GSK: Thou Shalt Not

The recent settlement agreement between British pharmaceutical giant GlaxoSmithKline and a number of US states has been posted online - it makes interesting reading.

In a nutshell, GSK will pay $105 million to settle claims with California, New York and more than 40 other states that it illegally promoted asthma and antidepressant drugs.

It's only when we look at the terms of the settlement that we see how Glaxo have had their hand forced to be more transparent with what they do as a company, including their clinical trial results.

Last year GSK teamed up with AllTrials, an organisation that campaign for clinical trial transparency and support its call for the registration of clinical trials and the disclosure of clinical trial results and clinical study reports (CSRs).

The mainstream media and Alltrials, spearheaded by British doctor and author, Ben Goldacre ,rightly or wrongly, started singing the praises of GSK.

GSK, in fact, were also covering themselves in garlands, professing to be the first pharmaceutical company to release such information.

To outsiders it looked like a major turning point in the field of safe medicines but there are many that are not convinced of GSK's collaboration with AllTrials.

Glaxo announced their collaboration with AllTrials on the AllTrials webpage.

At GSK, we are committed to being transparent with our clinical trial data to help advance scientific understanding and inform medical judgment. We already publicly disclose a significant amount of information about our clinical trials. We register and post summary information about each trial we begin and share the results of all our clinical trials – whether positive or negative – on a website accessible to all. Today this website includes almost 5,000 clinical trial result summaries and receives an average of almost 11,000 visitors each month. We have also previously committed to seek publication of the results of all of our clinical trials that evaluate our medicines to peer-reviewed scientific journals.

Expanding on this, we have committed to make CSRs publicly available through our clinical trials register. From now, we will publish CSRs for all of our medicines once they have been approved or discontinued from development and the results have been published. This is to allow for the data to be first reviewed by regulators and the scientific community. Patient data in the CSRs and their appendices will be removed to ensure patient confidentiality is maintained.

In addition, while there are practical challenges, we also intend to publish CSRs for clinical outcomes trials for all approved medicines dating back to the formation of GSK. This will require retrieval and examination of each historic CSR to remove confidential patient information. Given the significant volume of studies involved, we will put in place a dedicated team to conduct this work which we expect to complete over a number of years. Posting will take place in a step-wise manner, with priority given to CSRs for its most commonly prescribed medicines.

Separately, we are also working to develop a system where researchers will be able request access to detailed anonymised patient level data that sit behind the results of our clinical trials to enable additional scientific inquiry and analyses to help further scientific knowledge.

Back slaps all around then.

Their announcement came on the back of a $3-billion U.S. settlement in 2012 over misleading information about some of its drugs.

A few days ago Glaxo also settled with a further 44 US states. The settlement terms being pretty much the same as the terms they agreed to in 2012.

Let's take a look a some of those terms.

CLINICAL RESEARCH

The following subsection shall be effective for eight years from the Effective Date of this Judgement.

GSK shall report research in an accurate, objective and balanced manner as follows and as required by applicable law.

GSK shall register GSK-sponsored Applicable Clinical Trials beginning after the Effective date with the applicable registry and submit results of GSK-sponsored Applicable Clinical Trials completed after the Effective date to the registry and results data bank as required by the FDA Amendments Act of 2007.

For any GSK product, GSK shall also post on GSK's clinical trial registry any observational studies or Meta-analyses conducted by GSK that are designed to inform the effective, safe and/or appropriate use of any GSK product.

Remember, this 2014 agreement is pretty much in-line with the 2012 agreement GSK made with the US Department of Justice.

On GSK's promotional activities, the judgement/settlement states...

The following paragraphs D through F shall be effective for a period of eight years from the Effective Date of this Judgement.

D. GSK shall not make in a promotional context a representation, or suggestion, not approved or permitted for use in the labelling or under the FDCA that a GSK product is better, more effective, useful in a broader range of conditions or patients, safer, has fewer, or less incidence of, or less serious side effectsor contraindications than has been demonstrated by substantial evidence, or substantial clinical experience whether or not such representations are made by comparison with other drugs or treatments, and whether or not such a representation or suggestion is made directly or through use of published or unpublished literature, quotations, or other references.

E. GSK shall not promote any GSK product by use of Promotional Materials that...

1. Contain a drug comparison that represents or suggests that a drug is safer or more effective than another drug in some particular when it has not been demonstrated to be safer or more effective in such particular by substantial evidence or substantial clinical experience.

...

...3. Present information from a study in a way that implies that the study represents larger or more general experience with the drug than it actually does or

4. Uses statistics on numbers of patients or counts of favourable results or side effects, derived from pooling data from various insignificant or dissimilar studies that suggest either that such statistics are valid if they are not or that they are derived from large significant studies supporting favourable conclusions when such is not the case.

F. When presenting information about a clinical study regarding GSK products in any Promotional Materials, GSK shall not do any of the following for information that may be material to an HCP prescribing decision:

1. Present favourable information or conclusions from a study that is inadequate in design, scope, or conduct to furnish significant support for such information or conclusions.

2. Use the concept of statistical significance to support a claim that has not been demonstrated to have clinical significance or validity, or fails to reveal the range of variations around the quoted average results.

3. Use statistical analyses and techniques on a retrospective basis to discover and cite findings not soundly supported by the study, or to suggest scientific validity and rigor for data from studies the design or protocol of which are not amenable to formal statistical evaluations.


Now, let's take a look at some GSK spin.

Earlier this year GSK's Deidre Connolly wrote a piece on the Harvard Business Review blog entitled 'Bonuses Should Be Tied to Customer Value, Not Sales Targets'

She writes...

Critics may say it took a settlement with the U.S. Department of Justice over past sales and marketing practices to reach that conclusion. But we dropped sales targets well before the settlement, recognizing that traditional sales incentives were out of line with society’s expectations for our industry, and we had to change. Ultimately, past practices affected customer trust and satisfaction and, as a result, damaged the reputation of our industry.

What Deidre fails to mention is the settlement took nigh on 10 years, during which time GSK would have been making changes. Fact - the whistle had been blown on GSK's illegal promotional activities, they were being investigated. She claims that GSK dropped sales targets well before the settlement - of course they did - they were rumbled. She fails to mention that GSK dropped sales targets during the investigation.

Question is two-fold.

1. Why change something that was working so well for GSK if it wasn't illegal?

2. Why did it take GSK so long to make such changes?

Connolly's spin is typical of GSK being caught with their pants down. It serves one group of people, not us, the paying consumer, not doctors, that prescribe GSK drugs, but shareholders. Those that have a financial interest in GSK.

It's perverse when GSK claim that they are going to be more transparent when they do not offer transparency when writing about their transparency. I hope that makes sense? First time I've used the word transparency twice in one sentence.

Further spin continues on Twitter in the shape of GSK's Mary Anne Rhyne.

Rhyne has often been the spokesperson for GSK, particularly where their product Paxil [Seroxat] is concerned.

Through the years Rhyne has had this to say...

These problems [’discontinuation reactions’] are just the body’s adjustment when you stop taking medicines. It takes more than that to be addictive.
Mary Anne Rhyne
GlaxoSmithKline spokesperson
8/21/2002

Notice the substitution of the word 'withdrawal' for 'discontinuation'

Obviously doctors are very busy people, and their day is packed with patients. The question is how do doctors get information about medicines and new research into treatments and disease, and one of the easiest ways is this kind of presentation [”dine and dash”]. We think this is a benefit to both physicians and patients.”
Mary Ann Rhyne
GlaxoSmithKline spokesperson
11/11/2002

So, in 2002, it appears that Rhyne was all for wining and dining doctors in an effort to get them to prescribe more drugs.

If ‘discontinuation reactions’ occur in patients stopping [Paxil], the majority will experience symptoms that are mild to moderate in intensity, and are usually limited to two weeks.
Mary Anne Rhyne
GlaxoSmithKline spokesperson
2005

This was in answer to reports that Paxil was causing a lot of people severe withdrawal symptoms. "Limited to two weeks"? Who is she kidding!

We follow the law, and we follow government guidelines.
Mary Anne Rhyne
GlaxoSmithKline spokesperson
8/26/2005

[Insert laughter here]

Rhyne is now on Twitter. Below we see her posting a link to Deidre Connolly's piece on the  Harvard Business Review blog. [My response to her, which she never answered, is also included in the snapshot]

So, from collaborations with AllTrials to settlement agreements with US states, GSK have now, seemingly, put their past behavior to bed.

I cannot understand why AllTrials campaigner, Dr Ben Goldacre, would wish to be associated with GSK. In fairness he does chastise GSK. On Twitter he posted the following, once again the question I threw out, along with fellow blogger, Truthman, was ignored.

It's a fair enough question, don't you think?

Why, indeed, would Alltrials wish to be associated with GlaxoSmithKline?

Were they duped into believing that GSK, off their own bat, joined forces because transparency is the name of the game?

Reading all of the above would suggest otherwise.

Sadly, Ben has resorted to name calling on Twitter. A few months ago I asked him to send me a private message via Twitter.

Ben was promoting an updated version of his book 'Bad Science'.

We did, eventually talk via email but nothing came of it.

First time in my life that I've been labelled an 'angry, smeary conspiracy theorist' though.

My only question to Ben still remains unanswered. Why would he want AllTrials associated with GlaxoSmithKline?

The full settlement agreement can be downloaded here.

Bob Fiddaman.