1. Provide the title of your story or series and the names of the journalists involved.
Series of four related breaking news stories from Barnes' designated coverage beat on Pharmawire.com and BioPharmInsight.com:
1."AstraZeneca's Brilinta: Wednesday's FDA Advisory Panel may yield surprises" – sources
2. "Boehringer Ingelheim's Pradaxa/AstraZeneca's Brilinta: Premature inclusion in ESC guidelines bodes well for EU approval" – clinicians
3. "AstraZeneca: FDA scrutiny over Brilinta's EU data may delay approval" – sources
4. "AstraZeneca's Brilinta in the spotlight as FDA studies key data"
2. List date(s) this work was published or aired.
1. July 26, 2010
2. Sept. 2, 2010
3. Sept. 14, 2010
4. Nov. 19, 2010 [Published on this date on both Pharmawire.com and parent publication FT.com, provided by Pharmawire.com]
3. Provide a brief synopsis of the story or stories, including any significant findings.
I am a specialist pharmaceutical journalist and my "beat" for Pharmawire.com and BioPharmInsight.com is to provide global coverage of key drugs moving through the pharmaceutical pipelines and undertake investigatory reporting to provide forward-looking news reports on material events involving these developmental drugs that shed light on how the material outcomes might impact the companies involved. My beat involves three expert areas of therapeutic coverage: cardiovascular disease, endocrinology/diabetes and anti-infectives.
1. The first story picks up on the Brilinta situation ahead of the 28 July 2010 FDA Advisory Panel meeting and the September 16 PDUFA (approval decision date) to report ahead of time how the regulators may view this potential new anticoagulant treatment. Sources close to the situation relayed information that the soon-to-be released FDA documents may reveal some surprises in the Brilinta data and present some uncertainties over the approvability of the drug, which has widely been considered by experts to be a "home run." However, overall optimism remained that the drug still would receive a positive vote from the FDA Advisory Panel given its overall robust mortality data, despite the well-documented difference between the results in the US population and the rest of the world.
2. The second report covers the European situation where Kirsty picked up on signals that indicated that Brilinta would receive a swift and problem free approval process in Europe and an market uptake as the European physician community largely supported the drug based on the European data and the key opinion leaders even went as far as to add the drug to the European cardiovascular guidelines before it was even approved, such was their faith in the product.
3. The third story jumps back in to follow the US approval situation following the positive FDA Advisory Panel vote but prior to the FDA's official decision on the matter. The FDA does not always follow the recommendations of its Advisory Panel, even when the vote is overwhelmingly in favour. Most industry commentators, analysts and high profile physicians following the situation (including the majority of Kirsty's sources) thought that the drug would be approved. Yet Kirsty had two trusted sources close to the situation that provided information of disquiet over the data going on behind the scenes at the FDA and her journalist instinct told her that there was no way the agency would be able to make a decision in time and would have to delay it, which is the story Kirsty ran with against the popular grain.
4. The fourth Brilinta article investigates the situation again in light of the second upcoming PDUFA (FDA approval decision date). Kirsty's article highlighted the fact that the FDA were still not happy with the data and were still investigating the data anomalies and there was still a lot going on behind the scenes with regard to the application, including the fact that the FDA was talking to an expert clinician who was investigating the matter and providing them with information painting some of the Brilinta data in a negative light. The report reveals that the FDA would consider the expert's analysis as part of its approval decision, making it likely that the agency was again not going to be ready to make a decision before the PDUFA. This was against analyst and physician consensus and was the only coverage of its nature providing this unique angle. The big debate about the data until now had also been about what caused the US data to be so different from the combined rest of the world data but this article flips the angle and presents the theory that it is in fact the credibility of the European data that the FDA is scrutinizing.
4. Explain types of documents, data or Internet resources used. Were FOI or public records act requests required? How did this affect the work?
Kirsty used published clinical data to comb over and look for clues as to where potential issues may arise with regulators and also looked at published European guidelines and had been privy to the contents of these guidelines that would recommend favour the drug before they were announced. She also scrutinized a set of documents sent to her by an expert source that contained their detailed critiquing of the data and highlighted a number of red flags that were of concern to the US regulators that were not known publically, and this was to form a basis for the extended regulatory review of Brilinta in the U.S. as these documents had been presented by her source to high level FDA officials.
5. Explain types of human sources used.
Kirsty used a number of long standing sources that she has built up over the years that she knew to be close to the situation and privy to non-public information regarding the drug, the data, the company and the FDA – including lead trial investigators, platelet expert researchers and physicians, FDA advisors, consultants, clinical trial fraud investigators – all of whom could provide valuable pieces of information and confirmation to pull together the pieces of intelligence she had gathered on what was going on behind the scenes with this drug's approval process and report accurately on how the situation may pan out.
6. Results (if any).
1. Upon the release of the FDA documents ahead of the FDA Advisory Panel meeting, surprises in Brilinta's Phase III dataset did indeed emerge, including the unexpectedly large number of patients lost to follow-up in the trial and evidence of sex hormonal adverse effects in a small number of patients. The panel meeting took place on July 28, whereby these issues as well as the US data anomaly issue were thrashed out, among other things, but the panel eventually voted overwhelmingly (7 to 1) in favour of the drug's approval, as Kirsty predicted. AstraZeneca's share price rose over 4% on the news.
2. Kirsty's synopsis on the European situation proved accurate when on 24 September 2010 Brilinta (now called Brilique in Europe) received a positive opinion from Europe's Medicinal Products for Human Use (CHMP) for its approval and on 6 December 2010 the European Commission upheld the CHMP's decision and approved the drug for sale in Europe.
3. On Sept. 15, 2010, AstraZeneca announced that the FDA had extended the time it will take to complete its review of Brilinta. The review date was extended by 3 months to 16 December. The "unexpected" delay shaved valuable sales revenue of the drug's predicted forecasts and AstraZeneca's share price dropped on the news.
4. On Dec. 17, 2010, it was announced that AstraZeneca failed to receive FDA approval for Brilinta. The FDA requested more analysis of existing clinical trials data, sending shares down almost 7 percent. Kirsty's extensive coverage highlighted the fact that the FDA was still not happy with the data and were still investigating the data anomalies, likely leading to another delay and gave a detailed synopsis as to why. Analysts and the medical community were all strongly expecting that the drug would be approved this time, especially given that it already received approval in Europe. Pharmawire was the only news service to provide an insightful and accurate forward looking prediction of the behind the scenes FDA deliberations that would lead to this outcome, with detailed critiquing of the data in question based on an exclusive interview with a top platelet expert who was advising the FDA on its decision making. Following this announcement, a google search for Brilinta pulls up Kirsty's story first [provided via FT.com] out of 133,000 results.
7. Follow-up (if any). Have you run a correction or clarification on the report or has anyone come forward to challenge its accuracy? If so, please explain.
There were no challenges to accuracy.
8. Advice to other journalists planning a similar story or project.
Be brave and trust your instincts if you have researched the matter thoroughly and can see a genuine angle no one else can see or wants to see. Respect your sources; prove you can be trusted to handle sensitive documents and information responsibly and report the situation in a way that reflects the contents accurately. If you demonstrate integrity and build trust it is more likely your source will continue to provide you with new information on the situation as it evolves and put you in a position to be on top of reporting insightful updates on the situation as I was able to do in the Brilinta series. Continue to follow up on the situation until you have exhausted all possible material angles. Be persistent with your sources if you know they are holding back information from you although don't cross the line. In this case it took a series of gentle and persistent probes until my source finally spilled the beans to me! Do your homework. If a source provides information that will form the basis of a story, especially a controversial story, check through the information to be sure there is no holes in it and you understand it all completely. In this case my source provided me with a lot of detailed data analyses and rather than simply accepting his conclusions, I crossed checked his data with the original clinical trial data that was published in a medical journal and I did my own calculations to check the figures added up and made sense as slicing the data can be dangerous. Don't be afraid to repeatedly question a source until you are comfortable with the information. I did this with my source over a few weeks, writing back explaining why some parts of his analysis weren't making sense to me and he replied and broke it down for me so that I could understand his train of thought. Once I did this I was satisfied to report his conclusions and base my article around them. Even then, be sure to put everything into perspective by fact checking and cross checking the details with experts rather than just taking them at face value and making your own assumptions about what they mean or what might happen. In this case I checked my source's assertions with many experts, most of whom did not agree. At this point I had a take a decision based on all the information I had collected as to which sources were the most informed but I made sure to balance out the article with the counter arguments provided. Always question whether your sources have any ulterior motivation for the information they provide you and take any conflicts of interest into consideration. Be prepared to lose sources along the way. If your article goes strongly against what the majority of you sources want you to write they may be unhappy with you, as many of my sources were in this case, but you must always pursue the truth and maintain your journalistic integrity while minimising damage to existing relationships. If a source provides you with controversial information and they agree to go on the record this is the preferred situation but make sure they understand the implications of this and are comfortable with any backlash they may receive as a result. Inform them as best as possible in advance how you will present their information to avoid any surprise once the article is published. Disclose to the company involved as many details possible about the information you have obtained and what you intend to publish so that the company has adequate right of reply.