1 Boring Old Man

One way to be boring is to become too detailed on a topic, and I’m there right now. The topic is obviously the European Medicines Agency Data Transparency policy released in early October. I did a timeline [European Medicines Agency: a timeline…], but it keeps on going and growing. Here are a couple of pieces that need to be added:

Instead of bludgeoning you with these fragments, I put the timeline on a separate page that you can call up or ignore. I happen to think in "timelines." It’s how I remember patients’ narratives [or for that matter, almost everything else]. So no more fragments. I’ll just put a link to the page when it changes and leave it up to you [TIMELINE].

Another way I think is in pictures, and it’s obvious from my graphics that this process has felt like a game of chess to me. My point in this post is that as monotonous as it may seem, I don’t think the game is yet over. That TIMELINE shows moves and counter-moves, small victories and concessions, gambits and sacrifices, advantages gained only to be out-maneuvered. And the moves still keep on coming. When I first did the timeline [European Medicines Agency: a timeline…], I wrote it like it was over [European Medicines Agency: a disappointment…]. But I was just plain wrong about that. It feels still very much like game on.

One of my favorite books [that I didn’t quite understand] was Gödel, Escher, Bach: An Eternal Golden Braid, a 1979 book by Douglas Hofstadter. One of the central themes of the book was things that are self-referential and recursive – where the same principle is repeated at multiple levels. This is one of those things. The content of the controversy is Data Transparency – insisting that reports on clinical trials are accompanied by access to the raw data rather than having it cloistered behind industry’s claim that they own the data. But if you think about it, this fight over the EMA’s policy is different from past versions, because it’s playing out in real-time, on a closely watched public stage, and it’s playing out Transparently. The fight over the Transparency of Clinical Trial data is being fought with the proxy being the Transparency of the EMA’s process in setting their policy about Data Transparency.

When the Cochrane group went after the hidden Tamiflu data, they did it by going public, joined by the BMJ, later AllTrials, and many others. It went to UK Parliametary Committees, and Parliament itself. When AbbVie and InterMune sued the EMA, one could read of little else. David Healy put up a petition and the blogs whirred. When the EMA quietly released a draft of a policy that was much more restrictive than previously promised, many fronts immediately turned it into a noisy cause célèbre. The EMA backed down somewhat, eliminating the periscope screen-only clause and some of the restrictive application process. Moving the EMA from health to business was announced with no fanfare, but the BMJ, editor Godlee, and supportive MPs were on top of that change like hyenas on fresh kill. President Junckers came around. Now, it’s becoming clear that PHARMA likely had secret meetings or input with the EMA along the way, and the noise is escalating. I anticipate we’ll be hearing about those communications real soon.

Juncked: Plan to move EMA from DG Health to DG Enterprise is abandoned

in-PharmaTechnologist

By Gareth MacDonald

22-Oct-2014

DG Health will keep responsibility for the EMA according to European Commission President-elect Jean-Claude Juncker, who confirmed plans to hand the agency to DG Enterprise have been abandoned.

Juncker u-turn puts pharma in health Commissioner’s portfolio

EurActiv

by Henriette Jacobsen

22/10/2014

The responsibility for the policy on pharmaceuticals was initially put under the supervision of Elzbieta Bienkowska, the Polish Commissioner-designate responsible for the EU’s Single Market, Industry and Enterprises, as well as SMEs. This prompted harsh criticism from the EU health community, and some members of the European Parliament, in recent months, with, for example, the European Public Health Alliance [EPHA] stating that the Lithuanian Health Commissioner-candidate Vytenis Andriukaitis was deprived of a fundamental tool to protect public health.

Speaking in front of the Parliament in Strasbourg on the Commission’s political guidelines, Juncker said he had changed his mind when it comes to health. "Responsibility for medicines and pharmaceutical products will stay with the Directorate-General for Health because I agree with you that medicines are not goods like any other," he said, adding that Andriukaitis and Bienkowska will develop the relevant policy jointly.

The European Consumer Organisation (BEUC) said in a statement that Juncker’s decision is a clear signal to consumers that their health comes before economic interests. “Our efforts have paid off, this is a true consumer victory," the consumer organisation said.

Last month, the pharmaceutical industry denied that it had lobbied to get Juncker to move the industry out of the health dossier. "What we, from the industry, suggested was that the Commission should develop a comprehensive strategy for life sciences to be coordinated. We have not lobbied or expressed a view of how a unit should be structured," Richard Bergström, the director general of the European Federation of Pharmaceutical Industries and Associations (EFPIA), stated.

President Juncker’s moving the European Medicines Agency from the directorate general for health and consumers [DG SANCO] to the directorate general for the internal market, industry, and entrepreneurship [DG ENTR] makes a huge symbolic and practical statement – it’s a seller’s market where  pharmaceuticals are more important as commodities than as remedies for the sick. That’s a completely outrageous assertion.

Our news is filled with the shooting in the Canadian Parliament on Wednesday, overshadowing something pretty important that happened there on Thursday. Bill C-17 passed its third and final reading in the Canadian Senate and will become Vanessa’s Law after receiving Royal Assent. In case you don’t know or have forgotten this story and sponsor Terence Young, here’s a reminder:

1. doing the right thing…
2. a missing link…
3. Terence Young MP…

In particular, 2. discusses the important amendments added to it that make it model legislation for drug safety and clinical trial transparency. So there may be disappointment in the EMA/EU approach so far, but Canada’s about to lead the way down the road we all need to travel. My congratulations to Terence Young MP and his monument to his daughter, dead at 15 from an adverse drug reaction…

It’s impossible to make sense of the timeline in the last post [European Medicines Agency: a timeline…] based only on the facts as presented. What started as an open commitment to full Data Transparency for the Clinical Trials submitted for approval to the European Medicines Agency [EMA] ended with restricted access to redacted partial Clinical Trial reports still under the control of the pharmaceutical sponsor. This particular challenge to PHARMA’s proprietary ownership of the data from Clinical Trials was defeated. But unlike the timeless game of chess in the painting, this contest wasn’t decided on the open field of battle. It appears to have been won in secret in the private chambers of court. It was more like the chess game in Bergman’s allegorical Seventh Seal where the Knight’s opponent was invisible to onlookers – and the outcome was inevitable:

While the losers in such contests often cry "foul play," in this case, it’s already apparent that such a cry is justified. BMJ blogger, Jim Murray [former director of BEUC—the European Consumers Organisation] has been trying unsuccessfully to obtaim the communications between PHARMA and the EMA, but points us to the European Ombudsman’s release of some of those documents from her investigation – confirming that PHARMA had a substantial input in the process:

OCT·2014	In the wake of the release of the final EMA policy, it’s becoming clear that there were significant private communications between PHARMA and the EMA – only some of which have come to light.
	Ben Goldacre: Pharma industry has destroyed its own reputation Undermining the European Medicines Agency’s transparency policy Documents released by the European Ombudsman

Perhaps even more ominous, Fiona Godlee’s letter to Jean-Claude Juncker [new President of the European Commission] makes it clear that the change in the European Commission was a big factor in the EMA’s change in direction:

In 2009, President Barroso finally decided to place Commission policy on health products [medicines and medical devices] and the European Medicines Agency [EMA] under the responsibility of the Directorate-General for Health and Consumers rather than the Directorate-General for Enterprise and Industry. We and many others publicly welcomed this long-requested reform. It constituted an important guarantee that priority had been given to public health and patients rather than short-sighted economic and corporate interests.

An incomprehensible step backwards. Your decision to transfer responsibility for drugs policy and the EMA back to the Directorate-General for Enterprise and Industry is a great disappointment, which none of the groups concerned about public health in Europe can understand. What are the reasons for this step backwards? What will it mean for the future direction of the EMA and for European patients?…

In 2010, the EMA announced a proactive policy on transparency and public access to the data on which the Agency bases recommendations that directly affect the health of European citizens. This policy was in line with an inexorable international trend towards greater transparency and with what MEPs and the European Council wanted to achieve as part of the new regulations governing clinical trials. To the astonishment of observers and of activists who had been deeply involved in this positive development, the EMA made a spectacular retreat in recent months, coinciding with the arrival of the new head of its legal service [whose background was in the pharmaceutical industry]. The EMA explained its change of heart by saying that it had to take into account the Commission’s position in ongoing negotiations on transatlantic trade…

President Juncker’s moving the European Medicines Agency from the directorate general for health and consumers [DG SANCO] to the directorate general for the internal market, industry, and entrepreneurship [DG ENTR] makes a huge symbolic and practical statement – it’s a seller’s market where  pharmaceuticals are more important as commodities than as remedies for the sick. That’s a completely outrageous assertion. [UPDATE: see a change of heart!…].

The support in Europe for Data Transparency justified our hopes for a more positive response from the European Medicines Agency. There have been concrete actions from the British Parliament and its committees. Similar support has come from the European Parliament, and now the WHO is weighing in. Ben Goldacre’s AllTrials petition has signatures from 80,000 scientists, doctors, corporations, organizations, and interested parties. David Healy’s RxISK effort is gathering steam. Dr. Godlee and the bloggers at the BMJ have tirelessly supported Data Transparency as has the Cochrane Collaboration. But for the moment, these collective forces appear to have been outmaneuvered by commercial interests whose access to the seats of power seems to have carried the day.

I was getting ready to write some things about a few new developments in the saga of the European Medicines Agency’s Data Transparency policy, and it occurred to me that the story has gone on so long and become so convoluted that I ought to do a rough timeline. I’d like to say it was for the reader who hasn’t followed the story closely, but the truth is that I’ve followed it closely and there are so many twists and turns that I needed to clarify the sequence of things for myself. It certainly has been a chess game – moves and counter moves, gambits and sacrifices, and it’s still not over. So here’s a rough intro starting with the opening moves through the announcement of their policy three weeks ago with some brief comments, a few posts, and the key links – just hitting the high points:

JUL·2012	The European Medicines Agency announced that they would release their data on approved drugs. It was the first real breakthrough in Data Transparency that I knew about, and it was pretty exciting. Shortly thereafter, GSK finally posted the long overdue data from PAXIL Study 329 [from the NY settlement in 2004].
	any news is good news… EU agency lifts lid on drug data secrets EMA To Make Clinical Trial Data Available
FEB·2013	The centerpiece of this campaign was Tamiflu, a drug stockpiled in case of an epidemic/pandemic. The Cochrane Collaboration questioned its efficacy and wanted to do a meta-analysis on all the trials. The campaign involved Ben Goldacre’s AllTrials, Fiona Godlee and the BMJ, Tom Jefferson and Peter Doshi of the Cochrane group, and many others. Roche finally began releasing the unpublished data.
	good news… Roche Peels Back The Curtain On Clinical Trial Data
APR·2013	Two American companies filed suits contesting the EMA’s plan to release their data, InterMune and AbbVie. The EU court ordered the EMA to temporarily halt its releasing data. It was a decided setback.
	what don’t they understand about the word “All”?… European Medicines Agency receives interim decisions of the General Court of the EU on access to clinical and non-clinical information EMA Ordered Not To Release Trial Data, For Now Transparency Interrupted: The Curtailment of the European Medicines Agency’s Policy on Access to Documents
JUN·2013	A leaked joint memo from the EFPIA [European Federation of Pharmaceutical Industries and Associations] and PhRMA [Pharmaceutical Research and Manufacturers of America] describes an extensive campaign to oppose the EMA’s Data Transparency efforts.
	a closing argument… Big pharma mobilising patients in battle over drugs trials data Exclusive: The Devil is in the Details
SEP·2013	At a meeting in Brussels organized by the PhRMA/EFPIA to clear the air, the air was hardly cleared. AbbVie’s lawyer, Neal Parker, made the case against Data Transparency to the horror of the regulators in attendance. It’s a bit of must watch video [@19:/00].
	a deal-breaker?… Industry and drug regulators disagree on which data should remain confidential
DEC·2013	The European Court lifted the hold on Data Release and asked the companies for justification for their claims. The EMA’s response is in the post.
	another patch of blue…
APR·2014	After negotiation with the EMA, AbbVie withdrew its suit having extracted some concessions on redaction. The naive among us thought it was now something of a downhill run. The wary were on edge.
	a sunny day… European drug trial secrecy case hit by delay AbbVie Drops EU Court Bid to Block Clinical-Trial Data Release UPDATE 1-AbbVie drops legal action in EU drug secrecy case
MAY·2014	The sunny days didn’t last very long. The EMA released a draft of their policy that was dramatically restrictive. Redacted and abbreviated data would be released with a screen-only interface. There was a universal outcry and the European Ombudsman initiated an investigation.
	the U-Turn… EMA’s data sharing policy—towards peeping tom based medicine? EMA policy on publication of and access to clinical-trial data Ombudsman concerned about change of policy at Medicines Agency as regards clinical trial data transparency
JUN·2014	And as we closed in on the date the policy was to be announced, another U-turn. They dropped the screen-only interface part and reassured us that their commitment to data transparency was unwavering. But the wariness had, by this time, spread throughout the land.
	out of the shadows… European Ombudsman reaction to EMA’s 12 June 2014 statement issued after its Management Board meeting EMA’s double U-turn on its peeping tom policy for data release? Is the EMA Making Too Many Compromises on Transparency? EMA has reversed its on-screen restrictions following researcher and citizen protest
JUL·2014	Then, at the 11th hour of announcing their definitive policy, they postponed the release until their October 2nd Board Meeting to get the "wording" right. The Defcon Level rose to wariness²…
	a long hot summer… Management Board delays formal adoption of EMA publication of clinical trial data policy to October 2014 Pardon the Delay: EMA Postpones Trial Data Disclosure Policy, Again
SEP·2014	And while we waited, the other shoe dropped. The new EU President, Jean-Claude Juncker, moved the EMA from the directorate general for health and consumers [DG SANCO] to the directorate general for the internal market, industry, and entrepreneurship [DG ENTR] – reversing the decision of his predecessor. The Defcon Level rose above wariness³ [a major setback]…
	abuzz over there… The European Commission and pharmaceutical policy: A victory for profits over public health? Prescrire and the British Medical Journal send a letter to Jean-Claude Juncker, President of the European Commission letter from the European Public Health Alliance
OCT·2014	When the EMA policy was finally released, it was an certainly better than what had preceeded it [which was nothing], but it was nowhere close to where they started in July 2012. Even more disappointing, it didn’t fully clarify several points eg what does a CSR actually contain? the access to the IPD was postponed, etc. I suppose it could’ve been worse, but it had promised to be so much more…
	beyond the blind… Publication of clinical reports EMA Remains Under Fire for its Policy on Disclosing Clinical Trial Data EMA’s release of regulatory data — trust but verify

Well, the Clinical Trial Cops look to be getting Smart®-er [and you’ve just got to admire yankee ingenuity]. Smart® is a device that takes the "non" out of non-compliance. Your study medicine has a little additive. So you take your pill and push a button, and after 20-30 minutes, it alerts you to blow into the machine. The additive has by then been absorbed and can be detected in your expired breath. If it’s there when you blow, this little machine takes a digital photo and sends it to an online database for facial recognition software to authenticate that the real subject took the pill. Check it out [how it works]! And the company [Xhale] has big plans for use beyond just Clinical Trials as you might imagine. How did I find this peculiar little piece of equipment? Creative use of the Physician Payments Sunshine Act Database. I just looked up a KOL [Alan Schatzberg] and found what he’s investing in. Voila` – Xhale!

SMART^® products have not been cleared for sale or use within the United States. The company is neither soliciting nor accepting any orders for the products. All benefits and claims made are concerning future generations of the product line, which are still under development.

Restoring the pharmaceutical industry’s reputation

by Mark Kessel

Nature Biotechnology 2014 32[10]:983–990.

[full text on-line]

It wasn’t that long ago that the pharmaceutical industry was considered among the most respected industries and Merck the most admired corporation in the United States.

Washington Irving’s Rip Van Winkle slept through the whole American Revolution. I guess I’d done some power sleeping of my own, because we now see PHARMA as among the greediest and most unscrupulous of the lot – from Paxil Study 329 to Gilead’s pricing of Sovaldi and the table from the paper in the last post in which the word criminal appears much too often. Kessel’s analysis of the reason for the change is detailed and contains a lot of food for thought. It’s there for all to read, but here’s where he starts:

Big pharma and big business: To some extent, reputational decline can be attributed simply to the fact that many pharma companies are large multinational corporations that are now facing strategic issues that require an adjustment to the traditional business model. The increasing price and cost pressure, patent expirations on blockbuster drugs leading to aggressive generic competition, public policy and changes in how consumers access medicine are leading to erosion of profit margins. Big pharma, like other industries, is not immune from the pressure of having to meet Wall Street quarterly earnings expectations; indeed, today’s companies are measured on how well their stock performs and boards of directors incentivize management accordingly to meet Wall Street’s demands. The needs of patients are secondary.

Kessel makes an eloquent plea for the value of corporate reputation, and outlines changes that would, indeed, improve both the company’s image and function. But I expect most of the multinational PHARMAs already have a "workgroup" "tasked" with the same thing. GSK has Sir Andrew Witty out front carrying a banner of reform while his Chinese division is bribing physicians to prescribe their drugs. Alex Gorsky of Johnson & Johnson masterminded Risperdal®’s meteoric rise, and now an army of lawyers works to keep him out of a courtroom as they try to cut their losses in the aftermath. In the legal actions, PHARMA settles the government suits rather than allowing them to go to a jury, and later "denies any wrong-doing" – no matter what they admit in the settlement agreements. In the Civil suits, they play the legal chess in the appeal courts when they lose – much like the culture of jail-house lawyers inhabiting our crime dramas.

According to Alexander Brigham and Stefan Linssen of the consulting firm Ethisphere Institute, over the past three decades, the percentage of a company’s value attributable to tangible assets has dropped from 90% to just 25%. Other estimates also suggest that it is the intangible assets of a company [including reputation] that currently represent as much as 40–60% of a corporation’s market capitalization. Thus, a company’s reputation is among its most valuable assets.

My read is that these major pharmaceutical corporations have completed the move from being drug·discovery and drug·manufacturing companies, part of the legitimate health care effort, to being drug·selling cash·cows in the business of "doing business" [in the Bernie Maddof/Enron tradition]. I would suspect any moves they made in the reform arena would be called "brand·building" in their meetings – illusions they definitely know how to create [that should probably be followed with mumbles like at the end of the DTC ads as we watch the cured patients and colorful butterflies]. Meanwhile, here‘s the Forbes’ version of a PHARMA argument lest you’re hoping for anything but the business of "doing business."

Restoring the pharmaceutical industry’s reputation

by Mark Kessel

Nature Biotechnology 2014 32[10]:983–990.

[full text on-line]