1 Boring Old Man

^{In the days before television and other devices, some satirists used the comic strip for their commentaries – none more effectively than Walt Kelly who drew Pogo. Pogo possum and Kelly’s other anthropomorphized denizens of the Okefenokee Swamp delighted us with political satire and commentary on the human condition for a quarter century. There was only one character, Pup Dog, who remained on all fours as a playful puppy and only said "wurf." But there was a period, where he said, "Poltergeists make up the principal type of spontaneous material manifestation" – a nonsense Tautology that translates to "ghosts are ghosts."}

To be honest, these short term clinical trials don’t really need much writing by anyone at all. Some simple tables would do just fine: a list of the primary and secondary outcome variable defined before the study started with their results; the subjects’ demographics and drop-out rates; some comparative tables of adverse events; and a special table for severe adverse events. Write a few sentences at the end summarizing the conclusions. How their assertion that "In fact, the contributions and expertise of medical writers working with authors is associated with more complete reporting of the results of clinical trials and higher quality content" fits into that is unclear [and highly unlikely]. The notion of the hired-on ghostwriters and the hired-on KOLs working hand in hand to produce a value-added article is a fabulist scenario. Neither has seen the data or run the numbers, so the whole picture they’re painting in their response to Matheson is a fantasy. We have a few opened windows into the ghostwriting process via subpoenaed internal emails and documents from various lawsuits. The general pattern is for the ghostwriter to get some kind of summary document from the Sponsor to turn into a first draft. After it’s tweaked by the Sponsor, it’s cleared for the "authors" to take a look at – hardly the royal road to "higher quality content."

"ISMPP’s long-standing position is that “ghostwriting” – defined by Laine and Mulrow in 2005 as individuals who wrote the paper but are not acknowledged’ – is an unacceptable practice…"

"ISMPP fully supports the role of professional medical writers and the complete and transparent disclosure of their involvement in medical publications and the source of their funding."

"… My analysis shows, however, that modest transparency and small print disclosure, while better than nothing, paradoxically provides an apparatus for subtle misattribution, concealment and spin. My article discusses this as a cultural problem within medicine for which many stakeholders are responsible. It is important not to lay the blame at industry’s door alone. As Stretton rightly points out, it is journals that make authorship rules, and decide how disclosures should be presented to their readers. Table 2 of my article provides some useful suggestions to the editorial community."

"More importantly, however, while I applaud Stretton’s and Weigel’s commitment to transparency, I remind them that the publications trade remains unacceptably secretive. Numerous articles are produced for journal publication every year, scientific platforms and publications plans are developed, academics are recruited to participate as authors, trade writers draft manuscripts, and substantial payments pass from corporations to agencies, but little of this activity is in the public domain. Indeed, the process has been characterized as ‘ghost management’. Commercial secrecy has no place in an open scholarly discourse…"

This affirmation of continued commercial secrecy on these aspects of medical journal literature – made directly to the medical community itself, in a leading medical journal – will be of broad ethical and policy concern. The joint statement ends by claiming the trade has been “working towards” transparency and disclosure for 15 years. There is clearly a long road yet to travel…

12 September 2016: from Al Weigel – President and CEO, International Society for Medical Publication Professionals [ISMPP]

… ISMPP’s long-standing position is that “ghostwriting” – defined by Laine and Mulrow in 2005 as “individuals who wrote the paper but are not acknowledged” – is an unacceptable practice. ISMPP fully supports the role of professional medical writers and the complete and transparent disclosure of their involvement in medical publications and the source of their funding. In fact, the contributions and expertise of medical writers working with authors is associated with more complete reporting of the results of clinical trials and higher quality content.

Over more than a decade, disclosure of the role of medical writers [and their funding] in contributing to medical publications has progressed to become standard practice today. The involvement of medical writers, statisticians, and others are made fully transparent to journal editors and peer reviewers, and ultimately to the readers of the published literature, along with the authors’ disclosures and potential conflicts of interest. Through their interactions with authors, medical writers are important contributors to the timely and complete dissemination of clinical data in the medical literature…

15 September 2016: from Serina Stretton, Cindy Hamilton, Jackie Marchington, Art Gertel, Julia Donnelly – Global Alliance of Publication Professionals [GAPP]

… At the core of Matheson’s article are claims that there is no distinction between ghostwriters and professional medical writers, and that the pharmaceutical industry uses medical writers to insert commercial messages into the peer-reviewed literature. We completely agree with and support the International Society for Medical Publication Professionals [ISMPP] response to Matheson’s claims that there has been no “rebranding of ghostwriting” by industry and that rather, “there has been a positive evolution of transparency and completeness in medical publications reporting industry research.” As GAPP has stated consistently, professional medical writers are NOT ghostwriters because they ARE transparent about their involvement, are strictly prohibited from ghostwriting, and work within ethical publication guidelines that require authors to contribute to and control the content at every step of the publication process…

21 September 2016 from Alastair Matheson

21 September 2016 from Alastair Matheson

Weigel and Stretton both object to my article by emphasizing their trade’s commitment to “transparency”. My analysis shows, however, that modest transparency and small print disclosure, while better than nothing, paradoxically provides an apparatus for subtle misattribution, concealment and spin. My article discusses this as a cultural problem within medicine for which many stakeholders are responsible. It is important not to lay the blame at industry’s door alone. As Stretton rightly points out, it is journals that make authorship rules, and decide how disclosures should be presented to their readers…

Numerous articles are produced for journal publication every year, scientific platforms and publications plans are developed, academics are recruited to participate as authors, trade writers draft manuscripts, and substantial payments pass from corporations to agencies, but little of this activity is in the public domain. Indeed, the process has been characterized as ‘ghost management’. Commercial secrecy has no place in an open scholarly discourse. Since this literature has been placed within the public academic forum with the goal of informing treatment decisions, readers and their patients have a right to know exactly what commercial considerations were at work in its development, and who was paid by whom to create the material…

30 September 2016 from Alison M Rapley, President, European Medical Writers Association

The International Society for Medical Publication Professionals (ISMPP) and Global Alliance of Publication Professionals [GAPP] have already provided detailed responses to the issues raised in the article by Alastair Matheson. The American and European Medical Writers Associations [AMWA and EMWA] fully support these responses which were prepared by medical communications leaders who have been on the forefront of assessing and establishing ethical and robust professional standards. These standards included input from editors of first-tier peer-reviewed medical and scientific journals. There was no pharmaceutical industry review or input into these rapid responses. Clearly Dr Matheson’s interpretation of what constitutes ethical transparency differs from that of these major medical communications organizations representing thousands of professionals working around the globe, as well as differing from that of the International Committee of Medical Journal Editors [ICMJE] who represent more than 500 medical journals.

The undersigned organizations have been working towards transparency and disclosure for more than 15 years and invite all interested parties with a stake in the future of effective and ethical medical publications to tender constructive suggestions directly to them.

Alison Rapley – President, European Medical Writers Association
Brian Bass – Past President, American Medical Writers Association
Al Weigel – President and CEO, International Society for Medical Publication Professionals
Serina Stretton – Global Alliance of Publication Professionals

Trade associations’ joint statement on transparency in the commerical publications trade

British Medical Journal – Rapid Response

by Alastair Matheson

October 7, 2016

The debate following my article has culminated in a very rare, and unaccommodating, joint public statement on transparency by the three foremost trade associations of the commercial publications industry – the International Society for Medical Publication Professionals [ISMPP] and the European and American Medical Writers Associations [AMWA and EMWA].They have been joined in this statement by the Global Alliance of Public Professionals [GAPP], the most active advocacy group for the trade. In this statement, these groups have given their official response to a series of specific transparency requests which I made in order to clarify where the trade stood on secrecy and transparency in its development of medical journal articles. The trade chose to meet none of these requests, indicating its commitment to continued secrecy on these aspects of the medical publications business.

In particular, the trade did not agree to reveal any details of the commercial publications plans, scientific platforms, product positioning and key messages underpinning its past, and future, journal articles; nor did it agree to release details about its recruitment and use of “key opinion leaders”; nor details of intellectual property rights; nor any indication of how much money its companies receive from industry clients to plan and develop these articles. All this information is to be remain withheld from the readers of this literature and their patients. Most remarkably, the trade did not agree even to disclose exactly what it has published. It did not agree to provide simple lists of its published output; it did not agree to disclose any secret ghostwriting it may be aware of in the published journal literature; and it did not agree to encourage writers to disclose such articles, or to waive their confidentiality agreements if they do so.

This affirmation of continued commercial secrecy on these aspects of medical journal literature – made directly to the medical community itself, in a leading medical journal – will be of broad ethical and policy concern. The joint statement ends by claiming the trade has been “working towards” transparency and disclosure for 15 years. There is clearly a long road yet to travel…

So I was nosing around looking for something to keep me from perseverating endlessly about the NIH/ClinicalTrials.gov/FDA business and our Petition, and in my twitter feed, Dinah [Shrink Rap] had tweeted a New York Times article about the political affiliations of different medical specialties [Your Surgeon Is Probably a Republican, Your Psychiatrist Probably a Democrat]. Looking at it, I had a hunch of sorts, so I googled "medical specialty salary", and immediately got the Medscape Physician Compensation Report 2016. The lists had close to the same specialties, so I plotted all that were on both lists against each other [mean salaries versus political affiliation]. Voila` – data! Other than the outliers [Cardiologists and Family Practitioners], not bad.

Is there a which-came-first? the chicken or the egg relationship here? What does it mean? I can make up stuff, but I haven’t got a clue. I was just trying to distract myself from The Petition and from my wife’s leaving for a trip this afternoon to South America [via Miami now that Hurricane Matthew has moved up the coast]. But here’s the thing. It didn’t work. I wasn’t distracted like I planned. When I clicked on the spreadsheet trend line menu item, I didn’t bother to do the stats to see how well the line fit the points. Why? Because this is an Exploratory bit of fluff. I didn’t have a hypothesis to even test, just some playing around and had a hunch. And statistical testing is essentially meaningless when you’re just messing around with hunches and such. They’re for Hypothesis Testing under strictly defined conditions. So see, my mind is still on statistical testing and clinical trials – even when I’m horsing around.

As silly as my example is, it’s actually a notch above some of the sheenanigans that have gone on in the serious world of drug testing. In a number of these clinical trials, it’s obvious that somebody cheated – meaning they looked at the data after the study was done, or peeked at it through the blind while it was ongoing and selected outcomes that showed what they wanted to see. And that’s simply impossible to ever prove. So that’s the reason the a prori Protocol and Statistical Analysis Plan must be concretely certified before the study begins. It’s the only way to prevent that kind of cheating [outcome switching].

Likewise, one needs to see the actual results of the prespecified parameters and methods to evaluate whether the reported results match the reported conclusions. As much as this system has been abused, it’s hard for me to imagine leaving loopholes in place. The FDA is tasked with protecting and monitoring  the American formulary. Insuring the accuracy of the results of these clinical trials in terms of efficacy AND toxicity as they are reported in academic journals is near the top of the list.

EXECUTIVE SUMMARY

PURPOSE
This petition asks Congress to require the U.S. Food and Drug Administration (FDA) and the National Institutes of Health (NIH) to coordinate so as to prevent misreporting of clinical trials.

JUSTIFICATION
It is by now no secret that medical journals often publish biased reports of clinical trials funded by industry. These biased reports exaggerate benefits and minimize harms of new medical products (drugs and medical devices). Corporations succeed in this practice by sending different information and statistical analyses to the NIH than what they sent to the FDA. Medical journals, which rely on NIH data, have no way to detect these discrepancies. Both the FDA and the NIH know that this happens, but they do nothing, so the misleading claims escape regulation. We aim to close this loophole.

SPECIFIC STEPS TO RECONCILE FDA DATA AND NIH DATA

Trials Registration: Our petition first asks Congress to require coordination between FDA and NIH in the registration of clinical trials. Already, these must be pre-registered with the FDA and with the NIH (through the NIH public site called ClinicalTrials.gov). The second of those steps is often ignored or delayed. We ask Congress to require posting of the study protocol and detailed plan of statistical analysis with ClinicalTrials.gov at the time of registration with the FDA (current rules for the NIH site allow a delay of 1-3 years beyond the date of final data collection). The key elements of trials registration are to declare the a priori study protocol and the a priori statistical analysis plan before the study actually begins. That includes specification in advance of the primary and secondary outcome measures by which efficacy and safety will be assessed. Any other outcome measures must be clearly labeled as exploratory or non-protocol. The FDA then shall post a notice on ClinicalTrials.gov confirming or disconfirming that the a priori protocols and plans of analysis registered at both sites are identical.

Reporting Results: We also ask Congress to require timely publication of trials results on the NIH site and certification by the FDA that the information placed on the public NIH site agrees with the results that the FDA itself reviewed. Congress shall require that the FDA shall (i) post the FDA’s analyses on ClinicalTrials.gov as soon as the product is approved or disapproved for the requested indication; (ii) verify by notice whether corporate analyses reported on the NIH site are consistent with the a priori registered statistical analysis plan; (iii) verify by notice whether Results posted on ClinicalTrials.gov are concordant with Results determined by the FDA review; (iv) post on ClinicalTrials.gov a notice of any requested follow-up Phase 4 trial; (v) notify both the responsible party and ClinicalTrials.gov if the FDA determines that any corporate information placed on ClinicalTrials.gov conflicts with the data on file at the FDA; and (vi) notify both the responsible party and ClinicalTrials.gov if the FDA determines that any requested Phase 4 trial was not registered on ClinicalTrials.gov. Any publication or presentation or brochure or press release shall be required to display links to the trial’s registration on ClinicalTrials.gov and to any applicable FDA notices.

Expected Benefit: This petition requires both the FDA and NIH to meet their obligation to protect the public safety through genuine coordination of their joint oversight responsibilities. When FDA and NIH coordinate in these ways, then editors and reviewers at medical journals, and other stakeholders, can verify the fidelity of reported protocols and analyses. These provisions will allow stakeholders to determine whether any secondary analyses that use modified data sets or that address unplanned secondary questions have been properly identified.

These steps will prevent the widespread manipulation of in-house corporate statistical analyses that are the basis for misleading reports in the medical journals. Positive analyses based on the a priori protocol and statistical analysis plan may be clinically actionable, as determined by the FDA. However, positive in-house corporate statistical analyses based on modified outcome measures or protocol changes cannot be regarded as clinically actionable, even though that is implied in medical journal reports, e.g., for off-label us es and unapproved patient groups such as children. These changes will for the first time allow stakeholders to recognize such claims for what they are.

Perhaps, rather than talk about what the NIH and FDA propose doing about it, we should frame the problem that needs fixing. Because of the PHARMA Sponsors’ keeping clinical trial data secret [proprietary, intellectual property] and the FDA, the only entity with access, we are only privy to the published journal articles for our information about clinical trials. And it is increasingly apparent that there has been widespread corruption in the public reporting – leaning towards exaggerated efficacy and minimization of harms. While it’s hard to prove because it happens behind closed doors, a common tool of distortion involves outcome switching – changing reported outcome parameters to fit the results. For this and other more scientific reasons, the outcome parameters and methods of analysis must be declared before the trial begins.

• … the reader can be assured that the outcome parameters weren’t changed based on the data itself [Hypothesis After Results Known – HARK]
• … then the reader sees the RESULTS of those prespecified variables directly
  
• … so there’s no question about the outcome of the trial.
  

How could we be sure that the a priori declaration of parameters and methods is accurate? Ask the FDA to certify their accuracy. In most cases, they already have the documents as part of an FDA registration. How could we know that the resulrs posted are accurate? Ask the FDA to certify that they match those submitted to the FDA. They are the only agency with access to the data itself, and have evaluated it as part of their approval process.

But that’s not what the NIH/ClinicalTrials.gov/FDA did [see what to do? the final rule?…]. The NIH and ClinicalTrials.gov wrote the final rule, which is essentially what was in place before except they clarified a few ambiguities and promised to enforce it this time around. The FDA was supportive but changed nothing. It’s going to take direct legislation to get changes like the ones suggested above in place – mandated by Congress. Those are the exact changes that are in our petition [Stop False Reporting of Drug Benefits & Harms by Making FDA & NIH Work Together]. Please take a look and sign it. 

1. Toward a New Era of Trust and Transparency in Clinical Trials
2. Trial Reporting in ClinicalTrials.gov — The Final Rule
3. New federal rules target woeful public reporting of clinical trial results
4. HHS Issues New Rules To Open Up Data From Clinical Trials

From the STAT article [New federal rules target woeful public reporting of clinical trial results]:

• Federal officials said last year that they wouldn’t penalize offenders before clarifying the reporting rules. Now that this is happening, “I’m expecting a flood of trials to get registered,” FDA Commissioner Robert Califf told reporters during a conference call. “It would be pretty hard to hide that you are doing a clinical trial or hide the result. … I’m very optimistic about this.”
• Yet not a single researcher or trial sponsor has been fined or penalized, STAT reported — though the Food and Drug Administration had the authority to fine violators more than an aggregate $25 billion since the law went into force in 2008.
• Neither agency will add such staff, according to Califf, whose agency oversees private sector reporting, and NIH Director Francis Collins, whose agency is responsible for enforcement regarding NIH grant recipients as well as NIH staff scientists.
• Califf said enforcement instead would be folded into the FDA’s existing bioresearch monitoring program, which collects information related to clinical trials during company inspections.
• “Typically, when the FDA believes there may be a violation of the law, it sends a warning letter” for voluntary correction, Califf said. He expects this method to handle most problems, and promised that the public will have “a good window of what’s going on” in compliance actions.

In the NPR article [HHS Issues New Rules To Open Up Data From Clinical Trials],

• "This has been a very opaque world up until to now," Food and Drug Commissioner Robert Califf told reporters during an embargoed phone conference Thursday. "These are tremendous changes."
• For studies that are regulated by the FDA, companies can face fines of $10,000 a day if they don’t comply with the existing rules. Those fines have not been imposed, however, and the FDA will not have additional funding to hire enforcement staff, Califf said. "I really believe that it won’t take much to get people to comply with this once they realize how serious this is."

And I wasn’t in love with this one either:

• Both agencies will automate compliance checks to ensure trials are properly registered and results reported, and contact institutions as needed to provide all the data required to bring their trials into compliance with the law.

And in spite of being impressed that the NIH/ClinicalTrials.gov final rule shows signs of some real effort and investigation, I question their solutions. There are two points in the life cycle of a clinical trial where data is entered into ClinicalTrials.gov – Registration and Results:

• Registration [the final rule]:
  when – "Submission: Within 21 days after enrollment of the first trial participant. Posting: Generally, within 30 days after submission…"
  what – "Descriptive information about the trial: e.g., brief title, study design, primary outcome measure information…"
• Results [the final rule]:
  when -"Submission: Standard deadline: Within 12 months after the date of final data collection for the prespecified primary outcome measures (primary completion date)…"
  what – "Outcomes and statistical analyses for each primary and secondary outcome measure by treatment group or comparison group, including results of scientifically appropriate statistical analyses performed on these outcomes, if any. Adverse event information: Tables of all anticipated and unanticipated serious adverse events and other adverse events that exceed a 5% frequency threshold within any group"

• Registration: Preregistration of the Primary and Secondary Outcome Parameters and the Methods by which they will be analyzed is an essential ingredient of a scientifically conducted clinical trial. Changing outcomes after the study is underway has been a major method used to deceitfully jury-rig the results [see ]. Ergo any effective reform must insure that a certified copy of that a priori Protocol and Statistical Analysis Plan is filed before the trial begins. Filing those things with the Results in case there are amendments is also fine, but does nothing to reassure us that these variables haven’t been changed. These documents have just been used in the submission to the Institutional Review Board, so they are at hand. Why not file them with the registration and post them on the public face sheet on ClinicalTrials.gov? To do otherwise is to start off with a huge loophole that has been chronically exploited.
• Results: While the Sponsors [PHARMA] have succeeded in holding on to their claima of keeping the raw data proprietary [secret], they have no such claim on the results. After all, it’s what they themselves publish in the journal articles they generate. The Results Database on ClinicalTrials.gov should have the results of the predefined Primary and Secondary Outcome Parameters clearly labeled. Any other Outcomes should be labeled ‘exploratory’ or ‘non-Protocol’. In addition, since they have already been calculated for submission, there’s no reason to delay posting them. Posting results at the time of submission to the FDA is essential. Why? So Journal editors, peer reviewers, you and me can see them. And the whole point of this enterprise is to deal with the widespread corruption in the reporting of clinical trials in our literature!

Tracking Hurricanes is something of a spectator sport around here, even though we’re mostly bulletproof in North Georgia. But in a lifetime of Hurricane watching, I’ve never seen a prediction like this one – Here we go loop-de-loop…

 

Independent Drug Testing to Ensure Drug Safety and Efficacy

by Marc A. Rodwin

Journal of Health Care Law & Policy. 2015 18:45-84.

[full text on-line]

 

A. The Origins of Contemporary Pharmaceutical Regulation

Before examining the oversight of clinical trials, let us briefly review the evolution of the pharmaceutical industry over the last century. In the beginning of the twentieth century, the drug market was premised on the doctrine of laissez-faire. Manufacturers did not have to test their drugs or disclose the ingredients, could make any therapeutic claim, and could sell any product directly to consumers.

Reformers and muckrakers—supported by the American Medical Association [“AMA”]—spearheaded the fight for federal drug regulations. In 1906. Congress passed the Pure Food and Drug Act, which required manufacturers to disclose therapeutic ingredients on the drug label, and prohibited the sale of adulterated, misbranded, or deleterious products. The law presumed that, with accurate labeling, individuals could safely choose drugs. Advertising of therapeutic claims remained unregulated until the Shirley amendments in 1912 prohibited false and fraudulent statements regarding the curative or therapeutic effect of drugs."

Industry opposition blocked enactment of the Roosevelt administration’s 1933 bill to regulate drugs until a scandal in 1937. In order to improve the flavor of a sulfa-based drug called sulfanilamide, the Massengill Company added a chemical that was toxic, causing the rapid death of 106 people who had ingested the drug. Congress then passed the Food. Drug, and Cosmetic Act of 1938 [“FDCA”]. which required drug firms to seek FDA permission to market drugs, and which allowed the FDA 60 days to deny authorization if it found that the drug was dangerous or improperly labeled.

Manufacturers then had incentives to conduct research and to evaluate their products. The marketing of Thalidomide led to the birth of children with severe deformations in multiple countries, and created pressure for stronger regulation. The 1962 amendments to the FDCA prohibited marketing of drugs unless the FDA granted approval, and the amendments removed the 60 day deadline for FDA review of new drugs. The amendments required drug sponsors to demonstrate that drugs are effective—not only safe—for a designated use. It also authorizes the FDA to withdraw its approval for drugs already on the market based on new evidence. Manufacturers are required to track drug distribution to facilitate recalls of unsafe products, and to follow FDA standards for good manufacturing practices. The law restricts promotion of drugs to therapeutic uses approved by the FDA. Promotional materials must note risks, as well as benefits, and summarize side effects and contraindications. The FDA specifies what information the label must include, and labels must state the generic name, as well as the brand name.

In 1970, the FDA promulgated regulations that set standards for the evidence that manufacturers would have to submit in order to demonstrate that new drugs were safe and effective. Since then, testing of drugs follow set stages. After researchers have identified a potentially therapeutic molecule, they test its effects in laboratories on chemicals, cells, or tissues. The FDA then requires firms to test its drugs for toxicity on animals. Drug candidates that have not been ruled out due to toxicity or lack of efficacy can then be tested on humans in three phases. In Phase I. researchers test the drug on a small number of human subjects only to determine whether it is toxic in humans, and if so, at what doses. Phase II testing consists of a clinical trial in a larger group of patients in order to measure its benefits and risks. Drugs that are not highly toxic are tested in Phase III clinical trials on a large number of human research subjects, and researchers then compare its effect with a control group. Typically, the control group uses a placebo or an alternative therapy. Human subjects are randomly assigned to either the test group or the control group. It is a double blind study, which means that the medication must be coded so that neither the physician who administers the drug, nor the individual taking the drug, knows which individuals receive the test drug and which individuals receive the placebo [or the standard therapy to which it is compared] until the code is broken after collection of data. To counter the risk of fraud or unreliable studies, regulations establish standards for research methods, record keeping, and data reporting. The FDA also inspects toxicological laboratories and facilities that conduct clinical trials in order to monitor compliance.

B. Options for Control of Clinical Trials

There are six options for addressing conflicts of interest in clinical trials, which are displayed in Table 1 below. At one extreme, the drug sponsor has complete control over clinical trials; at the other extreme, the federal government conducts the clinical trials. Between these two poles are four strategies that can be used individually or combined. The FDA relies mainly on the second strategy, which has been supplemented in recent years by the fourth strategy…

Drug manufacturers face a fundamental conflict of interest. Pursuit of profit compromises drug manufacturers" impartial assessment of the risks and benefit of their drugs. Their biased evaluation can corrupt public knowledge of drugs, lead to marketing unsafe and/or ineffective drugs, and undermine rational physician prescribing. Over the last century, federal regulation has mitigated, but not eliminated, this problem…

Right now, we’re operating in what Rodwin calls "the fourth strategy" – regulation. And it hasn’t gone so very well. At least in psychiatry, we’ve had 25 years of grossly exaggerated indications, efficacy reports, and safety claims. And even now that these medications’ failings are more publicly known, mental health care policy is still being formulated with these meds as the central strategy [eg collaborative care], metastacizing into the domain of primary care – a particularly shaky idea in my [and many other’s] opinion.

I’ve heard from several people that they’re not sure exactly what we’re asking Congress to do. Our narrative is long because it coveres many bases. Here’s the short version. We want Congress to mandate that the FDA talk to us directly through clinicaltrials.gov about the clinical trials of FDA regulated drugs. The drug and device manufacturers have created a whole fabulist industry that fills our journals with articles about clinical trials that are often/usually inaccurate and used as marketing tools. Meanwhile the FDA, the only kid on the block that can actually see the data in the raw, watches all of this happening but does nothing. The public interface designed to give us an alternative to these journal articles, the NIH’s clinicaltrials.gov, has withered from disuse atrophy because nobody populates it on time [if at all] or checks up on it.

We’re proposing that Congress give us an alternative to the jury-rigged articles published by industry in our journals. All the pieces to create that alternative system are already in existence. The NIH’s clinicaltrials.gov is a well designed system for telling us what we need to know. The FDA has access to all of the information about the clinical trials on FDA regulated drugs, submitted in applications for approval. If it’s not all there, they can suspend action until they get it. So we are asking Congress to make the NIH clinicaltrials.gov the official interface between the FDA and the physicians/patients who need to know about these clinical trials.

• Create a Protocol that  defines the target population, the intervention(s) to be tested, and define the PRIMARY and SECONDARY OUTCOME  PARAMETERS and how they will be analyzed BEFORE the study begins.
• Then do the study.
• Perform the a priori defined analyses on the a priori defined PRIMARY and SECONDARY OUTCOME PARAMETERS [a priori means BEFORE anyone gives the first subject the first pill].
• Display the RESULTS.

We want the FDA to actively check that the original REGISTRATION on clinicaltrials.gov is filed before the study starts, that the PRIMARY and SECONDARY OUTCOME PARAMETERS and how they will be analyzed are clearly specified, and that the version on clinicaltrials.gov is the same as the version filed with the FDA [NDA and PMA trials]. We want the FDA to post a notice on clinicaltrials.gov that this has been done.

We want the same thing with the RESULTS. We want the FDA to actively check that the results are posted on clinicaltrials.gov for every trial submitted to the FDA at the time of submission. We want the FDA to insure that those results on clinicaltrials.gov are the same as those in the FDA analysis [the a priori defined analysis of the a priori defined the PRIMARY and SECONDARY OUTCOME PARAMETERS]. We want the FDA to post a notice on clinicaltrials.gov that this has been done.

The sponsors of these clinical trials have so far succeeded in their bizarre claim that the clinical trial data is proprietary. But they can’t claim that that’s true of their version of the results. These are FDA regulated drugs and those results are part of the regulatory process. While the FDA has no jurisdiction over journal articles, if the articles misrepresent the FDA certified results or include other parameters or analyses without clearly annotating them as non-protocol results, the FDA should have the injunction to act [false advertising].

There’s more, but that’s enough. You get the drift. If the sponsors of these trials and the journals they publish in can’t give us accurate scientific reports on these crucial clinical trials, we are petitionong Congress to mandate that the FDA provide  it to us – by law. Like many of you, we’re as…

… mad as hell and we’re not going to take it anymore!