is no reason, for example, that a person on a drug regulatory committee could not disclose that they have a relative with a medical condition that may benefit from the drug under consideration and recuse themselves from voting in relation to that particular drug.

Of course, given the highly personal nature of some non-financial interests, it is important that declaration should only be required when evidence indicates that these may lead to a non-financial COI. Here we can draw from the Australian Public Service Commission guidelines which state that a personal interest does not lead to a conflict of interest unless there is ‘real or sensible’ (not merely theoretical) possibility of conflict. It is also crucial that declarations are handled with discretion.

None of this is to disregard the difficulties in determining what precisely constitutes a conflict of interest in medicine and how these should be managed. Medical researchers and practitioners have long grappled with these questions, and heated debate as to what should or should not be considered a ‘COI’ and what types of COI should be managed continues to this day (Bero 2017, Wiersma et al. (2018b).

However, we believe that acknowledging the importance of non-financial COI may be the starting point for a more sophisticated approach to managing both financial and non-financial COI in health and biomedicine. Perhaps most importantly, by acknowledging that we are all conflicted in certain ways, and that having a COI is not necessarily ‘bad,’ we may be able to take some of the ‘sting’ out of the label. And this may, in turn, encourage open discussion and disclosure of both financial and non-financial COI, enhance our understanding of COIs in general, and help us develop and refine a more nuanced approach to all forms of COI.

References

Australian Public Service Commission (2017) Values and code of conduct in practice.Australian Government. Available from: https://www.apsc.gov.au/aps-values-and-code-conduct-practice

Bero, L. (2017) Addressing bias and conflict of interest among biomedical researchers. JAMA: The Journal of the American Medical Association, 317(17): 1723-4.

JAMA: The Journal of the American Medical Association (2017) Conflict of interest theme issue. JAMA: The Journal of the American Medical Association, 317 (17):1707-1812. Available from: https://jamanetwork.com/journals/jama/issue/317/17

Komesaroff, P., Kerridge, I. & Lipworth, W. (2012) Don’t show me the money: the dangers of non-financial conflicts. The Conversation. March 30. Available from: https://theconversation.com/dont-show-me-the-money-the-dangers-of-non-financial-conflicts-5013

OECD (2003) Managing conflict of interest in the public service. OECD guidelines and country experiences. Organisation for Economic Co-operation and Development. Available from: http://www.oecd.org/governance/ethics/48994419.pdf

Subramanian, S. (2017) Worse than Tuskegee. Slate26. Available from: http://www.slate.com/articles/health_and_science/cover_story/2017/02/guatemala_syphilis_experiments_worse_than_tuskegee.html

Toy, S. (2017) 45 years ago, the nation learned about the Tuskegee Syphilis Study. Its repercussions are still felt today. USA Today. Available from: https://www.usatoday.com/story/news/2017/07/25/tuskegee-syphilis-study-its-repercussions-still-felt-today/506507001/

Wiersma, M., Kerridge I. & Lipworth, W. (2018a) Dangers of neglecting non-financial conflicts of interest in health and medicine. Journal of Medical Ethics, 44: 319-322. Available from: https://jme.bmj.com/content/44/5/319

Wiersma, M., Kerridge I. Lipworth, W. & Rodwin, M. (2018b) Should we try and manage non-financial interests? British Medical Journal, 361: k1240. Available from: https://www.bmj.com/content/361/bmj.k1240

Conflicts of interest: All authors had financial support from the National Health & Medical Research Council (NHMRC, grant number APP1059732) for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Miriam Wiersma is a PhD candidate at Sydney Health Ethics, University of Sydney, studying biomedical innovation.

Ian Kerridge is Professor of Bioethics and Medicine at Sydney Health Ethics, University of Sydney, and a Haematologist/Bone Marrow Transplant Physician at Royal North Shore Hospital.

Associate Professor Wendy Lipworth is a bioethicst and health social scientist at Sydney Health Ethics, University of Sydney.

Image by Bill Dickinson and used under Creative Commons 2.0

 

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Propaganda or cost of innovation? The high price of new drugs

Propaganda or cost of innovation? The high price of new drugs

Narcyz Ghinea, University of Sydney; Ian Kerridge, University of Sydney, and Wendy Lipworth, University of Sydney

Ever wonder how much it costs to develop a new drug? The independent, non-profit research group, The Tufts Center for the Study of Drug Development, estimates US$2.6 billion, almost double the centre’s previous estimate a decade ago. But how accurate is this figure?

While the details of the study remain a secret, a press release, slideshow and background document on the Tufts website provide some insight into how this figure was calculated. Interestingly, only slightly more than half of this cost is directly related to research and development (R&D). US$1.2 billion are “time costs” – returns that investors might have made if their money wasn’t tied up in developing a particular drug.

As expected, these costings have attracted the attention of policymakers, consumer advocates and critics of big pharma. In the New England Journal of Medicine, Harvard University Professor of Medicine Jerry Avorn questions several assumptions underpinning the Tufts costing – particularly the unverifiable claim that up to 80% of compounds are abandoned at some point during development.

Avorn is also unconvinced by the Tufts assertion that an annual return on capital of 10.5% (which was used to calculate the “time costs” component) is needed to attract investors, noting that “bonds issued by drug companies often pay only 1 to 5%”.

More broadly, Avorn questions the Tufts claim that its US$2.6 billion figure related to only “self-originated” products and wonders whether this includes contributions from the public purse for underlying basic science. If the Tufts figure didn’t include public contributions to research, the real cost of drug development would be even higher.

Finally, Avorn notes that pharmaceutical companies could fund much of their research themselves with the hundreds of billions of their own (untaxed) capital held outside of the United States.

Avorn’s criticisms echo those of the Union for Affordable Cancer, which complains that the study’s figures are already being used as a propaganda tool to justify high drug prices, particularly for cancer.

Like Avorn, the Union suggests that the Tufts figures also ignore the significant public contribution to drug development, particularly for cancer.

Others have argued the Tufts figure is grossly over-inflated. Rohit Malpani, director of policy and analysis at Doctors without Borders notes drugs can be developed for as little as US$50 million, and at most, for US$186 million when failures are taken into account.

Even Industry heavyweights such as GlaxoSmithKline’s CEO Andrew Witty have undermined the Tufts claims by suggesting in 2013 that the US$1 billion dollar figure was a myth.

So why is this debate important and why does it matter whether or not these estimate are correct?

These costs are used to justify high drug prices. These prices increasingly have the potential to disable health-care systems, create enormous opportunity costs (as funds that could be spent on other goods and services are diverted to purchase more and more expensive drugs), and place medicines out of reach of all but the most wealthy individuals or governments.

This is a reminder that the real issue is not how much it costs to develop a drug, but whether or not these drugs are worth the high prices pharmaceutical companies charge for them.

While advocates of a completely free market might see “just” pricing and all forms of price control as “medieval”, “socialist” or as suppressing innovation, others worry that drug prices bear little, if any, correlation with actual clinical value.

Rewarding innovation is necessary, but allowing drugs to be priced according to whatever the market will bear, rather than according to their benefits and cost-effectiveness, leads to inefficiencies, inequities and dramatic global inconsistencies.

Knowing how much it really costs to develop a drug might make it easier to negotiate drug prices on a global level and make revenues more predictable. This would not only be beneficial for society but could also ensure more predictable returns for the pharmaceutical industry.

At the moment, however, the industry seems entrenched in free-market thinking and has so far countered efforts by US lawmakers to shine a light on how much drug development really costs. While secrecy of this type may benefit industry, at least in the short term, this is simply not in the public interest.

Until we know more about the actual cost of drug development, we are in no position to meaningfully critique the corporate model promulgated by the pharmaceutical industry, the drug costs put before regulators, or the claims of groups such as Tufts. Ultimately, that leaves health systems at the mercy of industry.

The Conversation

Narcyz Ghinea is Postdoctoral Research Associate, Centre for Values, Ethics and the Law in Medicine at University of Sydney.
Ian Kerridge is Associate Professor in Bioethics & Director, Centre for Values and Ethics and the Law in Medicine at University of Sydney.
Wendy Lipworth is Senior Research Fellow, Bioethics at University of Sydney.

This article was originally published on The Conversation.
Read the original article.