Taking responsibility: putting patients’ needs first

All the work we do to monitor the use and performance of our drugs is done with the safety and well-being of our patients in mind. The best way to illustrate this is to look in depth at two specific cases from 2005.

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Confidence in our products, care for our patients: ADDERALL XR in Canada

ADDERALL XR is one of our most important products and a highly effective treatment for children with ADHD. Along with the original version of ADDERALL, it has been the leading product for this condition, licensed for use in the US since 2001 and for children in Canada since January 2004. But in February 2005 Health Canada suddenly suspended the drug from the market, after reviewing adverse event data we had provided to them as part of routine labeling update. The post-marketing safety data from around the world included 20 reports of people who had died while taking ADDERALL or ADDERALL XR, 14 of them children. There were also 12 cases of stroke, two of which affected children. The evidence available to us suggested that a significant number of the patients concerned already suffered from a structural heart defect.

An important fact was that although the individuals concerned were taking ADDERALL, the rate of reported deaths in this population was no greater than that seen in the general population that were not taking the drug. When the US FDA looked at the same data they had acknowledged this fact and opted to add warnings to the labeling against the use of the drug by patients with structural heart abnormalities. By contrast, the Canadian authorities suspended ADDERALL XR from the market without consultation and with less than an hour’s notice. At the same time, the lack of prior warning left many parents and families stranded without drugs to treat their children. As one child psychiatrist said at the time, ‘We have a crisis on our hands, with frantic patients and doctors scrambling to decide what to do with this decision.’

We passionately disagreed with Health Canada’s judgment and action on this, and immediately appealed against it, invoking an appeal process that had not been used in Canada before. During the next six months a panel of three qualified specialists was convened, bringing independent expertise in the fields of pediatric cardiology, pediatric development and behavioural problems and pharmacoepidemiology. They conducted an exhaustive review of all the clinical and scientific data compiled and presented by both Health Canada and Shire. Thanks in part to the robust and thorough nature of this data the panel was able to conclude that there was no evidence of an increased risk of sudden heart-related death in patients treated with ADDERALL XR compared to the general population or those taking other ADHD treatments. They recommended that ADDERALL XR should be reinstated to the market, along with the labeling changes originally proposed by Shire and implemented in the US labeling. Health Canada quickly adopted these recommendations.

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A team effort

The Shire team co-ordinated the efforts of external medical, scientific and legal experts to compile and present the data and worked with our medical liaison manager, sales people, and communications group to communicate key messages. After six months of hard work, and careful management of this serious crisis, ADDERALL XR returned to the market in Canada on August 26, 2005.

With the benefit of hindsight, we strongly believe we secured the right result. As Greg Flexter, a CR Committee member says, ‘There were three key factors at work here. One was the strength of our own internal procedures, which meant that we had solid and convincing data that we could point people to. Another was the value of constant and open communication – so much so, in fact, that in many cases we have actually strengthened our relationships with specialist doctors and healthcare professionals in Canada. And finally, and most importantly, this whole story is proof of the strength of Shire’s values and the genuineness of our commitment to CR. As I tell my team, as long as we concentrate on looking after the patient, the business will look after itself.’

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Protecting patients: Reminyl in the UK

REMINYL is a Shire medication used to treat mild to moderate Alzheimer’s Disease. As a ‘cholinesterase inhibitor’, REMINYL works by maintaining levels of acetylcholine in the brain and it slows the decline in memory functions in around two thirds of patients. In the UK and Ireland we have the exclusive sales and marketing rights for the drug; elsewhere in the world, it is licensed to Johnson & Johnson.

There are two other drugs in the same class available in the UK, all of which were approved by the National Institute for Health and Clinical Excellence (NICE) in 2000 and 2001. All NHS drugs are reviewed on a four-yearly cycle and when these treatments came up for review in 2005 the industry was not expecting any serious issues, given that there had been no major problems since the drugs were first approved and an increasing number of studies had confirmed their clinical efficacy. It was, therefore, a surprise to be told that NICE was recommending that none of these drugs would be reimbursed for newly diagnosed patients in the future in England and Wales. NICE acknowledged that the drugs were effective but argued that they were not sufficiently cost-effective. This was even more surprising since the general medical consensus is that these drugs are not only value for money in themselves (costing around L1,000 per patient per year), but value for money for the tax-payer, since their use can postpone th need for more intensive nursing and support. They are also economical to prescribe, since if they do not work within six months they are unlikely to work at all and treatment can be stopped at that point.

Clearly this recommendation, if implemented, would impact our business but our first concern was for the patients who had come to rely on REMINYL. It’s very unusual for NICE to make a pronouncement like this unless there is a substitute class of drugs available, but in this case there were no other existing treatments that patients could be prescribed and no likelihood of new ones for at least five years. In fact, without the cholinesterase inhibitors, as one doctor told us, for many of his patients this decision would ‘remove all hope’.

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Joining forces

Faced with this situation, the drug companies gradually joined forces with patient groups and specialists, including the Alzheimer’s Society, Age Concern and the relevant Royal Colleges in an unprecedented alliance on behalf of patients.

The first challenge was to contest the Health Economic model NICE had used to assess the cholinesterase inhibitors, a model that not just the companies concerned, but doctors and economists agreed to be flawed. This was backed up by a high-profile media programme and intense lobbying directed at key decision-makers, both in government, parliament and the health service. New data was submitted to NICE and the government asked for the decision to be reviewed. In December 2005 NICE revised its consultation document and accepted that the drugs could continue to be prescribed in England and Wales for moderate cases of Alzheimer’s and for those already taking the medication. However, the revised recommendation excluded the reimbursement of treatment for patients presenting with mild symptoms of the disease, which could affect up to 100,000 people. This is neither humane nor logical, since it’s been proved that there are considerable benefits from diagnosing and treating the disease as early as possible.

We hope that the pressure that has been brought to bear on behalf of patients will achieve the right outcome as we continue to challenge the NICE recommendation. As John Freeman, the Managing Director of our UK Commercial division says, ‘We’re not giving up on this. These are vulnerable people who have nothing else to turn to and we’re prepared to make a stand on their behalf.’

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CALCICHEW patient, Mrs Bernice Flowers who, with her husband Tom, is also involved in running the East Midlands Group of the National Osteoporosis Society in the UK.

Bonnie Cockhill, Sr Regulatory Affairs Director, led the team compiling our response to Health Canada.

Our Canadian team.

Ask, Watch, Ask, Regulate, Educate.

Mervyn Richardson cares for his wife Beryl who is now into her sixth year of successful REMINYL treatment.

Adam Cohen, Hunter Syndrome patient and ELAPRASE clinical trial participant.

ADDERALL XR was back on the market in Canada on August 26, 2005.