Tamiflu

Why is Industry-funding an Issue?

Franklynn Bartol

Industry-funded medical research is a normalized part of pharmaceutical testing. Drug and medical device companies routinely carry out internal clinical trials to test their own products. Since the successful approval and marketing of their products directly relies on favourable trial outcomes, independent academic studies—with no financial interests in the results—should also test new drugs and medical products.

But clinical trials are incredibly expensive and often unaffordable for universities, so independent academics can’t always keep up with the amount of research coming from  industry itself. With increasingly insufficient government funding, even academics sometimes rely on industry grants to carry out medical research.

Many say that this rampant industry-funding leads to biased scientific outcomes, directly influencing medical opinions and practices in ways that support industry profit over public health. In a critique of industry-funded Tamiflu trials, Carl Heneghan, Director of the Center for Evidence-Based Medicine at the University of Oxford, notes the breadth of this problem:

“In 2014 in the Annals of Internal Medicine, 7 out of 8 studies involving researchers with financial conflicts of interest came to positive conclusions about the effectiveness of neuraminidase inhibitors. But, only 5 of the 29 studies conducted by scientists who did not receive money had favorable outcomes.” 


Tamiflu research is just one case in a general trend across clinical research. Multiple studies have shown that industry-funded clinical trials are more likely to provide pro-industry findings (Bandari et al., 2004; Lundh et al., 2012; Lundh et al., 2018; Sismondo, 2007).  Authors of a study can also have personal financial ties to the industry.

This was the case with Tamiflu when several authors of the WHO’s 2004 pandemic planning guidelines had also been contracted by pharmaceutical companies to promote the use of antivirals for influenza. 

It may seem like a given, but this is backed up by data: research shows that when study authors have such conflicts of interest, they are more likely to make industry-favourable conclusions about their research (Ahn et al, 2017; Cherla et al., 2019). 

These conflicts of interest also influence the academic and medical opinions offered to the public. One study analyzing media reports during the 2009 swine flu pandemic revealed that quoted academics promoting the use of antivirals were 8 times more likely to have industry links (study not publically available). 

How can this bias happen when, presumably, all research follows similar scientific practices? Part of the issue is ‘design bias’, where studies are designed in ways that increase the likelihood of favourable results.

For example, a trial could be done on a short timeline to reduce the likelihood of adverse effects coming to light, or the dose of a comparator drug could be altered so that the company’s drug looks better by comparison (Safer, 2004). 

But focusing solely on methodological choices implies a simple solution: more rigorous methodological protocols. Unfortunately, it’s more complicated. As scholar Sergio Sismondo, whose research investigates the nature and distribution of pharmaceutical research, notes:

“Because the bias is not the result of simple methodological problems, radical solutions are called for, that divorce the pharmaceutical industry from published research” (Sismondo, 2007). 

 

Which research gets published

One of the reasons that industry-funded research has more favourable outcomes is that pharmaceutical companies are selective with which trials they publish and what results they include. In this Ted Talk, Dr. Síle Lane from Sense about Science, an independent charity challenging misrepresentation of science and evidence, discusses evidence that half of all clinical trials on drugs are not published and outlines the serious consequences this has on public health. 

 

Lane gives the  harrowing example of the cardiovascular drug Lorcinide. Data about lethal side effects was withheld, leading to an estimated 100,000 patient deaths. Withholding trial data puts not only patients but also research participants at unnecessary risk, since non-industry researchers unaware of these findings must carry out trials to further test the drug.

Lane also discusses Tamiflu, highlighting that governments spent billions of dollars stockpiling the drug based on the published clinical trial results, which turned out to be a minority of the trials actually conducted by Roche, the pharmaceutical company making the drug.

Tom Jefferson is now suing Roche on behalf of the U.S. Government for the $1.5 billion it spent stockpiling Tamiflu based on the misrepresented trials. 

Who writes the research

One of the reasons it can be hard to catch potential bias in published articles is that industry-sponsored research often goes hand-in-hand with a lack of transparency about study authorship. Ghost authorship is the industry practice of hiring medical writing agencies to prepare papers that are then signed by academics who had little or nothing to do with the study.

Of course, the ghost writer’s name is not included in the final paper. This allows the industry to present their own research interpretations as independent scientific opinion 

Ghostwriting is common, but we usually only hear about it when a drug is revealed to be less effective or more harmful than the published literature suggests. In the case of Tamiflu, the ghost authorship of several Roche-funded clinical trials was revealed after increased scrutiny. 

One of the most extensive examples of ghostwriting made headlines in 2008 during lawsuits against pharmaceutical company Wyeth. More than 14,000 plaintiffs brought claims related to the development of breast cancer from their hormone therapy (HT) drug Prempro.

During that case, 1,500 documents were made publicly available through PLoS (Public Library of Science) Medicine. The documents detailed the company’s marketing plan to hire a medical writing agency to publish favourable articles in multiple prestigious journals.

In a published analysis of the documents, pharmacology researcher Adriane Fugh-Berman reveals how Wyeth used ghost-written reviews, posts, and 26 scientific papers “to mitigate the perceived risks of breast cancer associated with HT, to defend the unsupported cardiovascular “benefits” of HT, and to promote off-label, unproven uses of HT”.

Wyeth had contracted a medical communications company to write the articles and solicit influential physicians to add their names as authors, even though many had contributed little or nothing to the writing. 

For an in-depth look at the drug industry’s marketing practices, including ghostwriting, see Science and Technology scholar Sergio Sismondo’s book Ghost-Managed Medicine: Big Pharma's Invisible Hands

 

Which research gets funded

Reliance on industry funding has real-world consequences for which drugs are available and what medical science is pursued. Treatments that have little promise for high profitability are unlikely to receive enough funding for research and development. One 2018 study published in the American Journal of Public Health investigated whether industry-funding drives research agendas. Based on its findings, it concluded: 

“Corporate interests can drive research agendas away from questions that are the most relevant for public health….The influence on the research agenda has given the industry the potential to affect policy making by influencing the type of evidence that is available and the kinds of public health solutions considered. (Fabbri et al, 2018)

 

When diseases occur in sporadic outbreaks or in third-world countries, their treatments are considered unprofitable. Therefore, even if the science is available, these treatments remain under-developed and unavailable. CBC News highlighted this issue in their coverage of the Canadian-made Ebola vaccine. Experts say the vaccine could have prevented thousands of deaths if it had been funded for trials and development before the 2014 outbreak. 

Organizations like Drugs for Neglected Diseases are attempting to fill this gap by providing non-profit drug research and development for diseases overlooked by pharma companies. However, they lack the financial support to address the huge breadth of neglected public health crises in developing nations. 

Unfortunately, this issue has relevance to our current novel coronavirus pandemic. The latest report from the Access to Medicines Foundation shows that coronaviruses are among the 49 priority diseases, conditions, or pathogens for low to middle-income countries for which the world’s top 20 pharmaceutical companies lack research and development projects.

In a recent op-ed, Ellen ‘t Hoen, lawyer and director of Medicines Law & Policy, provided a chilling warning about our response to the current Covid-19 pandemic:

“Let’s not repeat the horrific delay in access to life-saving medicines that happened with HIV treatments. In the ‘80s, massive government research efforts and public investments accelerated the development of antiretroviral drugs.
This public spending turned HIV from a death sentence into a chronic disease in high-income countries that could afford drug prices of $15,000–20,000 per patient per year. The millions of people suffering from HIV/AIDS in the developing world were initially left out in the cold.
The pharmaceutical industry, patents in hand, defended their market exclusivity, which barred lower-priced generic versions from becoming available. It
took global campaigning and international action for this situation to change.”

How research is regulated

While it’s tempting to lay blame on individual ‘bad apples’ gaming a system for profit, it’s important to note the larger capitalist systems allowing for profit-based interests to dominate.

Sure, we can educate clinicians to look more closely at the scientific literature they use to inform their practice. But in often-overwhelmed healthcare systems, healthcare workers rarely have the time—or adequate information—to really scrutinize scientific findings. Ideally, clinicians should be able to trust published scientific evidence and the judgement of regulatory bodies.

Medical journals have a part to play by setting higher standards for transparency of authorship, conflicts of interest, and protocols. Yet journals will always have some limitations to their knowledge of what data is being withheld or misrepresented.

Independent reviews that look for risk of bias, such as those provided by the Cochrane Collaboration in our Tamiflu story, are also integral ‘checks’. But independent reviews take time. It’s unsustainable to constantly play catch-up with pharmaceutical companies working with larger budgets and established medical influence. 

While healthcare providers, researchers, and even patients can all play some part to combat profit-driven medical science, larger regulatory reforms are needed to fully address this. In his book ‘Private Profits versus Public Policy: The Pharmaceutical Industry and the Canadian State’ physician-researcher Joel Lexchin outlines how neoliberal policies have deregulated the pharmaceutical industry in the name of preserving international industry competitiveness.

This has led Health Canada—meant to be an industry-independent regulatory body—to place “safety at a lower priority than its mandate to get new drugs on the market”. Pharmaceutical companies now face fewer marketing regulations and little scrutiny for their products’ claims, as clinical trial data is treated as protected ‘intellectual property’ rather than scientific evidence to be critically assessed.

The treatment of medical research as ‘intellectual property’ also means that essential science for new treatments can be withheld from wider use. Critics say this delays the development and availability of life-saving treatments, with some fearing it will impede timely and global access to a Covid-19 vaccine

If regulatory bodies aren’t scrutinizing the evidence for safety and efficacy, this sets a concerning standard for the state of health research and policy-making. While Lexchin’s research focuses on Canada, these deregulation trends mirror those seen around the world.

In our story, we discuss evidence that policy and regulatory decisions at the WHO and CDC were both influenced by industry interests. If we truly want to combat the types of biases outlined above, the regulatory bias towards industry interests must be reversed at the governmental level.

As Fabbri et al. 2018 suggest, policy actions must go “beyond disclosure” policies for conflicts of interest and include “increasing funding for independent research and strict guidelines to regulate the interaction of research institutes with commercial entities.” As long as profit is a central component of health research and care, we will continue to see financial interests put before public health and safety.