1 Boring Old Man

a·nach·ro·nism  (-nkr-nzm)
noun
1. The representation of someone as existing or something as happening in other than chronological, proper, or historical order.
2. One that is out of its proper or chronological order, especially a person or practice that belongs to an earlier time.
from Latin anachronismus, from Greek anakhronismos a mistake in chronology, from anakhronizein to err in a time reference, from ana- + khronos time]

CME Outfitters Announces Brand New neuroscienceCME Live and On Demand Activity To Launch January 7, 2015:

Remission in MDD

CME Outfitters, along with faculty experts Charles B. Nemeroff, MD, PhD, Roger S. McIntyre, MD, FRCPC, and Michael E. Thase, MD welcome registration for the upcoming neuroscienceCME Live and On Demand Program: Remission in MDD: What Does the Future Hold for Clinicians and Patients?

December 04, 2014

CME Outfitters [CMEO], a leading accredited provider in continuing medical education, announces its upcoming neuroscienceCME Live and On Demand activity, Remission in MDD: What Does the Future Hold for Clinicians and Patients? The live program will launch on Wednesday, January 7, 2015 at 12:00pm ET. Faculty experts Charles B. Nemeroff, MD, PhD, Roger S. McIntyre, MD, FRCPC, and Michael E. Thase, MD will lead an interactive one-hour discussion that will challenge clinicians to reinvent the future of major depressive disorder treatment which includes increased patient participation in the treatment process, measurement-based care and a re-definition of treatment to remission as improvement of all symptoms of MDD with functional recovery. Psychiatrists, primary care physicians, nurse practitioners, physician assistants, nurses, pharmacists, social workers, clinical case managers, and other health care professionals who share the goal of achieving remission in patients with MDD are encouraged to register.

“We have a faculty panel that exhibit some of the brightest minds in mental health care today,” said Jan Perez, CCMEP, CME Outfitters Managing Partner, “It has been a pleasure working with these experts, and I think the viewers are going walk away from this program with many new clinical tactics that they can immediately implement into practice to improve the lives of their patients with MDD.”

At the end of this activity, participants should be able to:

• Evaluate all patients with major depressive disorder [MDD] for residual symptoms with a validated tool at each visit.
• Initiate a treatment plan that involves patient participation to address residual symptoms of depression.

This program will present a lively and interactive one-hour clinical discussion, following by 30 minutes of Q&A via telephone and/or web. Click here for more information about the faculty, financial support, credit information, disclosures, and to register.

• Evaluate all patients with major depressive disorder [MDD] for residual symptoms with a validated tool at each visit.

Recently, there’s a new kid on the block – CAT-D. A couple of years ago, Dr. Robert Gibbons, a statistician teamed up with Dr. David Kupfer [in charge of the DSM-5 Revision] and others to introduce a new test – a computerized scale using artificial intelligence technology to produce a depression index by answering only a few questions on the computer, or a smart phone. It was later revealed that this was a future commercial product, already incorporated, that was in line with the notion of a new "Dimensional" axis for diagnosis planned for the DSM-5 – raising questions about the involvement of the company’s principals, all of whom had a place in the DSM-5 Task Force developing such a commercial product without declaring the COI [see open letter to the APA…]. Since apologizing for not noting that this is a commercial product in their journal articles [Failure to Report Financial Disclosure Information], these authors/entrepreneurs haven’t said much about their instrument, obviously targeted towards screening for depression or following treatment.

At one of the first Grand Rounds, he had someone from the faculty of the University of Georgia. I thought it was a great idea. There hadn’t been much dialog between Emory [Atlanta] and the Medical College of Georgia [Augusta], and this seemed like a good way for us to get together. The lecturer who came had pretty slides, but as he talked, it began to sound like a sales pitch for Mellaril [Sandoz] rather than a scientific presentation. I was  disappointed  appalled. I thought the new Chairman would be embarrassed, but he didn’t seem to be. I left Emory at the end of that year. It was mutual, I think. I just didn’t fit anymore. So I didn’t think about that presentation for a decade. The speaker that day was Dr. Richard Borison, who became Chairman of Psychiatry at the Medical College of Georgia. He was a drug researcher, and I started seeing his name on journal articles, always drug studies…

Over a decade later, Chairman Richard Borison’s Clinical Research Center was "busted" and he was sent off to prison for embezzling millions from the University of Georgia [Drug Money Patients Worsened;  Little Oversight Provided]. But I’m getting ahead of myself. At the time, I was both appalled at having a drug company sponsored infomercial for a Grand Rounds and also understood why the new chairman did it. We were flat broke. Money for training had just dried up and we were literally running on flumes. All of this happened shortly after the DSM-III appeared. Others more in-the-know than I assure me that industry had nothing to do with the DSM-III Revolution – that it was later opportunistism. But I still wonder from time to time.

Editorial

Medical journals and industry ties

by Mabel Chew, Catherine Brizzell, Kamran Abbasi, And Fiona Godlee

British Medical Journal 2014 349:g7197.

[full text on-line]

Zero tolerance on education articles with financial links to industry
The BMJ was one of the first medical journals to seek declarations of competing interests from authors. Our focus is on financial competing interests as we believe these to be the most identifiable. We do, however, understand that competing interests come in many forms and we also routinely ask authors to declare relevant non-financial competing interests. The governing principle has been that transparency is a panacea. We placed faith in this principle, but mounting experience and evidence tell us that we were only half right. Transparency remains essential, but it isn’t sufficient to eliminate bias or perception of bias.

We believe this risk of bias is particularly important for clinical educational articles that are designed to guide patient care, when authors’ biases may be less visible to general medical readers. For some years we have sought to minimise as well as declare competing interests for these articles. Recently we introduced more active management of competing interests, requiring authors to complete a more detailed declaration and excluding authors with close ties. Now we have decided to go a step further, as heralded three years ago. From next year our clinical education articles will be authored by experts without financial ties to industry [box]. By industry we mean companies producing drugs, devices, or tests; medical education companies; or other companies with an interest in the topic of the article. We are phasing in this policy to start with editorials, clinical reviews, and most practice series. We hope that by the end of 2016, this will have extended to the rest of our education section: our specialist state of the art reviews and diagnostics and therapeutics series.

• Competing interest definitions and process for The BMJ’s editorials and education articles [including clinical reviews, practice articles, and state of the art reviews]
• “A conflict of interest arises when a person has a personal or organisational interest that may influence or appear to influence the work they are doing. Usually this is a financial interest, but it may also be non-financial.”
• We ask authors to declare interests in the 36 months before the declaration and those known to be going to occur during the next 12 months
• Authors are asked to complete a form, available at www.bmj.com/sites/default/files/attachments/resources/2011/07/current-bmj-education-coi-formfinal-1.doc. For unsolicited articles, we also ask who prompted submission and whether professional writers contributed
• Each author’s declaration is carefully assessed by the handling editor, and may be discussed at a regular editors’ meeting, to ensure our decisions are consistently and fairly applied by the editorial team.
• We have started publishing authors’ competing interests forms alongside the articles, and advise authors of this when they send their forms. We plan to do so for all editorials and education articles
• From 2015, we will roll out a policy of editorials and clinical education articles authored by experts without financial ties to industry [companies producing pharmaceuticals, devices, or tests; medical education companies; or other companies with an interest in the article topic]

Shift in culture
Why are we doing this? The first reason is that making clinical decisions based on information biased by commercial interests can cause harm, as happened with cardiotoxicity from rosiglitazone and rofecoxib and continues to happen with hydroxyethyl starch. We also believe that the educational content we publish will have more impact if readers can trust it. We know that readers consider research papers written by authors with declared financial links to industry to be less important, relevant, rigorous, and believable; they are also less willing to prescribe drugs evaluated in such papers. Finally, we want to encourage a shift in the culture of medicine. We think that we can help to do this by promoting authors without financial ties to industry and offering them appropriate prominence and visibility.

Financial competing interests are endemic to the culture of medicine and are rarely driven by malign motives or actions. The mechanisms of influence are diverse. An author of a review article might be an advisory board member for companies selling drugs for that condition, a commentator might have received honorariums from industry for lectures on the topic, or an editorialist on a disease might be a patent holder for one of its diagnostic tests. Psychological research suggests that biases may operate subconsciously. Our decisions not to proceed with an article or an author are not made lightly. Nor are they intended to pass judgment on an author’s integrity. However, we cannot ignore the mounting evidence of systematic attempts by commercial interests to corrupt the literature and influence clinical decisions. Internal company documents revealed during litigation expose practices aimed at influencing clinicians such as funding medical meetings, dinners, studies, and articles. Many clinical practice guidelines are little more than industry marketing tools because of the financial competing interests of their authors and sponsors…

And we can’t operate on a bad apples theory. Too many physicians in high places were [are] on board [just look at PROPUBLICA’s Dollars for Docs or the Sunshine Act site]. We have to swallow our disillusionment and assume that enforcable [and enforced] stops will be required to keep it from continuing and/or recurring [same it]. We have now a whole generation of physicians who’ve grown up in this climate, with too many participating, and they need special attention. So it’s not just a matter of putting restraints on industry, it’s equally important to focus on physician collusion and respond decisively.

And as for Dr. Fiona Godlee and her editorial staff at the BMJ – center of right-thinking for a long time: she’s testifying in Parliament, leading in the fight for the Tamiflu data, setting policies like this one, doing everything in her power to lead us out of the wilderness and "encourage a shift in the culture of Medicine." Does this kind of activism count in Stockholm? Do journal editors qualify for Knighthood? Is there some way to recognize her persistence and her savvy in knowing what rocks to look under? Could she be cloned? Fiona Godlee is a definite "keeper."

A level playing field

The Lancet Psychiatry. 2014 1[6]:403.

At The Lancet Psychiatry we aim to publish research that illuminates and changes clinical practice. Changing practice requires a high standard of evidence, although existing practice does not always have a solid scientific base. Management of mental health often seems intuitive, so many interventions have been developed and rolled out on the basis of good intentions rather than good science [eg, post-traumatic stress disorder counselling after natural disasters]. We do not deny the role of clinical expertise and the art of the individual psychiatrist, but we believe that studies aimed at altering the status quo should be rigorous in planning, execution, and communication.

The acknowledged gold standard in terms of research is the randomised controlled trial [RCT], a method that should be applied to all types of intervention, wherever possible. In psychiatry, there are also good pragmatic studies of intervention outcomes where RCTs are not feasible, the most informative being those that combine cross-sectional and longitudinal observations. Excellent work is done using registries, particularly where health-based registries can be linked with others, such as those held by the educational and justice systems. For each type of study, there are recognised guidelines that list what should be measured and reported [compiled by the EQUATOR network]. The best-known is the Consolidated Standards of Reporting Trials [CONSORT] statement. CONSORT is itself evidence-based, and for each item there is an explanation of key methodological issues and the importance of reporting that item. Many medical journals now include CONSORT in their instructions to authors, but the slow rate of progress can be seen by looking at the search results for any meta-analysis — too frequently, studies have to be excluded because insufficient information is available.

Some claim that psychiatry, especially psychotherapy, is not suited to such rigorous approaches. Psychotherapist and author Darian Leader has stated that “the criteria for the evaluation of therapies has moved to a very narrow view of evidence, based on the medical model of randomised-controlled trials … with a control group, and so on. You can’t do that with therapy, because the whole point of therapy involves the beliefs the person has initially about their treatment or therapeutic experience. So you can’t randomly assign someone to a therapist.”

The Lancet Psychiatry admires this focus on the individual, but believes a strong evidence base is both possible and necessary. In the interests of all those who entrust their lives and well being to mental health professionals, it is time to level the playing field. All interventions should be assessed to the same standards of evidence, from psychopharmacology and psychotherapies, to brain stimulation technologies and new approaches such as video games and apps. Trials should be registered in a publicly available database; the protocol should be available, and the methods and results reported must match the protocol to avoid publication bias. Most important, sufficient information should be provided to enable replication of the study. The basis of scientific research is validation and refutation. For compounds, this means chemical composition, formulation, and dosing schedules. For psychological therapies, it means details of how many sessions, the length of sessions, availability of a manual where a specific therapy was given, details about the therapist, and evaluation of differences between specific therapists and sites. For training interventions, it means access to the training material, and details of the trainers, sessions, etc. This approach also applies to models of care: if something has the potential to be useful, it must be replicable. Circumstances will differ and where people are involved there will always be considerable variation, but providing relevant detail will enable other researchers to test the data and perhaps to explain different outcomes. Where trials are not possible, data on outcomes — including those associated with general well being and function rather than specific symptoms — are necessary. One essential set of observations is that of adverse events. Again, there are people who claim that the different nature of medicine and psychotherapy means that, although it is relevant to collect adverse event data for the latter, to do so in the same manner for the former is the equivalent of comparing apples with oranges. However, The Lancet Psychiatry believes that if an intervention has the potential to confer benefit, it also has the potential to cause harm.

This rigour is needed not just to satisfy journal editors but to convince researchers, clinicians, patients, and ultimately governments. If we want mental health services to be free at point of access, we must demonstrate that they work.

Carrier reimbursed psychotherapy didn’t disappear. It was taken over by other mental health specialties with controlled frequency, duration, and negotiated rates of payment. A psychiatrist colleague recently suggested to me that a physician [like me] shouldn’t be a psychotherapist based on a different argument – economics – saying that it costs too much to train a physician and the physician psychotherapist would therefore not be cost effective [the latter part implied].

The acknowledged gold standard in terms of research is the randomised controlled trial [RCT], a method that should be applied to all types of intervention, wherever possible.

The most obvious objection is the extent to which RCTs can be corrupted, manipulated, jury-rigged, etc. The scientific misbehavior in the RCTs of psychiatric drugs is staggering. I could never have imagined anything like it could even happen. So I spend my days involved in trying to insure that the kind of perverse science we’ve seen in psychiatric and other drug research never happens again. At the moment, access to the raw data from trials with independent analysis seems the best approach to what has gone before.

But even without the corruption, there’s more to be said about RCTs. I think they are essential as a beginning take on cataloging the adverse effects of drugs [psychiatric and otherwise], but only a beginning. Many adverse effects come with chronic use, so ongoing reporting is an essential ingredient in any accurate understanding of drug toxicity [for example, David Healy’s Rxisk site].

One might think that cleaning up  the corruption, the distortion, the exaggeration might make RCTs the preferred standard in efficacy studies as well, but I’m not sure that’s totally right either. RCTs can be too sensitive – detecting small effects that are not clinically relevant even if they are statistically significant. They’re limited by their time frame, the outcome instruments, the subject recruitment and evaluation processes, and then there’s the placebo effect. The results are often hard to replicate, thus the increasing reliance on meta-analysis of multiple studies in evaluating overall efficacy.

par·a·digm  (pr-dm)
noun
noun: paradigm; plural noun: paradigms
1. [technical] a typical example or pattern of something; a model.

In Dan’s case, he had a particularly virulent condition. His mind was dominated by an apocalyptic complex delusional system in which he believed he would be called on to be a killer. It was a classical presentation of paranoid schizophrenia or whatever you choose to call it now. But it’s often the least medication responsive and the most likely to be acted on. He needed a vigorous individualized treatment program aimed at what he had, not some commercial enterprise like the CAFE study offering a generic blinded trial of medication. There is no remotely rational justification for what happened in this case.

"The University of Minnesota is never going to conduct an honest and thorough investigation of alleged psychiatric research misconduct."

An excerpt from Leigh Turner’s letter to Minnesota Attorney General Lori Swanson, after Tuesday’s revelations by Niki Gjere:

University officials like to emphasize that Dan Markingson died ten years ago. They claim his case is “old news.” However, if the numerous local citizens that have contacted Professor Carl Elliott and me are credible, and I believe they are, Dan Markingson is one person among numerous victims of psychiatric research misconduct. Some of these victims reportedly were harmed after Markingson’s death. Perhaps treating Markingson’s death in the CAFÉ study as ancient history not worth revisiting has enabled more patients to be harmed. Niki Gjere has the same concern. Asked  by Mr. Baillon about her “greatest fear in the current environment,” she responded, “That it continues to happen. That patients are continuing to be harmed, that nothing’s been fixed.” 

Responsible university presidents investigate reports of research misconduct. Unfortunately, President Kaler functions more as a college mascot – a Goldy Gopher in a suit and tie – than as an accountable leader. The University of Minnesota is never going to conduct an honest and thorough investigation of alleged psychiatric research misconduct. You need to do it. Any additional delays risk putting more vulnerable individuals at increased risk of harm.

Thanksgiving special — menus needed at the EMA’s restaurant

British Medical Journal

by Tom Jeffeson and Peter Doshi

27 Nov 2014

[full text online]

… On 24 November 2014, the European Medicines Agency [EMA] released a new “Guide on access to unpublished documents.” The guide follows in the steps of several other policy documents, charting the revolution from a closed shop to what is probably the most liberal experiment in regulatory data sharing on the planet.

The six page guide is written clearly, as you would expect from a document for “anyone” interested. The guide tells you how to apply for documents held by the EMA as part of the process of central pharmaceutical regulation. We learn that English is almost certainly the language of the released documents, but you can apply in any language of the European Union. Other sections tell you what will happen to your request, and what options you have in the event that your request is turned down or not answered in time.

Readers of the guide are warned that the release of large and complex documents may take place in batches over a long time. This certainly has been our experience and presents a serious problem for independent researchers who work on deadlines. We applied for clinical study reports from trials of a global public health intervention, and we’ve yet to see more than 10% of the text six months after the ball got rolling. The EMA tells us that the documents are in preparation, but so far there’s little meat.

Gone, it seems, are the good old days of data request. On 10 January 2011, we requested around 20 clinical study reports on Tamiflu. By the end of May, the EMA had sent us 25,000 pages of unredacted text. One presumes that the EMA’s workload has exploded since those early days. But is this the case? We await increased transparency on the to-ing and fro-ing with the marketing authorisation holders, to understand more precisely what happens as one waits. Where are the delays occurring? How can the system become more efficient? As we await answers to these questions, we think it’s time to address an equally serious problem: the lack of a menu.

While we applaud the EMA’s efforts to provide a guide that makes requesting documents easier, we are concerned that the guide does not tell us what’s on the menu at the EMA restaurant. For hungry people this is a bit of a problem, but even more so for the restaurateur…

So let’s have a list of holdings by marketing authorisation application, with the dates and types of documents held included. And while you are at it, please explain what’s in each document in plain language so that “everyone” can order the right dish.

It’s easy to see  conceptually why the consensus has settled on having the raw data as a powerful way to put a much needed damper on the massive over-prescription and over-use of medication in medical practice. But it rests on the availability of independent scientists to do the analyses – probably gratis. And that, in turn, rests on how easy this data is to come by and work with. These clinical study submissions each have thousands of pages – challenging in their own right. But in this blog, Tom and Peter are talking about something that comes before anything, knowing what studies are available – apparently no easy task. Only then can one begin the application process [which this EMA guide apparently clarifies].

And it’s not just an issue with the EMA. The various pharmaceutical companies are creating their own unique versions of the conditions and modes of access that might be available for future independent analyses. So, as exciting as the recent advances have been in the fight for public access to the raw data from clinical trials, as is always the case – the devil is in the details. And in the best of circumstances, the process will be hard with long wait times. Even if the NIH/HHS’s recent pledge to make sure that the requirements for posting the results of Clinical Trials on clinicaltrials.gov supplies the advertised result, the trial sponsors still have a year in which to post the data, and even then, it isn’t exactly "raw."

"I think that sunlight is the best disinfectant. All of these things are happening in plain sight, and they’re all protected by a force field of tediousness. And I think that with all of the problems in science, one of the best things we can do is to lift up the lid, finger around with the mechanics, and peer in."

European ombudsman questions European Medicines Agency over AbbVie redactions

by Rory Watson

British Medical Journal. 2014 349:g6904.

The European ombudsman, Emily O’Reilly, has written to the European Medicines Agency asking it to explain by 31 January 2015 the redactions it made in the clinical trial data provided by AbbVie for its best selling drug adalimumab [Humira], used to treat rheumatoid arthritis. The redactions were made as part of the settlement between the agency and the company after AbbVie had gone to court to try to prevent publication of certain clinical trial data.

In her letter O’Reilly acknowledged that “certain redactions may be justified to protect the personal data of patients.” She also accepted that “certain other redactions, which mention the names of companies that provided services to AbbVie, or the names of software used by AbbVie, are not, in my view, problematic, as they may be considered to relate to the confidential business relationships of AbbVie.”

But after examining the original and the redacted versions of the clinical trial data, internal agency communications, and correspondence between the agency and the company, she expressed “doubts and concerns as regards other redactions.” O’Reilly, who opened an investigation into the case in April, identified 16 instances where she wanted the agency to explain why the redactions were necessary to protect AbbVie’s legitimate commercial interests…

Here so many years later, that feeling is still with me. I don’t feel comfortable at all with the Statins for minimal lipid elevations, and don’t take them myself. Nowadays, there’s the added concern about industry interference. Today, on the way home from the clinic, I passed a pharmacy with multiple signs stuck  by the curb advertising vaccines of many kinds, only one of which made sense to me. Last week at a routine physical, my doctor mentioned several that I question. I didn’t say anything [but the look on his face suggested that he was on to my skepticism]. It’s not a big deal to me, but I do think that the many recommendations and reports that are all over the evening’s news are often examples of very small differences – differences that don’t necessarily make a difference.

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Japanese Patients 60 Years or Older With Atherosclerotic Risk Factors

[click for full text]

In the editorial, they review the earlier studies in detail in what seems to be a balanced way and I leave that to you to read for yourself. In my reading all of this, I thought about two things. First, the risk/benefit ration in this case is clear – a baby aspirin a day is near no-risk for the overwhelming majority of people. It is unlikely that this issue gets into Conflicts of Interest or much in the way of industry interference [even if "baby aspirin" costs more than adult doses of aspirin these days].

My point isn’t about baby aspirin. I don’t take them myself, but if I had exertional chest pain, I might. If I ever have an oppressive substernal chest pain radiating down my left arm, I bet I’ll take Aspirin first, then call 911. My point is about the use of statistics in medicine in general. I’m moderately savvy as doctors go about statistics – a numbers guy by nature who likes quantification in almost any flavor. But statistical predictions feel out of hand to me. My specialty, psychiatry, has gone through a very long period where small differences have often been magnified to an outrageous degree and mere statistical significance has been presented as a surrogate for true clinical relevance. It’s not.

EMA’s Top Drug Regulator, Guido Rasi, Forced to Step Down

Regulatory Affairs Professional Society

By Alexander Gaffney, RAC

14 November 2014

In a major development, the head of the European Medicines Agency [EMA], Guido Rasi, has been forced to step down by the EU Civil Service Tribunal after adjudicators found that the European Commission had improperly selected him in 2011. The case against Rasi’s appointment was filed by Emil Hristov, formerly with the Bulgarian Drug Agency and a member of EMA’s board, who maintained that EMA and the European Commission had improperly assembled a short list of candidates for the position of EMA’s executive director after the controversial departure of former executive director Thomas Lönngren in 2010. Hristov had applied to the position, but after reaching the interview process for the interview, was ranked last among eight candidates and was not selected to be on a "short list" of candidates presented to EMA’s Board of Directors as being the most suitable for the position. The assembly of that "short list" of candidates by a selection committee was improper, the court found, and the EMA board should have been able to consider the candidacy of Hristov, who they were familiar with.

Therefore, the selection of Rasi by the European Commission is to be annulled, the court ordered. The decision has immediately ramifications for EMA and Rasi, who has been removed from his position and replaced on an acting basis by Andreas Pott, now deputy executive director of EMA. “I note with regret today’s judgment by the European Union Civil Service Tribunal," said Professor Sir Kent Woods, chair of the Management Board, in a statement. "It is important to remember that the ruling is about a procedural formality. It is not a reflection on Guido Rasi’s competence or ability to run the Agency, something which he has done successfully since November 2011.”

Both EMA and the European Commission are scrambling to see if the decision can be overturned, they said. The departure of Rasi comes at a particularly tricky time for EMA, which is in the process of implementing a massive change in the way it treats clinical data transparency. Transparency has been one of the hallmarks of Guido’s tenure as EMA’s executive director, and his departure could very well derail some of his signature initiatives.

European Regulatory Roundup: Andreas Pott Takes Over at EMA

Andreas Pott Again Tasked with Steadying EMA in Turbulent Times

Regulatory Affairs Professional Society

By Nick Paul Taylor

20 November 2014

Andreas Pott has a habit of being thrust into difficult situations. In 2010, Pott was appointed acting executive director of the European Medicines Agency (EMA) at a time when the regulator was dealing with allegations of conflicts of interest, disputes with the European Parliament and an early row over transparency. Now, Pott is once again in the hot seat during a period of turbulence at EMA. The factors behind Pott’s latest stint as acting executive director relate to the first time he took the role. Back then, Pott held the post during the protracted and messy transition between the reigns of Thomas Lönngren and Guido Rasi. Pott handed the position over to Rasi in late 2011. However, a tribunal has now ruled the European Commission [EC] failed to follow proper recruitment procedures, triggering the annulment of Rasi’s appointment.

Having been forced to remove Rasi from his post, EMA named Pott as acting director. Pott faces the task of implementing new clinical trial legislation, managing the ongoing dispute over data transparency and getting changes to medical device regulation underway. The fallout from disputes in the EC about the oversight of EMA and the resignation of the director-general for health could also affect the regulator. Pott has faced similar circumstances in the past. When Pott last served as acting executive director, he dealt with reports Lönngren was advising pharmaceutical companies, a request from a politician to fire an EMA expert, and a spat with the Nordic Cochrane Centre over the publication of clinical trial data, the Finnegan’s Take blog summarized in 2012. On that occasion, Pott held the post for one year. At this stage it is unclear how long his latest spell will last.

11/12/2014 EMA responds to European Ombudsman
11/24/2014 EMA releases practical guidance on access-to-documents requests

11/14/2014 European Medicines Agency Chief Unexpectedly Steps Down

 

We all know, that’s not what happens. The results are turned over to the corporate sponsor who analyze the results and use medical writers to produce the article. In many cases, the physicians and other scientists on the Author By-Line are primarily a ticket into a peer-reviewed journal, and have little if any input into the actual production of the article. And since the reader of the article can’t see any of the process that goes into the creation of what they’re reading, the data can be subtly manipulated to accentuate the positive and eliminate the negative. It not only can happen, it has happened in epidemic proportions – yielding enormous profits and more importantly has resulted in doctors prescribing many ineffective or sometimes harmful medications. The time for simply decrying this state of affairs has long passed. It’s time to put a stop to it, but that’s proving to be a very thorny task.

Every solution to this problem starts with Data Transparency. Unless science at large has access to every part of that top figure, the problem will persist. And the industry that stands to gain has mounted a sustained resistance at every point along the road. Their public arguments are commercially confident information and patient confidentiality, but that’s simply a smoke-screen for their real problem. Without the cover of darkness, many of the medications released in recent decades wouldn’t have made it to first base. There’s nothing scientific about the idea that new drugs are better, or that new drug discovery can proceed at a predictable pace. "A good man drug is hard to find. You often always get the other kind." – wouldn’t be a bad theme song for this industry.

Honoring Our Promise: Clinical Trial Data Sharing

NIH Director’s Blog

by Drs. Kathy L. Hudson and Francis S. Collins

November 19, 2014

[full text on-line]

When people enroll in clinical trials to test new drugs, devices, or other interventions, they’re often informed that such research may not benefit them directly. But they’re also told what’s learned in those clinical trials may help others, both now and in the future. To honor these participants’ selfless commitment to advancing biomedical science, researchers have an ethical obligation to share the results of clinical trials in a swift and transparent manner.

But that’s not the only reason why sharing data from clinical trials is so important. Prompt dissemination of clinical trial results is essential for guiding future research. Furthermore, resources can be wasted and people may even stand to be harmed if the results of clinical trials are not fully disclosed in a timely manner. Without access to complete information about previous clinical trials — including data that are negative or inconclusive, researchers may launch similar studies that put participants at needless risk or expose them to ineffective interventions. And, if conclusions are distorted by failure to report results, incomplete knowledge can eventually make its way into clinical guidelines and, thereby, affect the care of a great many patients. Unfortunately, the timely public reporting of results has not been consistent across the clinical trials enterprise. For example, a recent analysis of 400 U.S. clinical trials found that even four years after the trials had been completed, nearly 30% had failed to share results by publishing in a scientific journal or reporting in ClinicalTrials.gov, a public database maintained by NIH.

Today, the Department of Health and Human Services [HHS] proposed a rule to require public sharing of key results — the summary data — from certain clinical trials of drugs and devices regulated by the Food and Drug Administration [FDA]. While such a mandate has been in place for several years, the proposed rule aims to clarify the requirements. Summary data would include: baseline characteristics of participants, primary and secondary outcome results, and information about adverse events. With a few exceptions, such results must be submitted to ClinicalTrials.gov within one year of the time when the trial completes collection of primary outcome data. But we at NIH are proposing to go one step further to address this important issue. Today, NIH released a draft policy for public comment to apply these data reporting requirements to all interventional clinical trials that it funds. We are committed to working with NIH-supported researchers and institutions to ensure the new responsibilities in this proposed policy are understood and any unanticipated obstacles are removed.

What all this really comes down to is trust. Clinical trial participants trust that the data they provide will be used by biomedical science to advance the health of many. Researchers seek to add to the body of biomedical knowledge and can respect this commitment by promptly sharing clinical trial data. There is also the important matter of public trust. American taxpayers trust NIH to be a good steward of their investment — and one way we can do that is to ensure that results of all our clinical trials are shared with the worldwide scientific community in an open and efficient manner. Data sharing is essential to turn even more scientific discoveries into better health at an even faster pace!

Unfortunately, the clinicaltrials.gov results database isn’t comprehensive [see bring on the hoops! at least the ones that matter…]. But it’s a hell of a lot better than nothing, and this NIH proposal initiates something that has been woefully lacking – enforcement. Looking back through the history of all the many reforms attempting to keep this business of drug testing scientific and honest, it looks almost like a comedy of errors. I don’t think that’s right. Most of the reforms seem to me to be serious attempts at getting the drug testing on the right path. Two things have been missing. The first is obvious – enforcement. With clinicaltrials.gov, they had a very right idea, but there was essentially no enforcement. The drug companies and others just ignored the law. That’s the really important part of this move by the Dr. Collins [Director of the NIH] if he’s serious and follows through. The second thing is ongoing monitoring. This history has been written by many well-meaning congressmen, reformers, and agencies, but they haven’t stayed at it. Industry is always at it. So the crises pass and drug companies just keep on doing what they’ve been doing as soon as the dust settles. It’s time for a new clamor – enforcement and ongoing monitoring. Without those two things, it’s all just more empty promises…

UPDATE: This is the working link for comments: