Regulations have improved since thalidomide but drug scares are still possible

Wendy Lipworth, University of Sydney

The thalidomide tragedy, which resulted in thousands of deaths and disabilities in the late 1950s and early 1960s, changed medicine forever. One of its outcomes was the establishment of more robust mechanisms for the regulation of medicines and medical devices.

Regulatory bodies – including the Therapeutic Goods Administration (TGA) in Australia, the Food and Drug Administration (FDA) in the United States and the Medicines and Health care products Regulatory Agency (MHRA) in the United Kingdom – now decide which products pharmaceutical and medical device companies can market. They also monitor the safety of medicines and devices once they are on the market.

There is no doubt that the tightening of regulation has prevented countless deaths and disabilities, and saved many lives. But regulation cannot always protect us from harm and events disturbingly similar to the thalidomide tragedy continue to occur. Let’s look at two recent examples.

Vioxx pain drugs

In the 1990s, a new class of anti-inflammatory medicines emerged – the “COX 2 inhibitors”. These pain drugs were touted as being less likely to cause gastric ulceration than existing treatments.

One of these, rofecoxib (Vioxx), manufactured by Merck, was later withdrawn from the market, when it emerged that it increased the risk of myocardial infarction (heart attacks).

Vioxx increased the risk of heart attacks.
Reuters/Mike Segar

It emerged that the company had deliberately misinterpreted and concealed some of the information it had about these risks, thus delaying the withdrawal of Vioxx from the market.

Questions were also raised about conflicts of interest – on the part of academic researchers who collaborated with Merck in running trials of Vioxx, members of the data safety monitoring board whose job it was to monitor trials of Vioxx, and members of FDA committees who assessed Vioxx.

A number of class action lawsuits have followed, including one in Australia in 2010, which ruled against Merck. This decision was subsequently reversed, but this was because the judges decided it was not possible to causally link the particular claimant’s heart attack to his use of Vioxx.

Merck has subsequently come to a settlement agreement with Australian patients.

DePuy hip replacements

Yet another class action lawsuit concluded in Australia this June. The action was brought against DePuy International Ltd and Johnson & Johnson Medical Pty Ltd, which were accused of being negligent in their design, manufacture and supply of a particular kind of hip implant.

The story leading up to this will sound familiar: a promising new medical device – the DePuy ASR hip implant – was developed and marketed in the mid-2000s. The company claimed these implants would would reduce friction and wear, and improve patients’ mobility.

DuPuy was accused of not properly testing the product.
terekhov igor/Shutterstock

Complication rates soon proved to be much higher than expected. Around 2,000 of the 5,500 Australians who received the device have required, or are expected to require, revision surgery.

The device was finally withdrawn in Australia in 2009 and worldwide in 2010.

The company has subsequently been accused of not testing the implant adequately, and of knowing – and denying – that its device did not meet manufacturing specifications.

As with the Vioxx case, concerns have been raised about possible conflicts of interest on the part of some of the surgeons who recommended the implant to their patients, and the regulators who evaluated it.

Is there more to come?

These two eerily similar events raise the question: can we do anything to reduce the likelihood of similar occurrences in future?

There is certainly scope to tighten our governance of the pharmaceutical and medical device industries, and the behaviour of those who interact with them. We can also make our regulation of new medicines – and devices and surveillance of existing products – more robust.

There are, however, several important limits to our capacity to prevent harms from medicines and medical devices – all of which help to explain why history keeps repeating itself.

First, pharmaceutical and medical device companies are commercial entities which invest billions of dollars in developing new medicines and devices. Tight regulations are in place and outright fraud is fortunately very rare.

The commercial imperative is, however, powerful. As a result, there is always the possibility that studies of new medicines and devices will be designed, and their results interpreted and disseminated, in a manner that overstates their benefits, and underplays their risks.

Conflicts of interests may affect the reporting of scientific data.
Bullstar/Shutterstock

Second, most patients who are injured by medicines and medical devices sustain these injuries in the course of routine medical or surgical therapy – either because of unpredictable adverse events, such as allergic reactions to antibiotics, or because of unintended medical errors.

The adage that “all medicines are poisons” is, unfortunately, true, and we need to accept that even the best physicians and surgeons are only human and will inevitably make mistakes.

Third, we need to balance our desire for innovation and access to new technologies against our desire for safety and control. While there is definitely room to improve regulation and surveillance, we don’t want our clinicians and regulators to be so risk-averse that health technologies cannot make it onto the market or survive once they get there.

Finally, while we might like to think that academic researchers, clinicians and regulators are committed solely to their the pursuit of knowledge, patients and the general public, the reality is they all need to earn money, and attract funding for their work. This inevitably creates a situation in which their “primary commitments” compete or conflict with other loyalties or with self-interest.

We need to accept that “conflicts of interest” are part and parcel of all social roles. Therefore, there will never be a group of people whose only commitment is to protect patients.

When this sobering fact of human nature is combined with the dangers of the commercial imperative, the inevitability of unpredictable side-effects and medical errors, and the need to balance our desires for safety against our desire for innovation, the future looks uncertain.

The best we can hope for is that our systems of checks and balances will continue to be refined so that the “thalidomides of the future” will be caught and addressed as early as possible.

Stay tuned for other instalments in the thalidomide series this week.

The Conversation

Wendy Lipworth, Senior Research Fellow, Bioethics, University of Sydney

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

There’s more to Pradaxa’s problems than meets the eye

By Wendy Lipworth, University of Sydney and Ian Kerridge, University of Sydney

Pharmaceutical companies don’t have a particularly good reputation, for some very good reasons. But we can’t let suspicions about the motives of such companies cloud our assessments of drug safety because patients may also suffer.

People with abnormal heart rhythms and other diseases that cause blood clots (thromboses) often require blood-thinning (anticoagulation) medications. For many decades, warfarin has been the most widely used such drug but it’s associated with a risk of bleeding (including fatal haemorrhage) and requires regular blood tests to monitor safety and efficacy.

So the advent of new oral anticoagulant drugs was heralded as a major advance by both patients and clinicians – principally on the grounds that they appeared as effective as warfarin, may be associated with a lower risk of serious bleeding, and are cost-effective because patients don’t need ongoing blood monitoring.

For these reasons, a number of these new drugs, including dabigatran (Pradaxa) and rivaroxaban (Xarelto) were fast-tracked through the regulatory approval processes in the United States and in New Zealand. Continue reading

Abandoning clinical trial safeguards won’t boost local industry

Paul Komesaroff, Monash University; Colin Thomson, University of Wollongong, and Ian Kerridge, University of Sydney

CLINICAL TRIALS – Human clinical trials are an important last hurdle in the development of new drugs and therapies. Today, The Conversation takes a closer look at this vital scientific endeavour with three articles that look at different aspects of the process.


Testing new drugs in clinical trials is a billion-dollar industry in Australia, with most of the money coming from international pharmaceutical companies. But as investment grows in India, China, and other emerging competitors, some people argue we need to make Australia more attractive to such investment. One of their solutions is to water down the ethics approval process.

Responding to these concerns, the Coalition’s election policy on medical research promises to “move swiftly” with reforms to the ways in which clinical trials are conducted, by developing:

a nationally consistent approach to ethical standards to reduce complexity, speed up the process and where possible, rationalise the number of ethics committees to reduce the large number that currently exist.

Before major changes are introduced, however, it is important to remember that ethics committees are the very bodies that ensure the safety of clinical trials and maintain public confidence.

Developed in response to concerns about the untrammelled power of medical institutions in the 1970s, as well as reports of egregious excesses by researchers in the United States and elsewhere, the ethics committee system has become highly refined in both its processes and in the substance of the issues it addresses.

In Australia, it is also remarkably devolved and democratic, drawing in thousands of men and women from different walks of life across the country to engage in conversation, for no personal gain, about ethical issues in health care and research.

Established by hospitals and universities, the panels review research proposals and ensure they’re ethically acceptable. Their deliberations cover potential risks and benefits to both individuals and the wider society and issues relating to consent, confidentiality, privacy, conflicts of interest and protection of vulnerable participants. Continue reading

Of mice and men: role of mice in biomedical research questioned

Christopher Degeling, University of Sydney and Jane Johnson

A study recently published in the peer-reviewed journal PNAS (Proceedings of the National of Academy Sciences) shows that mice are poor models for human inflammatory diseases. The paper, which focused on sepsis, burns and trauma, raises questions about the fundamental role of mice in biomedical research.

Bodily responses to burn injuries and acute infections look similar in mice and humans, but the study authors found they’re driven by fundamentally different genetic and molecular mechanisms. They spent ten years examining which genes in human white blood cells are activated during infection. Data from 167 patients suggested there are particular patterns of genomic change associated with acute inflammation.

After having their paper rejected by several journals, the researchers decided to redesign their study. Apparently, one objection from reviewers was that the results had not been validated by mouse studies. But when the researchers looked at the genomic response to different forms of inflammation in mice, they made a number of startling discoveries:

  1. The relatively uniform gene changes found in human patients were not found in mice.
  2. Genomic changes in mice were completely different to humans, and there was no discernible pattern of gene modification.
  3. None of the mouse models for sepsis, bacterial blood poisoning, trauma or burns predicted the magnitude or direction of inflammation in humans.

These findings have significant ramifications.

Continue reading