1 Boring Old Man

New EMA policy on access to clinical trial data set to be finalised this week

The European Medicines Agency (EMA) is set to finalise its new policy on access to clinical trial data this week

Out-Law.com

30 Sep 2014

Guido Rasi confirmed to the European Parliament that the EMA’s management board will approve the new policy on Thursday, according to a report by EU news website euractiv.com. A spokesperson for the EMA confirmed to Out-Law.com that the body will release details of the new policy after the management board’s meeting either on Thursday afternoon or Friday. "Our new policy will spell out clearly what will be the principles to gain access," Rasi said, according to the euractiv.com report. "The decisions, however, will always be taken by the EMA. Next Thursday, our management board will approve this new version of the policy. That should give us, from the start of 2015, the possibility to start to actively make data available. By 2016, we should have the first clinical trials data available."

Paul Ranson, a specialist in the regulation of clinical trials at Pinsent Masons, the law firm behind Out-Law.com, said that the EMA is expected to announce that it will, as a first step, make Clinical Study Reports (CSRs) available after product assessment subject to the redaction of identified commercially confidential information. CSRs are documents that contain all the details of a clinical trial that are submitted to regulators by a company seeking authorisation to market a new product.

The EMA previously announced that its new policy would not address issues concerning the disclosure of individual patient data (IPD) generated from clinical trials. Ranson said that the EMA is still engaged with stakeholders in discussing what conditions to impose on access to IPD. However, he said many companies have already adopted their own policies and allow restricted access to IPD using a gatekeeper model, which is where a trusted third party control access to the data and impose privacy safeguards. Some, like GSK, have created their own ‘safe havens’ where certain data can be viewed but not extracted, whilst others, such as Bristol Myers Squibb, are making the data available through a collaborative safe haven, Ranson said. "An important consideration for companies is what is said about data reuse and data sharing in the consent form signed by participants," Ranson said. "This is likely to be more of an issue for past trials as data sharing and reuse can be addressed in the consent forms for new trials."

Earlier this year the European Ombudsman Emma O’Reilly criticised EMA draft plans which she said would, if introduced, allow clinical trials data only to be accessible on screen using an interface provided by the EMA. O’Reilly claimed further "wide restrictions" would apply to how the data could be used, something which the EMA denied at the time. It said it intended to make clinical trial data publicly accessible online and that restrictions it was considering were designed to prevent those who access the information using it for commercial gain.

Competing interests surround the issue of whether and to what extent clinical trial data should be made publically available. Many stakeholders believe that medical research would be enhanced if there was full transparency from the results of clinical trials. However, others believe that at least an element of confidentiality is required to protect the significant investments drug companies make in carrying out clinical trials and developing new drugs. They believe rival companies should not be able to piggy-back on their investment and launch new products onto market at their expense.

Expert in life sciences Helen Cline of Pinsent Masons said: "There is a whole spectrum of benefits that could arise from making the clinical trial process and clinical trial data more transparent from improving the efficiency of drug discovery to the public health benefits.”  Earlier this year, the Council of Ministers and the European Parliament voted in favour of a new Clinical Trials Regulation which will require pharmaceutical companies and other medical researchers to post results of all their European clinical trials on a publicly-accessible database.

Having just spent the year poring over the information from a real clinical trial, I have a better sense of what’s needed to thoroughly vet such a study. None of it is commercially sensitive in the way I understand the terms. The only way it would be commercially sensitive would be if the truth meant the drug couldn’t be as profitable as the maker might like because it wasn’t very effective or had prohibitive side effects – which are the reasons to do a trial in the first place. How effective is it? What are the harms? So I’m not sure what they mean by Commercially Confidential Information.

For an Efficacy evaluation, one needs the a priori protocol which spells out how the study is to be conducted; the outcome variables and what parameters will be collected; and finally  how the data will be analyzed. There’s nothing about commerce in all of that. The Adverse Event analysis requires the rawest form available of the adverse events for each subject – before being transcribed and coded. Again, nothing about commerce in any of that – just the clinical facts.

The CSR [Clinical Study Report [CSR] is a "write up" of the study. If it contains the original protocol and the tables of the raw results for the outcome variables for each subject, it’s fine for the efficacy evaluation. But if it’s simply a summary and only contains the processed or analyzed information, it’s of no use. You can jury rig a CSR just as easily as a paper for publication. So when they throw around the term, CSR, we need to know specifically what’s in it. What’s needed is the protocol and the IPD [individualized participant data]. If they aren’t both there, it’s not data transparency. It’s something else [see it matters…]. So when I read, "new policy would not address issues concerning the disclosure of individual patient data" – I worry. For an evaluation of Adverse Events, one needs the CRF’s [Clinical Report Forms]. We need to know what the evaluator saw and what the subject said – not some compilation or already coded list. I don’t read about that here and so I worry some more.

It was the best of times, it was the worst of times...
^{A Tale of Two Cities, Charles Dickens 1859}

Top Psychiatrist Didn’t Report Drug Makers’ Pay

New York Times

By GARDINER HARRIS

October 3, 2008

One of the nation’s most influential psychiatrists earned more than $2.8 million in consulting arrangements with drug makers from 2000 to 2007, failed to report at least $1.2 million of that income to his university and violated federal research rules, according to documents provided to Congressional investigators. The psychiatrist, Dr. Charles B. Nemeroff of Emory University, is the most prominent figure to date in a series of disclosures that is shaking the world of academic medicine and seems likely to force broad changes in the relationships between doctors and drug makers…

Government reveals $3.5 billion in industry ties to doctors, hospitals

LA Times

By Chad Terhune and Noam N. Leve

September 30, 2014

Opening the book on long-hidden industry relationships, the federal government revealed nearly $3.5 billion worth of payments and other ties that U.S. doctors and teaching hospitals have with drug and medical-device companies. These financial details, published Tuesday under a requirement in the federal health law, have been sought for years by patient advocates and lawmakers from both political parties concerned about conflicts of interest in the medical profession.

Initially, the new federal website includes 4.4 million payments made during the last five months of 2013. More data will be published next summer. Officials said the data cover financial transactions involving about 546,000 physicians and 1,360 teaching hospitals across the country. Consumer advocates hope the increased disclosure will ultimately help curb unethical practices by some doctors who prescribe medications and devices after receiving large sums from manufacturers, possibly putting patient care at risk.

Physicians and academic medical centers defend industry collaboration as essential to advance research into life-saving treatments. They have also questioned the accuracy of the government data. The Physician Payments Sunshine Act was included in the Affordable Care Act that President Obama signed in 2010 amid growing demands for more openness in the U.S. healthcare system, which historically has shielded doctors, hospitals and other medical providers from much public scrutiny…

Those revelations of 2008 were the worst of times because I found out about the rampant corruption in the academic psychiatry pharmaceutical industry alliance. I had become a recluse after my own experiences and I felt guilty for not seeing what was happening in my own back yard. On the other hand, it was the best of times because it explained what had happened in my professional world that was so confusing, and it opened the door to trying to contribute to doing something about it. But looking back, 2008 was a confusing year, to say the least.

The Slow Pace of Success in a "Do Something Congress"

Harvard University
Edmond J. Safra Center for Ethics

by Paul Thacker

February 20, 2013

…

It took more than five years to get it done.

Now that it’s all over, I can tell you it was worth it. This bill will bring some balance back to the relationship between doctors and industry. We need them to work together — industry needs the insight from expert physicians to create the next generation of drugs and devices, and doctors need these products to save lives. But we cannot tolerate companies buying off doctors who put profit before patients.

Years from now, I think people will look back on these reforms — the Grassley/Kohl Sunshine Act — and realize that they made academic medicine better. Few people will know about the staff behind the scenes making it possible. Even fewer will truly appreciate the long hours and great deal of stress we went through.

Even when Congress gets something done, it takes an incredibly long time and years of dedication.

I am personally indebted to him for wiping the vasoline off of my own lenses. I hated seeing what he showed us, but am grateful that it finally saw the light of day. Senator Grassley gets loud Kudos for his work in Congress and the moral strength to pursue it, but Paul Thacker was the one who did the leg work and the head work to make it all happen. I’m absolutely sure that he opened a lot more eyes than just mine with his work, and with his later exposures of ghostwriting when he was with POGO. He reminded us of a medical ethic that had gotten lost in a lot of circles along the way. We owe him so much more than he claims for himself…

The Sunshine Act requires payments made to physicians be reported on a publicly available database [good] including payments for research [good]. But it includes the estimated cost of any medication donated for clinical trials reported as payment to the Principle Investigator. We all know that we want to see the payments made to doctors as an index of Conflicts of Interest. These authors contend that doctors doing Clinical Trials will all look like crooks if this is tacked onto their Sunshine Report. So any investigator studying Solvadi at $1000/dose is going to look bad and he/she might really be a saint.

EU Ombudsman:
Clinical trials face new transparency challenges

eurActiv

Date: 30/09/2014

Medical researchers in Europe are facing new challenges over access to clinical trials data, according to the European Ombudsman Emily O’Reilly. The Ombudsman warning came just month after the EU adopted a new clinical trials regulation, which obliges pharmaceutical companies to share scientific data on new medications submitted for approval to the European Medicines Agency (EMA). O’Reilly said scientific data on clinical trials should be made more transparent, for the benefit of patients, doctors and researchers who need "maximum information about the medicines they take, prescribe and analyse".

The EU Ombudsman, who took office a year ago, held a debate in the European Parliament on Monday (29 September) on the matter with representatives of the pharmaceutical sector, MEPs, health campaigners and the European Medicines Agency (EMA). In May, she sent an open letter to the EMA’s executive director Guido Rasi, expressing concern about a significant change to the agency’s draft transparency policy on clinical trials. The EMA is responsible for evaluation of the safety of medicines before they enter the market, and for monitoring the drugs that are already on the market. The EMA has proposed that future access to clinical trials results should be available "on screen only" for researchers. This version would exclude the possibility of researchers being able to print, distribute, or transfer the information, making scientific analysis of clinical study data "highly problematic" according to critics.

EMA will hold a management board meeting on Thursday (2 October) to adopt its new pro-active transparency policy.

« Read: EU Ombudsman worried over lack of transparency at medicines agency»

Speaking at the Parliament event, the EU Ombudsman stated that she has over the past five months opened three transparency investigations concerning the agency and public access to data.  "I will continue to examine closely whether the EMA continues to be committed to transparency and I’m looking forward to hear the evaluation by Rasi on the challenges he is facing in the area," O’Reilly said. Rasi answered that while the EMA believes that clinical trials data should be transparent, there were some cases where commercial confidentiality applies. US pharma company Abbvie took the EMA to court in 2013 over its disclosure policy but later withdrew the complaint after reaching a settlement with the London-based EU agency, leading to changes in the agency’s transparency policy. Consumer groups and transparency activists branded the change as a U-turn on the agency’s earlier commitments.

« Read: Growing concerns over medicines agency’s proposed rules for transparency »

"Therefore our new policy will spell out clearly what will be the principles to gain access. The decisions, however, will always be taken by the EMA. Next Thursday, our management board will approve this new version of the policy. That should give us, from the start of 2015, the possibility to start to actively make data available. By 2016, we should have the first clinical trials data available," Rasi said.

« Read: Health experts critical of industry’s new transparency rules »

Ben Goldacre, a British physician and author of the best-selling book Bad Pharma, said no one can make informed choices on treatments as long as results of clinical trials are being withheld from doctors, researchers and patients. "This is not about being anti-industry. Academics are just as bad about withholding bad results. The key difference is that it’s only the industry which is actively lobbying against change," Goldacre said, adding that he wants all trials, including retrospectively, registered, that summary results are made available and that the clinical study report is made available to highlight changes in methods.

« Read: Pharma industry tries to mobilise patient groups in clinical trials battle »

Richard Bergström, director general of EFPIA, which represents the pharmaceutical industry in Europe, said the industry has faced up to the calls from society on being more transparent. "We have agreed with our global partners on a global set of principles. Our companies will give data and study reports to researchers. We have committed to do this since the beginning of this year. It’s already up and working," Bergström said. "We are not there yet. These are the early days, but we are really moving," he continued. Margrethe Auken, a Danish MEP from the Greens, who was shadow rapporteur of the clinical trials regulation, said that clinical trials should benefit patients first and foremost. A clinical trial belongs first of all to the patient and to humanity and not the industry, she continued. Auken added that apart from more transparency in clinical trials, she also wishes to see more transparency regarding declarations of interests among policymakers.

ethos \ë-thäs\
noun
      : the guiding beliefs of a person, group, or organization

Smoke This: Pfizer Wants Serious Warnings Removed From Chantix

Pharmalot: WSJ

By Ed Silverman

September 24, 2014

In a boost to Pfizer, the FDA has updated labeling on its Chantix smoking-cessation pill to indicate the drug may not carry the risks of suicidal behavior, a controversial issue that prompted the agency to include a serious warning in the labeling in 2009. The changes are being made to reflect the results of various studies. One study involved a so-called meta-analysis of five studies involving nearly 2,000 patients that Pfizer says did not show an increase in suicide thoughts or actions among people who took Chantix compared with a placebo.

The drug maker also pointed to four observational studies of between 10,000 and 30,000 people that did not find differences in risk between Chantix and other nicotine treatments, although these had several limitations [most of the label changes appear on page 3]. The labeling change is welcome news for Pfizer, which hoped Chantix would become a blockbuster but has instead encountered a marketing challenge. Shortly after Chantix was approved in 2006, the drug was increasingly linked in news reports of acts of violence or suicide. The FDA issued successive alerts, the Federal Aviation Administration banned usage by pilots and air traffic controllers, and the Departments of Defense and Transportation restricted use in sensitive occupations. Meanwhile, Chantix sales slid to $648 million last year from $846 million in 2008. And Pfizer settled hundreds of lawsuits last year by people who claim Chantix caused them harm.

The labeling change, by the way, was made on September 19, but Pfizer had not publicly discussed the changes until today, when a watchdog group called the Institute for Safe Medicine Practices planned to release an analysis placing Chantix in an unflattering light and calling for the Black Box warning to be strengthened. The timing of the disclosure of the labeling change suggests that Pfizer sought to mitigate any negative publicity that may have ensued…

Pfizer would like the serious warning, which is known as a Black Box in regulatory parlance, removed, the Associated Press writes. A Pfizer spokesman writes us that the labeling change and upcoming meeting “both serve as a step forward in the process of accurately communicating the clinical and observational data” in relation to serious side effects referenced in the warnings section of the labeling.

Even though the Black Box remains unchanged, Pfizer may benefit to some degree, anyway. How so? The updated labeling now includes new information about the studies in the Warnings & Precaution section. As a practical matter, the Black Box is still front and center, but new language may soften the blow, at least if enough physicians interpret the new information as Pfizer would like. We asked the FDA if the Black Box may be removed and will update you with any reply.

[UPDATE: Thomas Moore, a senior scientist at ISMP, contends the labeling may not help Pfizer very much. "The new studies added to the label provide little new insight into the psychiatric side effects of Chantix. The meta-analysis of suicidal behaviors included only a few of the many clinical studies, was much too small to detect these rare but catastrophic events, and was not published or peer reviewed.  The observational studies had even more limitations. Neither the observational studies nor the meta analysis included the full range of psychiatric side effects reported."]

Meanwhile, ISMP reviewed side effect reports filed with FDA and found that Chantix accounted for more cases of suicide, self-injury or homicidal thoughts than any other therapeutic drug between 2007 and the third quarter of 2013. Moreover, Chantix ranked first in both suicidal and self-injurious thoughts as well as homicidal thoughts, and these reports outnumbered those for any other drug by more than three times. Moore says there is still more evidence that Chantix causes psychiatric side effects. And so the watchdog group plans to ask the FDA to further strengthen the Black Box warning and widen the restrictions on Chantix use to still other occupations. He declined to name those occupations…

There were limitations on some Pfizer findings, as well. The observational studies were conducted after widespread publicity about Chantix and suicidal or hostile behavior, which means patients with a history of psychiatric illness may have been prescribed an alternative treatment. And only reports that resulted in hospitalizations were included, suggesting other incidents were not noted. 

[UPDATE: ISMP’s Moore writes us that "the study of psychiatric hospitalizations omitted 85% of the known psychiatric side effects and depended on diagnostic codes that had not been studied or validated."]

[EDITOR’S NOTE: An earlier version of this story indicated all the observational studies were conducted by Pfizer].

I declare ongoing resentments against Pfizer on any number of grounds: the way Zoloft® was approved by the FDA was insider trading [see [zoloft: the approval III…]; their shameful clinical trial of Zoloft® in adolescents [Wagner et al][see tuning the quartet…]; financing Robert Gibbons’ recurrent attacks on the various Black Box Warnings [see very monotonous…]; promoting Gabapentin [Neurontin®] as a pain medication [E-mails suggest Pfizer tried to suppress study on drug]; but mostly for their ads that put the phrase "chemical imbalance" into the public register.

The labeling change, by the way, was made on September 19, but Pfizer had not publicly discussed the changes until today, when a watchdog group called the Institute for Safe Medicine Practices planned to release an analysis placing Chantix in an unflattering light and calling for the Black Box warning to be strengthened. The timing of the disclosure of the labeling change suggests that Pfizer sought to mitigate any negative publicity that may have ensued…

The meeting when the EMA will deliver their formal policy for Data Transparency is just a week away. Earlier, I’ve mentioned my apprehension about what they might say [the other shoe…] and given an outline of the kind of data that might be involved [it matters…]. Several of years ago, I was pointed to some of the original trials of Imipramine from before they were required by the FDA [remembrance of things past…, remembrance of things past redux]. Their outcome variable was much closer to the one familiar to all clinicians – they interviewed the patients. They had a placebo control group and the study was double-blinded as in modern trials. They saw the subjects weekly and classified their responses based on the clinical interview:

The results of treatment were assessed as symptom free, greatly improved, somewhat improved, no change, or worse. For the purpose of assessing the value of the drug as a significant therapeutic agent, the first two of these categories have been combined as a good or worth-while result and the other three as a poor result. Patients showing a good result were able to return to their normal activities without undue effort…

A controlled trial was carried out to evaluate the effects of imipramine on endogenous and reactive depression. In endogenous depression 74% of cases showed a good response to the drug, while 22% responded to the placebo [P<0.01]. In reactive depression 59% responded satisfactorily on imipramine, as compared with 20% on the placebo [P<0.02]. On comparing these results with those of a previous trial of iproniazid the impression was obtained that imipramine was the more effective agent in treating endogenous depression.

It would be the naive person, indeed, that was unaware of the increasingly blurred boundary between commerce and medical practice. Yesterday at a charity clinic in a very rural community, over 10% of the patients I saw asked if Cymbalta® was right for them. Being asked that repeatedly is bad enough. But what’s worse – I  don’t  can’t even know the answer. It feels like a pincer move – living between a contaminated literature and a successful Direct-To-Consumer ad campaign. Throw in ineffective and complicit professional organizations, an academic community that is often asleep, the restrictions from third party payers, and the accusations of activists, and sometimes you just want to throw up your hands and surrender. And sadly, many physicians [and patients] have done just that.

Adverse Events Caused by a Drug Warning?

Medscape Psychiatry

by Robert L. Findling, MD

July 31, 2014

"Hello. I’m Dr. Robert Findling, Director of the Division of Child and Adolescent Psychiatry at Johns Hopkins University and a vice president at the Kennedy Krieger Institute in Baltimore. The US Food and Drug Administration [FDA] issued a warning in 2004 that treatment with antidepressants could lead to an increased risk for suicidality in young people. Today I will talk about a new study that examined the impact of this FDA warning. This article was published in BMJ, and the first author is Christine Lu."

"Suicide in teens is not only tragic but is a leading cause of death in youngsters. A major risk factor for suicide is depression, so safe and effective treatments for depression are needed. Among high school students, 8% say that they have attempted suicide, and 30% of those youngsters have made a suicide attempt that required medical attention. Suicidality in teenagers is all too common. Moreover, it is associated with a reasonably high rate of morbidity and a real risk for mortality. For that reason, it’s important to consider events that could alter the rates of suicidality. The impact of the FDA warnings has already been examined. This paper asks more and different questions…"

 

"What did the study find? First, there was a 31% reduction in the rate of antidepressant prescriptions. Second, there was an increase of 21% in the rate of psychotropic drug poisonings in adolescents. Finally, the study did not find an increased rate of completed suicides. An accompanying editorial commented that the net effect was that the FDA warning led to more harm. The data from this study suggest that adverse events not only can occur from medicines but also as a result of warnings. This leads to the unanswered question: How do we communicate treatment-related outcomes and treatment-related concerns effectively and openly to ensure improved patient outcomes without unwanted consequences? I’m Dr. Robert Findling. Thank you for watching."

They’re all similar, the studies purporting  to either refute the warning or to say that it has caused harm. They seem to all rely on some large population study with a proprietary database showing that suicidality hasn’t fallen or has actually risen in the aftermath of the warning. They all document that the prescription of antidepressants to adolescents has fallen since it was issued [or at least not continued to rise]. The authors are an odd lot: adult psychiatrists, statisticians, bio-mathematicians, a conservative think-tank, etc. They imply that the Black Box warning resulted in withholding needed treatment from depressed kids. Like the Medscape presentation above, they leave out the fact that any literature that suggests that these drugs are effective in adolescents show minimal effects [if any] and are notorious examples of the experimercials of the era [eg Paxil Study 329]. They have resulted in multiple settlements against pharmaceutical companies for damages and false advertising.

So is there some evil genius in the background pulling the strings trying to dampen the impact of the warning? or maybe have it removed? Some of it has been PHARMA driven, at least early on, but it’s still coming even after all the antidepressant patents have expired. Dr. Findling may or may not be PHARMA friendly, but there’s no point any more. PHARMA may have started this mess, but they’re long gone now. So my hypothetical evil manipulator isn’t likely in that camp anymore. How about some other source – maybe among the ranks of Managed Care? They certainly stand to gain if people give antidepressants to kids rather than something else that costs the insurers more money [particularly now that the generic antidepressants are widely available and cost very little]. They’re a good candidate and the studies often use their databases. Actually, that’s who the author of the study discussed by Dr. Findling above [Dr. Lu] works for studying cost containment.

But there’s another factor, one suggested by a lot of activists and critics of psychiatry – that psychiatrists just like to give out pills.  Yet another possibility – maybe they really think that antidepressants help depressed kids. I personally think there’s a simpler explanation that doesn’t postulate an arch-fiend in the background or even demonize or dumbify child psychiatrists. They don’t know anything else to do. Seeing the kid frequently and getting to the bottom of the problem isn’t in vogue, nor is it reimbursed. There’s no hospital for the really sick, at risk kids. In the modern world that focuses on diagnostic groups [as in the unitary domain – Adolescents with MDD], evidence-based medicine has no place for the kind of single-case model that asks "What’s wrong in the world of this unique adolescent who is floundering at a time in life when floundering is more rule than exception?" Most of the kids survive, but the consequences can and do play out in problems that persist for a lifetime in the enduring identity formed in the teen years. Dramatic? That’s intentional.

When I looked at Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy on Friday [see don’t ask, don’t tell…], I read the write up in TIME Magazine, and linked the one in the  Chicago Tribune, but I hadn’t gone to the site. It was a videotaped interview with Eva Redei, PhD, the senior author. I transcribed it [above] thinking I wanted to write about it. It’s the kind of exaggerating I just hate. But once I heard it, I went back and looked at the article itself. In don’t ask, don’t tell… , I had been sarcastic: my blog title, their small sample size, the pay for publication online journal, I made fun of needing a test to know if you’re depressed [or better]. Maybe I looked back at it because I felt guilty about being so sort of nasty. I know I planned to pan that interview, which I thought was a sham, particularly the  plague-of-depression ending. So I read it through again, looked at the tables, and instead of softening, I went from sarcastic to bombastic.

Your don’t need to hear another rant, so I thought I’d just stick to the sleight of hand that set me off. These two tables below are from the article with a few additions of my own – the red highlighting, and the columns and headers in shades of salmon: The upper table has the BASELINE data for control and MDD subjects and the lower one is both groups at 18 weeks:

Paired t-tests are a form of blocking, and have greater power than unpaired tests when the paired units are similar with respect to "noise factors" that are independent of membership in the two groups being compared…

A paired samples t-test based on a "matched-pairs sample" results from an unpaired sample that is subsequently used to form a paired sample, by using additional variables that were measured along with the variable of interest. The matching is carried out by identifying pairs of values consisting of one observation from each of the two samples, where the pair is similar in terms of other measured variables. This approach is sometimes used in observational studies to reduce or eliminate the effects of confounding factors.

If you go to the doctor for this test, be sure that you take an age/sex/race matched friend who’s not depressed to act as your matched control – it’s sort of a "buddy system"

If someone actually really found a blood test that accurately correlated with depression, including being able to discriminate active depression from the trait of being a depressive, the American Journal of Psychiatry, the British Journal of Psychiatry, and JAMA Psychiatry would be fighting over the chance to publish it. It wouldn’t be tucked away in a pay-for-play online journal. It would already be in the PsychiatricNews and the author would be being bombarded with speaking engagement requests. That’s certainly not what we have here…

EU agency lifts lid on drug data secrets

Reuters

By Ben Hirschler

July 15, 2012

Europe’s medicines regulator, criticised in the past for excessive secrecy, is opening its data vaults to systematic scrutiny in a move that will let independent researchers trawl through millions of pages of clinical trial information.The change is a landmark in transparency that puts Europe ahead of the United States, according to critics of the $1 trillion-a-year global drugs industry, who have long argued for full access to trial data. Such information is a treasure trove for scientists wanting to test drug company claims and potentially expose product deficiencies. As part of a process of opening up, the European Medicines Agency (EMA) plans to hold a conference in November to consider ways of making large data sets available rapidly and routinely to outside investigators…

But then in May the EMA released a draft of their proposed policy, and a pale fell over the land. It wasn’t the promised open data access. Besides a restrictive application process and the specter of redactions, it required using a screen-only interface. By then, our RIAT group had been using such a system or months and I can attest to the difficulties, likening it to going to sea to see the world in a submarine using a periscope. Peter Doshi and Tom Jefferson [the Tamiflu group at Cochrane] coined the term "U-Turn" to describe this change of heart and there was a universal outcry. Looking back,  I could write about little else [posts catalogued below in case you care to review what happened]. At the time, the general suspicion was that the EMA had made concessions in settling with AbbVie and InterMune. The European Ombudsman got involved and initiated an investigation:

In response to the general alarm, the EMA reconsidered and pledged to drop the restrictions. But when the day came to announce their final policy, they postponed things until October, saying:

Management Board delays formal adoption of EMA publication of clinical trial data policy to October 2014

Further discussion required on wording and practical arrangements

European Medicines Agency

Press Release

09/07/2014

The Management Board of the European Medicines Agency [EMA] has postponed formal adoption of the policy on publication of clinical trial data to its 2 October 2014 meeting. Further clarifications on wording and practical arrangements will be discussed by Board members, who have confirmed their general support to the overall aims and objectives of the policy, including the more user-friendly amendments proposed by EMA Executive Director Guido Rasi that would allow data to be downloaded, saved or printed for academic and non-commercial research purposes…

… so there was little to do but wait:

For the last several months, the climate has been less filled with optimism – more an uneasy waiting with the vague concern that "the other shoe was about to drop." This week, there was a development that didn’t inspire any confidence. The new administration of the European Union is moving the EMA with the responsibility for drug and device approval from the Health Ministry to the Ministry of Enterprise and Industry [I should say, back to the Ministry of Enterprise and Industry where it had been before]. I don’t understand the workings of the EU well enough to know the ins and outs of exactly what that means, but it certainly feels like that "other shoe" dropping to me. I don’t have any idea if that has an ominous portend for the Data Transparency policy due in just two weeks, but it sure raises the question. And it makes one worry that the earlier postponement was about more than "wording and practical arrangements":

I’m aware that I tell this story as if it is a Masterpiece Mystery or a Machiavellian court drama, but I come by that quaisi-paranoia honestly. The pharmaceutical industry may have moved on from the psychiatric drug arena, but they’ve left a legacy of disreputable wheelings and dealings that is inescapable. PHARMA doesn’t want Data Transparency, and I would expect them to use every bit of their considerable power and financial resource to undermine it wherever possible. Without the cloak of secrecy surrounding Clinical Trial results, none of the CNS blockbusters of the last few decades would’ve ever left the gate. And that’s likely true as well industry-wide with other drugs.

Glaxo Found Guilty of Bribery in China:
Can Witty Rehabilitate the Drug Maker?

Pharmalot: WSJ

by Ed Silverman

September 19, 2014

After months of anticipation, a Chinese court found the GlaxoSmithKline subsidiary in China guilty of bribing doctors, hospital officials and other non-government personnel, and fined the drug maker more than $490 million, The Wall Street Journal reports. This becomes the largest such penalty levied on a company in China. At the same time, Mark Reilly, the former head of the Glaxo unit in China, pleaded guilty to bribery-related charges and was given a three-year suspended sentence. There are varying reports, however, whether he will be deported or required to remain during that time. Four other senior Glaxo managers in China also received suspended sentences of between two and four years…

The court decisions cap a tumultuous episode for Glaxo, which was already struggling to restore its image and revamp business practices in the wake of a $3 billion settlement with U.S. authorities two years ago. The drug maker had been accused of failing to disclose clinical trial data for certain medicines and improperly marketing drugs, among other things.

Andrew Witty, the Glaxo chief executive, issued a brief statement: “Reaching a conclusion in the investigation of our Chinese business is important, but this has been a deeply disappointing matter for GSK. We have and will continue to learn from this. GSK has been in China for close to a hundred years and we remain fully committed to the country and its people.” [here is the official apology, too]…

Glaxo previously acknowledged investigating claims employees bribed doctors in Poland, Iraq, Syria, Jordan and Lebanon. Meanwhile, the FBI and the U.S. Securities and Exchange Commission are probing its activities in China. As part of a probe into the pharmaceutical industry, U.S. authorities have been eyeing its overseas dealings since 2010 for possible violations of the Foreign Corrupt Practices Act. And the U.K.’s Serious Fraud Office is also conducting an investigation…

Lest you are feeling sorry for Sir Andrew Witty and GlaxoSmithKline, you might want to check out this bio from Forbes with his 2012 Financials:

And if you’re a stickler for dates, you might notice that his Presidency of the EFPIA [European Federation of Pharmaceutical Industries and Associations] ended in July 2013 which happens to be right after the damning leaked memo [a closing argument…, in the shadows…] outlining their plan to undermine the EMA [European Medicines Agency] Data Transparency efforts [which may have succeeded] [see abuzz over there…, a coup d’état…].

It is worth noting that Witty has now spent half of his six-year tenure trying to overhaul business practices, and has still more fines and investigations to show for his efforts. Granted, cultural differences require varying approaches to success around the world, and Glaxo is not the only drug maker facing this challenge. But Glaxo is now something of a poster child for scandal.

Witty has made headway in other areas. In particular, he has won kudos for his push to make clinical trial data more readily accessible to researchers, a move that has helped Glaxo deflect much of the criticism leveled at the pharmaceutical industry otherwise. In trying to resolve this highly contentious issue, he placed himself and Glaxo in a leadership position. And Witty is cutting ties between compensation for sales reps and the number of prescriptions that doctors write for Glaxo drugs

Whether he emerges unscathed by the latest developments in China – and unfolding events elsewhere – remains to be seen, of course. But Witty may need to have Glaxo executives practice some of the self-criticism that Chinese Communist Party leaders preach as a path toward rehabilitation.