Princess Health and Transparency International Reports on Massive Corruption in the Pharmaceutical Sector - Media Hardly Notices. Princessiccia

Princess Health and Transparency International Reports on Massive Corruption in the Pharmaceutical Sector - Media Hardly Notices. Princessiccia

anechoic effect deception health care corruption manipulating clinical research marketing pharmaceuticals suppression of medical research Transparency International

Gusty 07:28 Add Comment

Health Care Corruption as a Taboo Topic

Transparency International (TI) defines corruption as

Abuse of entrusted power for private gain

In 2006, TI published a report on health care corruption, which asserted that corruption is widespread throughout the world, serious, and causes severe harm to patients and society.

the scale of corruption is vast in both rich and poor countries.

Also,

Corruption might mean the difference between life and death for those in need of urgent care. It is invariably the poor in society who are affected most by corruption because they often cannot afford bribes or private health care. But corruption in the richest parts of the world also has its costs.

The report did not get much attention.  Since then, health care corruption has been nearly a taboo topic in the US.  When health care corruption is discussed in English speaking developed countries, it is almost always in terms of a problem that affects benighted less developed countries.  On Health Care Renewal, we have repeatedly asserted that health care corruption is a big problem in all countries, including the US, but the topic remains anechoic.

Yet somehow, a substantial minority of US citizens, 43%, seemed to believe that corruption is an important problem in US health care, according to a TI survey published in 2013 (look here).  But that survey was largely ignored in the media and health care and medical scholarly literature in the developed world, and when it was discussed, it was again in terms of results in less developed countries.  Health Care Renewal was practically the only source of coverage in the US of the survey's results.

Transparency International's New Report on Corruption in the Pharmaceutical Sector

Now Transparency International (TI) has tried, and Health Care Reenewal will try again.  In June, 2016 Transparency International published a new report entittled

Corruption in the Pharmaceutical Sector

The report's executive summary states:

Within the health sector, pharmaceuticals stands out as sub-sector that is particularly prone to corruption. There are abundant examples globally that display how corruption in the pharmaceutical sector endangers positive health outcomes.

In my humble opinion, the report is particularly significant in that it classifies as corrupt various kinds of activities that occur within the pharmaceutical sector (and also in other parts of health care) which are often discussed publicly as anything from standard operating procedure through unfortunate errors to unethical behavior. These include many activities which we have frequently discussed on Health Care Renewal. For example,

Manipulation of Clinical Research

We have frequently discussed how pharmaceutical companies, and biotechnology, medical device, and other health care companies and organizations, may manipulate clinical research to enhance the likelihood that is results will favor their products and marketing goals, even if the results are biased, inaccurate, could mislead physicians and patients, and ultimately harm patients.  The TI report included: 

As pharmaceutical companies rely on gaining market entry in order to recoup R&D costs, when there is a lack of oversight in clinical trial data publication a conflict of interest exists in which a pharmaceutical company may have an incentive to manipulate clinical trial data. When clinical trial data is manipulated medical literature can become biased with positive findings fabricated, positive findings exaggerated or negative results hidden. This can result in inadequate prescribing patterns because HCPs rely on clinical trial data to make decisions on which medicines to use to treat patients.

Suppression of Clinical Research

We have frequently discussed how health care organizations (as above) may outright suppress clinical research when the results fail to support their interests.  The TI report included:

Transparency and access to information through mandatory clinical trial registration, sanctions for not registering results or providing clinical trial information, and the publication of both positive and negative results are commonly discussed as helpful tools to curb corruption. With the European Medicines Agency (EMA) as a notable positive exception, public agencies and authorities do not require R&D-based pharmaceutical companies to make their raw data publicly available, making it impossible to verify whether the reported results are accurate. Based on laws and regulations clinical trial data is considered to be proprietary information, which allows pharmaceutical companies to conceal important data from the public domain.

Manipulation of the Dissemination of Clinical Research

We have frequently discussed how health care organizations may manipulate the dissemination of clinical research, through various forms of publications, presentations, courses, media summaries, etc, to favor their products and marketing goals, even if the results are misleading and could harm patients.  For example, a while back we discussed the problem of "ghost-written" articles appearing in scholarly journals. The TI report included:

The practice of ghostwriting is also a risk with clinical trials. Ghostwriting involves the writing of clinical trial publications by industry and then having a highly esteemed researcher pass these findings off as their own without disclosing their actual involvement with the authorship of the article. It is a common practice, particularly in industry led trials. Ghostwriting is done to increase the prestige and reputation of the findings, while simultaneously researchers are able to improve their reputation, which can lead to promotions. Clearly this practice can result in inaccurate results being published.

Deceptive Marketing

We have frequently discussed how marketing of pharmaceuticals (and nearly everything else in health care) may be deceptive, favoring companies' products and services, but again misleading health care professionals and patients, and ultimately risking patient harm.  In the extreme, pharmaceutical companies (and other health care organizations) may resort to bribes or kickbacks.  The TI report included:

There are several methods for a corrupt pharmaceutical company to unethically market its medicines. At its most simple a pharmaceutical company can bribe a HCP directly with payments so its medicines are more likely to be prescribed. More abstrusely individuals may include a pharmaceutical company�s medicine on the national list that is reimbursed by public funds, in return for an indirect bribe by being sent to inappropriate holiday destinations for lavish conferences.

Corrupt marketing practices also include pharmaceutical companies providing misleading information regarding the safety and efficacy of a medicine to influence doctors� prescribing habits and encouraging off-label, unlicensed use to increase sales.

Other Topics

Finally, the report mentions such issues as the revolving door, regulatory capture, etc, etc, etc

A Striking, and Strikingly Anechoic Report

Again, while the report summarizes information that is likely familiar to most Health Care Renewal readers, what is striking is that it describes manipulation of clinical research, suppression of clinical research, manipulation of dissemination of clinical research, and deceptive marketing as corruption.  That is a sentiment rarely heard in the US, and one that appears nearly taboo.  

Demonstrating the strength of the taboo, this striking report has gotten almost no attention in the media or scholarly medical and health care literature in the developed English-speaking countries.  Let me note the important exceptions, however.

I learned of the report from a brief news item from the BMJ, the prestigious UK journal that seems most at the forefront of championing the integrity of medical and health care research.(1)  The only substantial news article I could find on the report was also from the UK, in the Independent.  Its sub-title is worth repeating:

Transparency International says corruption is making a few rich and wrecking the health of some of the world's poorest people

Also, there were brief articles in Reuters, and in (web-only) FiercePharma.  That is about it so far.

The report itself suggests why it has been so anechoic, just like nearly every other attempt to expose health care corruption to public discussion.  Essentially, there is so much money to be made through pharmaceutical (and by implication, other health care corruption) that the corrupt have the money, power, and resources to protect their wealth accumulation by keeping it obscure.  In the TI Report itself,

However, strong control over key processes combined with huge resources and big profits to be made make the pharmaceutical industry particularly vulnerable to corruption. Pharmaceutical companies have the opportunity to use their influence and resources to exploit weak governance structures and divert policy and institutions away from public health objectives and towards their own profit maximising interests.

Keep in mind that the money made from corruption does not just go to innocent peoples' retirement funds that are invested in pharmaceutical stocks.  It predominantly goes to top corporate executives and managers, and their cronies who preside over the corrupt practices.


I might as well repeat myself once again.  As I wrote in 2015,

If we are not willing to even talk about health care corruption, how will we ever challenge it? 

So to repeat an ending to one of my previous posts on health care corruption....  if we really want to reform health care, in the little time we may have before our health care bubble bursts, we will need to take strong action against health care corruption.  Such action will really disturb the insiders within large health care organizations who have gotten rich from their organizations' misbehavior, and thus taking such action will require some courage.  Yet such action cannot begin until we acknowledge and freely discuss the problem.  The first step against health care corruption is to be able to say or write the words, health care corruption.

Reference

1.  Torjesen I.  Group calls for more to be done to tackle corruption in the pharmaceutical industry. BMJ 2016;353:i3099. Link here.

Princess Health and Pfizer's Latest International Pfiascos - Charges of Anti-Competitive Practices, Inflated Prices, Deception and Secrecy. Princessiccia

Princess Health and Pfizer's Latest International Pfiascos - Charges of Anti-Competitive Practices, Inflated Prices, Deception and Secrecy. Princessiccia

adverse effects antitrust deception executive compensation health care prices legal settlements marketing Pfizer suppression of medical research vaccines

Gusty 13:43 Add Comment

Many big health care organizations seem to just be unable to keep out of trouble, and the bigger they are, the more kinds of trouble.  Pfizer Inc, considered to be one of the world's largest pharmaceutical companies, has supplied us with plenty of stories.  Enough new stories about Pfizer have accumulated since last year to do a roundup.   

Presented in chronological order....

Italy Demands Damages from Pfizer for Anti-Trust Violations

This story came out in May, 2014, via Reuters,

Italy said on Wednesday it was seeking more than a billion euros in damages from multinational drug companies following a ruling by the country's antitrust authority that their policies had been detrimental to Italy's national health service.

The health ministry said in a statement it was requesting a total 1.2 billion euros ($1.6 billion) from Novartis and Roche for the damages incurred in 2012-2014, and was requesting 14 million euros from Pfizer.

It cited several recent antitrust rulings that the companies' repeated anti-competitive actions had caused the national health service 'considerable damage'.

The specific charges against Pfizer were:

Italy's state council, the highest administrative court, in February ruled that Pfizer had abused its dominant position relating to the glaucoma drug Xalatan 'with a clear and persistent intention to suppress competition'.

At least in English language news sources, I have not seen how this turned out, but note that this was apparently an administrative court finding, not just a prosecutor's allegation.

Pfizer Accused of Overcharging for Pediatric Vaccines

This appeared in January, 2015, here via Ed Silverman's PharmaLot blog (when it was affiliated with the Wall Street Journal),

In a bid to widen access to vaccines, Doctors Without Borders is calling on Pfizer and GlaxoSmithKline to lower the prices for their pneumococcal vaccines to $5 per child in developing countries. The non-profit claims the drug makers are 'overcharging' donors and developing countries for vaccines that 'already earn them billions of dollars in wealthy countries.'

The non-profit, which regularly advocates for lower prices for medicines, maintains that, in general, the price to vaccinate a child against several diseases is now a 'colossal' 68 times more expensive than in 2001. In a new report, Doctors Without Borders attributes 45% of that increased cost to the price tags for pneumococcal vaccines sold by the drug makers. Pneumococcal disease, by the way, kills about 1 million children per year, mostly in poor and developing nations.

Think about the children.

The non-profit maintains that the current price tag makes it difficult to supply the vaccine to large numbers of children, and the drug makers have already received $1 billion in incentives to manufacturer the vaccine for developing countries. 'We think it�s time for Glaxo and Pfizer to do their part to make vaccines more affordable for countries in the long term, because the discounts the companies are offering today are just not good enough,' says Malpani in a statement.

Moreover, Doctors Without Borders warns that pricing may eventually make it harder for a growing number of middle-income countries to afford vaccines. Over time, some of these countries will eventually �graduate� from the subsidized vaccine pricing established by Gavi and, when that happens, Doctors Without Borders estimates costs may rise up to six times what is the countries pay today.

The post included a statement from Pfizer about how hard it is to manufacture the vaccine, and an update to the post included a statement from Pfizer that it was already selling its pneumococcal vaccine, Prevenar 13, below cost to GAVI, which buys up vaccines and provides them to poor countries. A week later, again via (the old version of) PharmaLot, Pfizer announced an additional 6% price cut. Furthermore, Bill Gates, whose foundation supports GAVI, insisted that cutting vaccine prices would discourage pharmaceutical companies from investing in vaccine research and supplying products to poor countries, according to the Guardian.

However, neither Pfizer nor Mr Gates acknowledged how much money Pfizer already is making from Prevenar in developed countries, amounts which likely do far more than offset any losses in poorer countries. Specifically, in July, 2015 FierceVaccines reported that

The world's biggest vaccine by sales--Prevnar 13--just keeps getting bigger. And in doing so, the shot helped Pfizer notch 44% vaccines growth for the second quarter as the unit saw sales grow from $1.09 billion in last year's Q2 to $1.58 billion during the period this year.

For the quarter, the superstar pneumococcal disease-blocker notched a U.S. sales increase of 87% versus the same period last year, a jump Pfizer CEO Ian Read attributed to 'continued strong uptake' in U.S. adults.

Also,

Prevnar 13, which reeled in $4.29 billion in sales last year, is expected to grow to $5.83 billion in 2020 and remain atop the vaccines sales charts.

And,

The company is also working 'country by country' to broaden the vaccine's reach in G7 countries....

So there seems to be some evidence in support of the Doctors Without Borders claim that Pfizer could easily afford some small losses selling vaccines for use by poor children in less developed countries while it makes billions of dollars from vaccine sales in developed countries.  


Pfizer Settles Shareholder Suit for $400M

This settlement was just the latest that has resulted from allegations of illegal drug marketing by Pfizer.  As reported again by the redoubtable Ed Silverman in the old version of PharmaLot,

Pfizer has reached an agreement in principle to pay $400 million to settle a class-action securities lawsuit that alleged the drug maker illegally marketed several medicines and, subsequently, caused investors to lose money, according to a filing with the U.S. Securities and Exchange Commission.

The lawsuit alleged that, between January 2006 and January 2009, Pfizer marketed several drugs on an off-label basis. The medicines included the Bextra painkiller that was withdrawn from the market in 2005; the Geodon antipsychotic; the Zyvox antibiotic and the Lyrica epilepsy treatment.

The lawsuit, which was filed in federal court in 2010, alleged that the sales boost the drug maker received from the marketing prompted Pfizer executives to make 'false and misleading statements about Pfizer�s financial performance and sales practices [that] caused Pfizer stock to trade at artificially inflated prices.'

This settlement followed an even larger one back in 2009 when,

the drug maker revealed plans to pay $2.3 billion to resolve criminal and civil allegations that these drugs were marketed illegally.

We discussed that settlement in 2009 here, here, and here.  Note that the 2009 settlement included a guilty plea to a criminal charge (albeit to a misdemeanor), and was of allegations including paying kickbacks to doctors for use of Pfizer drugs.  So this additional settlement of deceiving investors just ices that cake. 

UK Competition and Markets Authority Stated Pfizer Abused Market Dominance

This story appeared in August, 2015, via the Telegraph,

The Competition and Markets Authority (CMA) has issued a statement of objections alleging the companies breached UK and EU law by raising the prices they charged for phenytoin sodium sold to the NHS.

In particular,

The CMA says that for years industry giant Pfizer, which is listed in the US, and Flynn, a Stevenage-based company, between them sold the drug at a price up to 27 times higher than it had been previously priced.

Before September 2012, Pfizer manufactured and sold phenytoin sodium capsules to UK wholesalers and pharmacies under the brand name Epanutin.

Pfizer then sold the UK distribution rights for Epanutin to Flynn, which 'de-branded' the drug and started selling its version in September 2012. Pfizer continued to manufacture the drug, which it sold to Flynn at prices the CMA says were 'significantly higher' than those at which it had previously sold Epanutin.

The CMA claims Pfizer sold the drug at between 8 and 17 times its historic prices to Flynn, which then sold on phenytoin sodium at between 25 to 27 times more than the prices previously charged by Pfizer.

Before Flynn bought the rights for Epanutin, the NHS spent about �2.3m on phenytoin sodium capsules a year, according to the CMA. After the deal this spend rose to just over �50m in 2013 and more than �40m in 2014.

While the CMA findings were apparently "provisional," but the agency has the power to find that the law has been breached and "has the power to fine then up to 10pc of their global annual turnover - last year Pfizer had revenue of almost $50bn."  So this is the second government finding of anti-competitive behavior by Pfizer in a little over one year.

Pfizer Resists AllTrials Calls for Transparency

Late in August, 2014, per the Guardian,

Pfizer, one of the world�s largest pharmaceutical groups, has said it will resist demands from investors and transparency campaigners that it disclose results from all historical drug trials.

We have been discussing how pharmaceutical, biotechnology, and device companies have manipulated the clinical trials they sponsor to increase the likelihood that the results make their products look good, and may suppress trials whose results cannot be made to look good enough. This clinical research suppression and manipulation can lead to poor clinical decisions, may harm patients, and abuses the trust of patients who volunteer to participate in clinical research. This situation has led to the AllTrials campaign to make clinical research transparent (look here). However,

Pfizer said it had a 'longstanding commitment to clinical trial transparency' and it already published data for trials from 2007. Requests for earlier data are considered on an individual basis. But it added: 'We don�t believe that further investment beyond this would offer value to patients, health services or to our shareholders.'

This despite arguments above about the harms of research suppression.  Given how much money Pfizer has spent on lawsuits, including one above about allegations of its management's deception of shareholders, one might think it would be worth it for management to make a little investment in transparency.

Pfizer Found to Have Withheld Reports of Adverse Drug Events in Japan

Finally, reported in September, 2015 by in-PharmaTechnologist.com,

Pfizer failed to report hundreds of serious adverse drug reactions (ADRs) in the required timeframes according to Japan�s Ministry of Health, Labor and Welfare (MHLW) which has issued the US firm with a business improvement order. 

That website has copy protection so I cannot quote further, but the order involved 11 drugs, including Enbrel and Lyrica.  So here is yet another example of a government agency finding that Pfizer was less than transparent, if not overtly deceptive.

Summary

So in a little more than a year, Pfizer has been accused of anti-competitive practices raising drug costs in Italy, excess pricing of vaccines for use by poor children in undeveloped countries, deceiving its own investors about illegal marketing activities in the US, abuse of market dominance leading to excessive drug costs in the UK, stonewalling clinical trial transparency measures globally, and failing to disclose adverse drug effects in a timely manner in Japan.  This is on top of an already impressive record of misbehavior (See our summary of Pfizer mischief at the end of the post.)

However, as seems usual these days, no one at Pfizer who might have authorized, directed or implemented any of this bad behavior has ever seemingly paid any sort of penalty for it.  Instead, while this was going on, the top leadership of Pfizer just gets richer faster and faster.  In fact, in March, 2015, the Wall Street Journal reported the current Pfizer CEO's total compensation in 2014,

Pfizer Inc. said Thursday that Chief Executive Ian Read�s total compensation rose 23% last year, lifted by an increase in pension value that offset a reduced annual bonus and equity award.

Furthermore,

Mr. Read�s 2014 pay package totaled $23.3 million. The board raised the CEO�s salary to $1.83 million from $1.79 million but decreased his annual bonus by $400,000 and his equity award by nearly $1 million despite concluding that Mr. Read�s leadership during the year was 'outstanding.'

[Even though] Over the course of 2014, shares in the New York-based pharmaceutical company gained about 2% amid a 4% decrease in revenue.

It is not obvious that the rise in CEO pay is even remotely correlated to any rise in share-holder value.  Moreover, there seems to be a total disconnect between the rewards given the CEO and the ethical record of the company he leads, especially since Pfizer, which calls itself "one of the world's premier pharmaceutical" corporations, announces its aspirations thus,

we at Pfizer are committed to applying science and our global resources to improve health and well-being at every stage of life. We strive to provide access to safe, effective and affordable medicines and related health care services to the people who need them.

Never mind all those pesky allegations of overpricing, anti-competitive practices, deception and opaqueness, and never mind that current executives are becoming exceedingly risk in part from the continuation of such practices.  So it seems the board of Pfizer will just continue handing its executives piles of money, despite, or for all I know, because of the company's continuing bad behavior.  Given these incentives, is it any wonder that the bad behavior continues?  Pfizer seems to be just another example - albeit a big one - of how health care is dominated by an oligarchy of unaccountable leaders who continue to demonstrate their impunity hidden by aspirational but hollow public relations and marketing.

Of course, it is doubtful such bad behavior would continue if there risks of external penalties, e.g., from law enforcement.  But there never seem to be any.

In the past, US law enforcement authorities have announced they would use the responsible corporate officer doctrine, a legally tested rationale for prosecuting corporate managers for bad behavior by those who report to them (e.g., in 2010, look here),  But it seems they have never done so, at least in cases involving large health care organizations.  Last week, the US Department of Justice announced it would start going after executives of companies that misbehave, and would press the companies to give up the name of responsible executives in exchange for more lenient treatment of the companies themselves (e.g., see this report in the NY Times).  Meanwhile, however, the march of legal settlements for bad behavior in health care continues, absent any penalties for organizational leaders who might have authorized or directed it, much less for those who simply put incentives in place to foster bad behavior while looking away from what those incentives inspired.    

I hope these current promises by law enforcement officials are not as hollow as earlier ones, because continuing our society's continuing failure to rein in corrupt business practices via law enforcement and regulation may lead a desperate populace to more radical approaches. The UK Labor Party just elected a Marxist leader (see this Reuters report.)  One wonders how long it will be before anger at the larger oligarchy, of which health care leadership is merely a part, boils over in other countries, and in more radical ways.

Instead, we continue to advocate for true health care reform with the immediate priority of changing how health care organizations are led, and ensuring leadership that upholds health care values, is willing to be accountable, and is open, honest, transparent and ethical.  We still may have time to reform.  But the reform will have to be big and true.  If not, moderate voices may be drowned out, and the results may be worse than anyone could imagine.

Appendix - Pfizer's Previous Settlements


For all our posts on Pfizer, look here.

In the beginning of the 21st century, according to the Philadelphia Inquirer, Pfizer made three major settlements,
- In 2002, Pfizer and subsidiaries Warner-Lambert and Parke-Davis agreed to pay $49 million to settle allegations that the company fraudulently avoided paying fully rebates owed to the state and federal governments under the national Medicaid Rebate program for the cholesterol-lowering drug Lipitor.
- In 2004, Pfizer agreed to pay $430 million to settle DOJ claims involving the off-label promotion of the epilepsy drug Neurontin by subsidiary Warner-Lambert. The promotions included flying doctors to lavish resorts and paying them hefty speakers' fees to tout the drug. The company said the activity took place years before it bought Warner-Lambert in 2000.
- In 2007, Pfizer agreed to pay $34.7 million in fines to settle Department of Justice allegations that it improperly promoted the human growth hormone product Genotropin. The drugmaker's Pharmacia & Upjohn Co. subsidiary pleaded guilty to offering a kickback to a pharmacy-benefits manager to sell more of the drug.

Thereafter,
- Pfizer paid a $2.3 billion settlement in 2009 of civil and criminal allegations and a Pfizer subsidiary entered a guilty plea to charges it violated federal law regarding its marketing of Bextra (see post here).
- Pfizer was involved in two other major cases from then to early 2010, including one in which a jury found the company guilty of violating the RICO (racketeer-influenced corrupt organization) statute (see post here).
- The company was listed as one of the pharmaceutical "big four" companies in terms of defrauding the government (see post here).
- Pfizer's Pharmacia subsidiary settled allegations that it inflated drugs costs paid by New York in early 2011 (see post here). 
- In March, 2011, a settlement was announced in a long-running class action case which involved allegations that another Pfizer subsidiary had exposed many people to asbestos (see this story in Bloomberg).
- In October, 2011, Pfizer settled allegations that it illegally marketed bladder control drug Detrol (see this post).
- In August, 2012, Pfizer settled allegations that its subsidiaries bribed foreign (that is, with respect to the US) government officials, including government-employed doctors (see this post).
- In December, 2012, Pfizer settled federal charges that its Wyeth subsidiary deceptively marketed the proton pump inhibitor drug Protonix, using systematic efforts to deceive approved by top management, and settled charges by multiple states' Attorneys' General that it deceptively marketed Zyvox and Lyrica (see this post).
- In January, 2013, Pfizer settled Texas charges that it had misreported information to and over-billed Medicaid (see this post).
- In July, 2013, Pfizer settled charges of illegal marketing of Rapamune (see this post.)
- In April, 2014, Pfizer settled allegations of anti-trust law violations for delaying generic versions of Neurontin( see this post).
- In June, 2014, Pfizer settled another lawsuit alleging illegal marketing of Neurontin (see this post).

Princess Health and The Latest Example of the Anechoic Effect - AllTrials US Initiative Launches to Deafening Media Silence. Princessiccia

Princess Health and The Latest Example of the Anechoic Effect - AllTrials US Initiative Launches to Deafening Media Silence. Princessiccia

AllTrials anechoic effect suppression of medical research

Gusty 13:12 Add Comment

Every now and then, someone tries to persuade me how much more open discussion of various kinds of recent unpleasantness in health care has become in the US. I admit there has been more media attention to certain issues, but unfortunately must maintain that the issues most likely to be make those who profit the most from our current health care system uncomfortable remains anechoic. Now I have my latest example

AllTrials

AllTrials is a UK based organization that advocates for registration and public reporting of all clinical trials.  AllTrials explains the reasons for this simply:

Clinical trials are the best way we have of testing whether a medicine is safe and effective. They can involve thousands of people, patients and healthy volunteers, and take years to complete.

Results from around half of all clinical trials remain hidden

Trials with negative results are twice as likely to remain unreported as those with positive results. This means that people who make decisions about medicines don�t have full information about the benefits and risks of treatments we use every day. Read our 8 page briefing note on missing trials here.

Thousands of clinical trials have never been publicly registered

There is no complete list of all clinical trials, so we don�t even know that some trials have taken place, never mind what was found in them.

The contributions of hundreds of thousands of patients are unused and unusable

Patients volunteer for clinical trials because they expect that what was found in the trial will be of use to doctors who make decisions about treatments and to researchers who are studying the condition. Trial participants have told us that the culture of secrecy around clinical trial reporting is a betrayal of their trust. Read their words here.

AllTrials has garnered considerable support in the UK.

On Health Care Renewal, we have been discussing the problem of suppressed clinical research for a long time, and have made similar arguments.  Up to now, I have chosen not to post a lot about AllTrials because as a UK based movement, it was getting considerable press coverage in the UK, and garnering considerable support there.  I did not think the movement needed what meager help a Health Care Renewal post would provide.

The Anechoic AllTrials USA Launch

But now, AllTrials has come to America.  And it perhaps should not be a surprise that its advent on this side of the pond generated essentially no notice, particularly, no notice in the US mainstream media or in US scholarly health care and medical journals.  

The announcement of the AllTrials US initiative appeared on the organization's website, and on the Biomed Central blog..  A press release appeared on the PRNewswire.  The American Academy of Family Practice (AAFP) announced its participation on its website.   The move received support from a post on the PLoS Public Health Perspectives blog, and perhaps surprisingly, from the UK based Financial Times.

Otherwise, at least according to my web searching efforts, there has been silence.  I found nothing in major media outlets, nothing in medical journals, and even nothing on the websites of the few US professional societies other than the AAFP that are listed as AllTrials USA supporters (that is, the American College of Obstetricians and Gynecologists, American College of Physicians and the American College of Chest Physicians). 

The Anechoic Effect Continues

We have frequently discussed the anechoic effect, the phenomenon that information or discussion that could challenge or discomfit the powers that be in the US health care often generates no echoes.  In effect, suppression of clinical research in itself is an example of the anechoic effect.

Why might even discussion that allows that clinical research might be suppressed invoke the cone of silence?

Looking at AllTrials literature may not be too helpful in providing an answer to this question.  The AllTrials organization is adept at discussing the reasons that clinical trials should not be suppressed, but has been very diplomatic about why they actually are suppressed.

On the other hand, its seems logical that when clinical trials are sponsored by organizations, such as pharmaceutical, biotechnology and device companies, to assess their own products, company management might get strong incentives to ensure that such research ends up making their products look good.  Sponsored research could be manipulated (in terms of the formal hypotheses it tests, its design, implmentation, and analysis) to increase the likelihood that the results would favor the sponsor.  When all else fails, the sponsor could suppress research that fails to make its products look good.  There is at least suggestive evidence that this occurs.  For example, see the now classic study by Turner et al that showed that clinical research sponsored by pharmaceutical companies to assess their own antidepressants were much more likely to be published if the results favored their own products.

So I suspect that the management of many health care organizations, particularly but not exclusively pharmaceutical, biotechnology, and device companies may not be very comfortable discussing the problem of suppressed research, or with measures designed to uncover such research.  Further, as we have discussed frequently, such companies have financial arrangements with individual health care professionals, health care academics, academic health care organizations, and a variety of other organizations such as medical societies and patient-advocacy groups.  These arrangements can constitute individual and institutional conflicts of interest.  It is not impossible that such financial relationships might influence such individuals and groups to want to avoid the topic of research suppression.

Yet it is striking that the important AllTrials USA initiative, an offshoot of an organization that has certainly got some attention in another English speaking country, has generated NO media or medical/ health care journal coverage in the US so far.

We cannot expect any real improvement in the dysfunctional US health care system while it still appears to be taboo to discuss many of its most dysfunctional aspects.  True health care reform requires open and honest discussion of these issues, that is, we need real free speech and a real free press in health care.  

ADDENDUM (21 August, 2015) - This post was republished on the Naked Capitalism blog. 

Princess Health and Two New Independent Reports on the Death of Dan Markingson, But Now What Will Happen? . Princessiccia

Princess Health and Two New Independent Reports on the Death of Dan Markingson, But Now What Will Happen? . Princessiccia

anechoic effect AstraZeneca atypical anti-psychotics clinical trials conflicts of interest manipulating clinical research research subjects suppression of medical research University of Minnesota

Gusty 13:53 Add Comment

Years after his death, there is now a little more clarity about the clinical trial in which Dan Markingson was enrolled when he died.  Whether this clarity will have any impact remains to be seen.

We most recently posted about the aftermath of Mr Markingson's death here, (and see posts in 2013 here, and in 2011 here.)  Very briefly, Mr Markingson was an acutely psychotic patient enrolled in a drug trial sponsored by Astra Zeneca at the University of Minnesota.  His enrollment was said to be voluntary although at the time he enrolled he had been under a stayed order that could have involuntarily committed him to care.  Despite his mother's ongoing and vocal concerns that he was not doing well on the study drug and under the care of trial investigators, he continued in the trial until he died violently by his own hand.  After his death, his mother Mary Weiss, friend Mike Howard, and University of Minnesota bioethics professor Carl Elliott campaigned for a fair review of what actually happened.  University managers not only rebuffed their concerns, but harshly criticized Professor Elliott, and ended up reprimanding him for "unprofessional conduct."

Two New Reports

In the last few weeks, two new independent reports on the case appeared.  Both vindicated the concerns and questions raised by Mary Weiss, Mike Howard, and Prof Elliott.

Association for Accreditation of Human Research Protection

One, called for by the University of Minnesota faculty senate, was by the Association for Accreditation of Human Research Protection,  and said that the university left research subjects "susceptible to risks that otherwise would be avoidable" (see this Minneapolis Star-Tribune article.)  Furthermore, according to a post in the Science Insider blog from the American Association for the Advancement of Science, it said,

[T]he external review team believes the University has not taken an appropriately aggressive and informed approach to protecting subjects and regaining lost trust,

Also, it said the university has been

assuming a defensive posture. In other words, in the context of nearly continuous negative attention, the University has not persuaded its critics (from within and outside the University) that it is interested in more than protecting its reputation and that it is instead open to feedback, able to acknowledge its errors, and will take responsibility for deficiencies and their consequences.

Finally, it noted a "climate of fear" in the Department of Psychiatry.

Office of the Legislative Auditor for the State of Minnesota

The second report, available in full here,was from the Office of the Legislative Auditor for Minnesota.  If anything, it was more damning. Its summary included,

the Markingson case raises serious ethical issues and numerous conflicts of interest, which University leaders have been consistently unwilling to acknowledge. They have repeatedly claimed that clinical research at the University meets the highest ethical standards and dismissed the need for further consideration of the Markingson case by making misleading statements about past reviews. This insular and inaccurate response has seriously harmed the University of Minnesota�s credibility and reputation.

It seemed to affirm in detail nearly all of Weiss', Howard's and Elliott's concerns.  It recommended that the University should suspend new psychiatric drug trials until the problems it identified were remedied (see Star-Tribune article here.)

Vindication, but Will It Lead to Progress?  

Taken together, these reports vindicate the work of Mr Markingson's mother, friend, and academic watchdog Professor Elliott and their supporters.  As the Star-Tribune reported,

'Over the past eleven years the University of Minnesota has made us feel as if we have no voice, no rights and absolutely nothing remotely called justice,' wrote Mike Howard, a close friend to Markingson�s mother, in a letter in the audit. 'This report is the first step toward accountability.'

The Minnesota Post added the response of Professor Elliott and a colleague,

'It�s nice to have an independent confirmation of what we�ve been telling the university for five years, but which they have refused to listen to,' he told MinnPost on Thursday.

Elliott said he is not convinced, however, that Kaler and other university leaders are going to take responsibility for what happened in the Markingson case � or take the necessary steps to fix the problem going forward.

'One of the most worrying findings in the report was the widespread belief on campus that the university leadership doesn�t care about human study subjects,' he said.

Leigh Turner, another U bioethicist who has also been outspoken about the issues raised by the Markingson case, expressed similar concerns. 'Can we expect reform from the very people who have done nothing for the past several years?' he said in a phone interview.

'I hope there�s some change,' he added. 'But the fact that [Markingson died in 2004] and it�s now 2015, I think hope has to be tempered with a dose of realism. There are some very powerful forces interested in minimizing the findings and suggesting that there are only minor things that need to be done.'

It appears there a several major remaining questions.

What Were the Underlying Causes?

Although both reports went into some detail about what happened to Mr Markingson, they seemed not to dwell on why it happened.  They did not seem to address relevant contextual factors, policies, and decisions.  For example, the report by the Office of the Legislative Auditor included,

We understand that the University of Minnesota has been and should continue to be an institution that delivers not only high quality medical care but also engages in cutting edge medical research� research that does pose risks to human subjects. In addition, we do not question the appropriateness of the University obtaining money from pharmaceutical and other medical companies to support that research. However, in every medical research study�whether supported with public or private money�the University must always make the protection of human subjects its paramount responsibility.

However, as we and many others more erudite have discussed frequently, clinical research that evaluates products or services made by the commercial sponsors of the research has proven to be highly susceptible to manipulation by these sponsors to increase the likelihood that the results will serve marketing purposes, and suppression if the manipulation fails to produce the wanted results.  Commercial sponsors often strongly influence the design, implementation, analysis and dissemination of clinical research.  Often their influence is mediated by financial relationships with individual researchers and with academic institutions who seem more and more beholden to outside sponsors, that is, by conflicts of interest.  The report by the Auditor noted pressures, including financial pressures on the physician who ran the study in which Mr Markingson was a subject to enroll more patients and keep them enrolled.  To protect patients better in the future, in my humble opinion the relationships among commercial sponsors, academic medical institutions, and individual researchers need further consideration.  Is the easy money supporting research coming from commercial firms with vested interests in the outcome of that research really worth the risks of biased results, hidden results, and to research subjects?   

Will Anything Change and Will Anyone be Held Accountable?

Once these two reports were delivered, it now seems to be up to university managers to make needed changes.  In general, these are the same managers who are described above as so "defensive," who not only ignored complaints, but appeared to try to silence those who complained.  If they are left in charge, why should we expect them to make any meaningful changes?  Instead, should they  not be held accountable for their actions?  

Will the University Cease Hostilities Against Dr Elliott?

Again, as noted above, university managers did not merely disagree with Professor Elliott.  They disparaged him, appeared to try to intimidate him, and reprimanded him.  It seems at the very least he is owed an apology.  So far, nothing in the news coverage suggests he has or will receive one.

Will Anyone Notice? 

So far, this case has gotten good coverage in Minnesota media.  However, it has largely been ignored in the national media.  Beyond Minnesota, I could only find mention in some blogs, e.g., in PharmaLot by Ed Silverman, and in Forbes by Judy Stone.  I have seen nothing in any US medical or health care journal, although the British Medical Journal did cover it in a news feature.  This case clearly has global implications, and ought to be considered one of the most important cases illustrating the perils of commercially sponsored human research, but it remains proportionately anechoic.

Summary

The latest reports seem only to confirm that clinical research at major academic institutions has gone way off track.  It now seems that in their haste to bring in external funding, university administrators and the academic researchers who are beholden to them have sadly neglected the protection of their own patients.  As we have said ad infinitum, true health care reform would turn leadership of health care organizations over the people who understand and are willing to uphold the mission of health care, and particularly willing to put patients' and the public's health, and the integrity of medical education and research when applicable, ahead of the leaders' personal interests and financial gain.

ADDENDUM (25 March, 2015) - See also numerous posts by Professor Elliott on the Fear and Loathing in Bioethics blog,  by Bill Gleason in the Periodic Table blog,  and by Mickey Nardo on the 1BoringOldMan blog. 

ADDENDUM (30 March, 2015) - Note that after receiving offline comments, I changed the first paragraph to emphasize the clarity is about the trial, rather than the patient's death, and second paragraph to clarify that the order to commit was stayed.

Princess Health and The Reappearance of a Ghost of Seasons Past. Princessiccia

Princess Health and The Reappearance of a Ghost of Seasons Past. Princessiccia

Actonel conflicts of interest ghost writing manipulating clinical research Procter and Gamble suppression of medical research University of Sheffield whistle-blowers

Gusty 08:01 Add Comment

About a year after we started Health Care Renewal, in late 2005, we wrote multiple posts about the complex and unfortunate case of Dr Aubrey Blumsohn's attempts to keep a research project honest. The early posts were here, here, here, and here. In this post, we summarized the case thus:

• Dr Aubrey Blumsohn, a senior lecturer at Sheffield University, and Professor Richard Eastell performed a research project on the effects of the drug risedronate (Actonel, made by Procter & Gamble Pharmaceuticals [P&G]) under a contract between P&G and the University.
• Although the research contract designated Blumsohn and Eastell as "Investigators" under whose direction the project would be carried out, Blumsohn was not given access to the original data collected by the project.
• Despite numerous requests, (like this one), P&G refused access to this data repeatedly.
  Blumsohn was concerned that he and Eastell could be accused of scientific fraud if they continued to make presentations and write articles and abstracts without access to the data which they were supposedly writing about.
• Blumsohn became suspicious that some of the analyses done by P&G could be misleading, especially related to a graph shown to him that omitted 40% of patient data.
• Blumsohn objected to P&G arranging for papers and abstracts to be written by a professional writer, but with Blumsohn listed as first author. Blumsohn was concerned that such ghost-written documents were mainly meant to convey "key messages" in support of P&G's commercial interests.
• Eastell warned Blumsohn not to aggravate P&G, because the company was providing a grant to the University which "is a good source of income."
• After repeated failed attempt to get the data, Blumsohn complained to numerous officials at Sheffield University, including Eastell, medical school Dean Tony Weetman, University Vice-Chancellor Robert Boucher, and the Head of the University's Department of Human Resources, Ms R Valerio.
• Still unable to get the data, he spoke with news reporters about his case. At this point, Sheffield suspended him, but then offered him a severance agreement if he signed a contract binding him not to make any detrimental or derogatory statements about the University and its leaders.

So the case involved suppression and manipulation of research, ghost-writing, institutional conflicts of interest, and attempts to silence a whistle blower. It provides lessons about the downsides of letting commercial firms sponsor and hence control human research designed to evaluate the products or services they sell; and of academic medicine becoming dependent on research money from such firms for such research. Although Health Care Renewal, being US based, most often writes about such issues in the US, this case is a reminder that they are global. (Note that we posted more about this case in 2006, here, here and here, but since then it has not gotten much public attention.)

Last weekend the (UK) Guardian returned to it:

The Guardian has learned that one of Britain's leading bone specialists is facing disciplinary action over accusations that he was involved in 'ghost writing'.

The General Medical Council will call Professor Richard Eastell in front of a fitness to practice committee. Eastell, a bone expert at Sheffield University, has admitted he allowed his name to go forward as first author of a study on an osteoporosis drug even though he did not have access to all the data on which the study's conclusions were based. An employee of Proctor and Gamble, the US company making Actonel, was the only author who had all the figures.

Experts believe the practice is widespread in Britain.

In a letter published in the Journal of Bone and Mineral Research, which carried the original study, he stated: 'In the original paper one of the authors, a statistician working for P&G, Ian Barton, had full access to all the data.' The authors had full access to all the analyses of the data that they requested, he said � but those analyses were carried out by the company.

The letter, published in 2007, also acknowledged flaws in the study. A later independent analysis of the data 'identified some errors and poor practice', he wrote. The study was designed to show the strengths of Actonel which was in fierce competition with a rival bone-strengthening drug called Fosamax, made by Merck.

Eastell's paper concerned a study carried out on behalf of Proctor and Gamble, comparing the bone density of women prescribed Actonel with others who were not. Only the company knew which women were on the drug and which were taking something else.

Eastell's colleague, Dr Aubrey Blumsohn, wanted the codes which would say which of the patients who suffered fractures had been on the drug. The company refused. Blumsohn took his concerns to Eastell, but in a conversation which Blumsohn says he taped , Eastell said he was concerned that persistent requests might damage the relationship they had with the company. Eastell is said to have told him: 'The only thing that we have to watch all the time is our relationship with P&G. Because � we have the big Sheffield Centre Grant [from P&G] which is a good source of income, we have got to really watch it.' .

So, after four years, this case has generated an official hearing of sorts. The hearing is obviously late, and seemingly will only be devoted to only one aspect of this case (ghost writing). However, at least our friends in the UK are doing something. I cannot recall a single case that resulted in any serious consideration of imposing negative consequences on anyone who was accused of suppressing research, manipulating research, endorsing ghost-writing, or intimidating a whistle-blower. In fact, many of the more troubling cases have never resulted in any sort of public discussion either at the institutions at which they occurred, or at any organization with relevant regulatory, or even just moral authority. So the GMC hearing is at least a step forward. Two cheers for the British GMC, and none for US universities, academic medical centers, professional societies, and government regulators.

(If anyone can remind me of a case in which there was a public discussion at the relevant institution, or some public consideration of the case by a regulatory agency, professional society, or some group with moral authority, please remind me of it, and I would be happy to post about it.)

Princess Health and British Government Concludes GSK Suppressed Paxil (Seroxat) Data. Princessiccia

Princess Health and British Government Concludes GSK Suppressed Paxil (Seroxat) Data. Princessiccia

clinical trials GlaxoSmithKline Paxil pharmaceuticals SSRIs suppression of medical research

Gusty 13:30 Add Comment

Last year, we summarized the results of a BBC investigation broadcast on the television program Panorama that charged that GlaxoSmithKline "distorted trial results of an anti-depressant, [Seroxat in the UK, Paxil in the US, chemical name paroxetine] covering up a link with suicidal teenagers." (See also the links in that post to extensive discussion on the Clinical Psychology and Psychiatry Blog.)

The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has just completed an investigation, and it is fitting to quote the BBC story about its results.

It comes after the drugs regulator announced GlaxoSmithKline would not face criminal proceedings over claims it withheld information on Seroxat.

But they warned GSK should have been quicker to raise the alarm on the risk of suicidal behaviour associated with the antidepressant in the under-18s.

GSK has rejected claims it improperly withheld drug-trial information.

The Medicines and Healthcare products Regulatory Agency (MHRA) received data from clinical trials in May 2003 showing that patients under 18 had a higher risk of suicidal behaviour if they were treated with Seroxat than if they received a placebo.

Data also showed that Seroxat was not effective for treating depression in children and adolescents.

But Professor Kent Woods, MHRA chief executive said they were disappointed GSK had not given them information earlier and that drugs firms had an "ethical responsibility".

"I remain concerned that GSK could and should have reported this information earlier than they did.

"All companies have a responsibility to patients, and should report any adverse data signals to us as soon as they discover them.

The government decided not to pursue criminal charges, mainly because of "important weaknesses in drug safety legislation in force at the time."

Also,

Health minister Dawn Primarolo said the government would take immediate steps to secure a strengthening of the law in the UK and Europe.

She also said they wanted to make it clear to all pharmaceutical companies that, "notwithstanding the limitations that may exist in the law, they should disclose any information they have that would have a bearing on the protection of health".

The Guardian reported the forceful opinions of the [UK] Mental Health Foundation chief executive, Andrew McCulloch,

It is totally unacceptable to hear that, when information can be made available at speed, young people may have taken their own lives due to a lack of transparency by a pharmaceutical company.

Woods further commented in another article in the Guardian,

I really feel there is an ethical obligation that pharmaceutical companies ought to recognise and it seems to have been lost. Twenty years ago I was a prescribing doctor and I took it for granted that if there was information relevant to the drug I was going to prescribe, then it would be available. We're talking about something which has direct relevance to health and safety.

The Guardian also noted that Woods "could not rule out the possibility that other companies were sitting on unpublished data that could cause them commercial damage."

So, in case there was any doubt, based on this UK government report, it seems very clear that GSK suppressed data about the adverse effects of Seroxat in an effort not preserve sales. This was a blatant effort to put company profits ahead of patient well-being and a slap at the integrity of the clinical science data base. This has hardly been the only case of suppression of clinical research data because it reflected poorly on some company's products or services.

And pharmaceutical executives wonder why no one trusts them anymore?

I doubt there is any way to secure the integrity clinical research short of banning all involvement by corporations with vested interests in having specific research studies come out in ways that favor their products or services.

See also the forceful comments by Dr Aubrey Blumsohn on the Scientific Misconduct Blog. He called it "a day of shame."

Princess Health and An Australian Survey of Threats to Research Integrity. Princessiccia

Princess Health and An Australian Survey of Threats to Research Integrity. Princessiccia

manipulating clinical research suppression of medical research surveys

Gusty 07:48 Add Comment

Another important article on threats to the integrity of clinical research has appeared in the Medical Journal of Australia. (Henry DA et al. Medical specialists and pharmaceutical industry-sponsored research: a survey of the Australian experience. Med J Aust 2005; 182: 557-560.)
The authors sent a survey to 5000 Australian specialists, excluding general practitioners, but also surgeons and anesthesologists, and obtained a 39% response rate. 388 specialists (41% of respondents) had done pharmaceutical industry sponsored research. Of these,

• 100 (25.7% of those engaging in research) reported that the first draft of a research report was written by pharmaceutical company or contract research organization personnel
• 55 (14.2%) reported a delay in presentation or publication of key study findings
• 41 (10.6%) reported failure to publish key findings
• 22 (5.7%) reported editing of the report to make the drug appear better than was justified by the study results
• 18 (4.6%) reported concealment of relevant findings.

This study suggests that manipulation and suppression of research results in favor of commercial research sponsors' products is an international pheonomenon, and one that involves not only academic researchers but those in private practice.
An accompanying editorial (Gotzsche PC. Research integrity and pharmaceutical industry sponsorship. Med J Aust 2005; 182: 549-550) suggested that "testing drugs in patients" should be "a public enterprise." It asked, "who would buy a washing machine that is five or 10 times more expensive than other washing machines just because its manufacturer has compared it with other machines and claims that it is the best?"
Thanks to Sue Pelletier's Capsules blog for the tip.

Princess Health and An Australian Survey of Threats to Research Integrity.Princessiccia

Princess Health and An Australian Survey of Threats to Research Integrity.Princessiccia

manipulating clinical research suppression of medical research surveys

Gusty 07:48 Add Comment

Another important article on threats to the integrity of clinical research has appeared in the Medical Journal of Australia. (Henry DA et al. Medical specialists and pharmaceutical industry-sponsored research: a survey of the Australian experience. Med J Aust 2005; 182: 557-560.)
The authors sent a survey to 5000 Australian specialists, excluding general practitioners, but also surgeons and anesthesologists, and obtained a 39% response rate. 388 specialists (41% of respondents) had done pharmaceutical industry sponsored research. Of these,

• 100 (25.7% of those engaging in research) reported that the first draft of a research report was written by pharmaceutical company or contract research organization personnel
• 55 (14.2%) reported a delay in presentation or publication of key study findings
• 41 (10.6%) reported failure to publish key findings
• 22 (5.7%) reported editing of the report to make the drug appear better than was justified by the study results
• 18 (4.6%) reported concealment of relevant findings.

This study suggests that manipulation and suppression of research results in favor of commercial research sponsors' products is an international pheonomenon, and one that involves not only academic researchers but those in private practice.
An accompanying editorial (Gotzsche PC. Research integrity and pharmaceutical industry sponsorship. Med J Aust 2005; 182: 549-550) suggested that "testing drugs in patients" should be "a public enterprise." It asked, "who would buy a washing machine that is five or 10 times more expensive than other washing machines just because its manufacturer has compared it with other machines and claims that it is the best?"
Thanks to Sue Pelletier's Capsules blog for the tip.

Princess Health and New Book on "Olivieri Affair". Princessiccia

Princess Health and New Book on "Olivieri Affair". Princessiccia

Nancy Olivieri suppression of medical research

Gusty 07:11 Add Comment

The NY Times reviewed a new book on what may be called the "Olivieri affair," one of the most notorious cases of research suppression from the late 1990's. The case, which involved allegations that the Canadian drug manufacturer Apotex attempted to suppress results of Olivieri's research which showed that the drug , defirapone, or L1, had unexpected adverse effects, was investigated by the Canadian Association of University Teachers, who issued an extensive report. The book, The Drug Trial, by Miriam Shuchman, apparently takes a revisionist approach, and is much more critical of Olivieri's role in the case than previously published reports. (See also this article on the book from MacLeans.) I haven't read the book so can't comment on its contents.

Princess Health and New Book on "Olivieri Affair".Princessiccia

Princess Health and New Book on "Olivieri Affair".Princessiccia

Nancy Olivieri suppression of medical research

Gusty 07:11 Add Comment

The NY Times reviewed a new book on what may be called the "Olivieri affair," one of the most notorious cases of research suppression from the late 1990's. The case, which involved allegations that the Canadian drug manufacturer Apotex attempted to suppress results of Olivieri's research which showed that the drug , defirapone, or L1, had unexpected adverse effects, was investigated by the Canadian Association of University Teachers, who issued an extensive report. The book, The Drug Trial, by Miriam Shuchman, apparently takes a revisionist approach, and is much more critical of Olivieri's role in the case than previously published reports. (See also this article on the book from MacLeans.) I haven't read the book so can't comment on its contents.

Princess Health and Opinions About the Regulating the Pharmaceutical Industry. Princessiccia

Princess Health and Opinions About the Regulating the Pharmaceutical Industry. Princessiccia

marketing pharmaceuticals suppression of medical research

Gusty 07:12 Add Comment

Two major newspapers have published opinion pieces condemning current pharmaceutical industry practices, and calling for better regulation of the industry.
The Atlanta Journal-Constitution noted how pharmaceutical companies promised to supply clinical trial data to a government sponsored web-site, but often provided data too limited to be meaningful. The editorial suggested "given the results so far, the next step would be to convert the voluntary government Web site to a national registry and threaten stiff financial penalties for companies that fail to comply."
The paper also published a response by Peter S Kim, President of Merck Research Laboratories, who said "given its track record of publishing data, the implication that Merck has hidden data is both unfair and inaccurate." He didn't address specific charges that Merck has hidden or manipulated data (for links to posts on these charges, see this.)
Meanwhile, an op-ed in the Denver Post stated "drug-making has become a very competitive industry, which may be putting profits before our health." Furthermore, it suggested that the US Food and Drug Administration is "too outdated, inadequate, and riddled with conflicts of interest to regulate the business of medical drugs." Instead, it proposed a new regulatory structure to ensure "that medical drugs would have to be safe for their intended use, that full information about potential harmful effects would be given to consumers and the medical community, and that harmed consumers would have the right to redress under exisiting product liability laws."
Clearly, there seems to be increasing sentiment for a renewal of the regulatory structure for the pharmaceutical industry. It may also be reasonable to suggest that other health care sectors, especially hospitals/ academic medical centers, and managed care organizations/ insurers, may be called upon to quickly clean up their acts, or also be subject to new and more rigorous regulation.

Princess Health and Opinions About the Regulating the Pharmaceutical Industry.Princessiccia

Princess Health and Opinions About the Regulating the Pharmaceutical Industry.Princessiccia

marketing pharmaceuticals suppression of medical research

Gusty 07:12 Add Comment

Two major newspapers have published opinion pieces condemning current pharmaceutical industry practices, and calling for better regulation of the industry.
The Atlanta Journal-Constitution noted how pharmaceutical companies promised to supply clinical trial data to a government sponsored web-site, but often provided data too limited to be meaningful. The editorial suggested "given the results so far, the next step would be to convert the voluntary government Web site to a national registry and threaten stiff financial penalties for companies that fail to comply."
The paper also published a response by Peter S Kim, President of Merck Research Laboratories, who said "given its track record of publishing data, the implication that Merck has hidden data is both unfair and inaccurate." He didn't address specific charges that Merck has hidden or manipulated data (for links to posts on these charges, see this.)
Meanwhile, an op-ed in the Denver Post stated "drug-making has become a very competitive industry, which may be putting profits before our health." Furthermore, it suggested that the US Food and Drug Administration is "too outdated, inadequate, and riddled with conflicts of interest to regulate the business of medical drugs." Instead, it proposed a new regulatory structure to ensure "that medical drugs would have to be safe for their intended use, that full information about potential harmful effects would be given to consumers and the medical community, and that harmed consumers would have the right to redress under exisiting product liability laws."
Clearly, there seems to be increasing sentiment for a renewal of the regulatory structure for the pharmaceutical industry. It may also be reasonable to suggest that other health care sectors, especially hospitals/ academic medical centers, and managed care organizations/ insurers, may be called upon to quickly clean up their acts, or also be subject to new and more rigorous regulation.

Princess Health and A Troubling Study of the Contracts Between Medical Schools and Corporate Research Sponsors. Princessiccia

Princess Health and A Troubling Study of the Contracts Between Medical Schools and Corporate Research Sponsors. Princessiccia

conflicts of interest institutional conflicts of interest manipulating clinical research suppression of medical research

Gusty 12:45 Add Comment

The NEJM article about contracts for clinical trials between academic health centers (AHCs) and pharmaceutical companies mentioned in an earlier post deserves further attention. (The study is available here, and its citation is Mello MM, Clarridge BR, Studdert DM. Academic medical centers' standards for clinical-trial agreements with industry. N Engl J Med 2005; 352: 21.)

First, let me summarze the study's design. The authors sent a survey to senior administrators in the offices of sponsored research in 122 medical schools. They received responses from 107, for 91% response rate, excluding four schools that did no clinical research. They asked the administrators questions about provisions they would usually allow in contracts between their medical schools and corporate sponsors. The proportions who would allow some particular research practices follow:

• The sponsor will own the data produced by the research - 80%
• The sponsor will store the data and release portions to the investigator - 35%
• The investigators (whether at your site or any other site) are not permitted to alter the study design after the agreement is executed - 68%
• The sponsor is permitted to alter the study design after the agreement is executed - 62%
• The sponsor may prohibit individual site investigators from publishing manuscripts independently of the sponsor or group - 15%
• The sponsor may include its own statistical analysis in manuscripts - 24%
• The sponsor will write up the results for publication and the investigators may review the manuscript and suggest revisions - 50%
• While the trial is going on, the investigators may not discuss research results (including presentations at scientific meetings) with people not involved in the trial - 66%
• After the trial is over, the investigators may not discuss research results (including presentations at scientific meetings) until the sponsor consents to dissemination - 21%
• The terms of the clinical-trial agreement are confidential - 62%
• After the trial is over, the industry sponsor may prohibit investigators from sharing raw research data with third parties - 41%

In summary, this study suggests that some medical schools will acquiesce to contracts that prevent their faculty from having meaningful control over research projects for which they are the ostensible investigators. Some medical schools will allow corporate research sponsors to manipulate the design, analysis, and interpretation of results to increase the likelihood of getting the results the sponsor wants. For example, 50% of medical schools would allow the corporate sponsor to write manuscripts reporting on study results, and only allow faculty to "suggest revisions." Thus, many medical schools acquiesce to contracts that could allow corporate sponsors to ghost-write articles. Furthermore, more than half of the medical schools acquiesce to contracts that are kept confidential, preventing easy discovery of manipulation of the conduct and dissemination of the research by the corporate sponsor.
(To see specific techniques that corporate sponsors may use to increase the likelihood that research produces the results they want, see our earlier post about the article entitled "Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies" by Richard Smith.)
To underline the context, in my experience, to do clinical research, most medical school faculty are strongly pressured by their institutions to obtain external funding to support this work. Those who cannot obtain funding within a few years of unemployment often have to find something else to do other than research. However, although faculty are expected to find sources of funding, it is generally the medical schools or academic medical centers, not the researchers, who negotiate research agreements, and although such agreements may bind faculty members, the money paid under their auspices generally goes directly to the faculty member's employer. Thus, individual researchers are under considerable pressure to find grant and contract funding, and to keep their financial sponsors happy, but must work under whatever contract provisions their employers negotiate.
The New England Journal of Medicine article clearly suggests that some medical schools allow researchers to be bound by agreements that allow the study's sponsor to manipulate study design, analysis, and interpretation to make it more likely that the results will be to the sponsor's liking. Since clinical trials enroll real human beings as subjects with the promise that the data they contribute, and the risks they run, will lead to valid scientific results, allowing such manipulation appears to not only likely to produce biased results, but also to be allow unethical exploitation of human subjects, and thus is in conflict with the medical school's scientific and humanitarian mission.
This is yet another illustration of leaders of powerful health care organizations acting in conflict with physicians' and medical researchers' core values.
One can only hope that publicizing such practices will lead to more ethical research, and less exploitation of human subjects.
By the way, I do not in any sense mean to blame the research administrators who must try to negotiate these contracts. Note that 69% of the administrators "perceived that competition for research funds created pressure on administrators to compromise on the language of the contract." 24% described the pressure as "great." I do blame the higher leadership of the medical schools for fostering a climate in which money is more important than doing valid, ethical research. This raises several important questions:

• Why don't some medical school leaders enforce clearer ethical standards for clinical research sponsored by industry?
• Are they so worried about getting the money, and so worried that they will lose contracts if they insist on ethical standards?
• Are they so steeped in the exteme relativism of the post-modernist university that they don't believe in such standards?
• Are they so used to violating their own mission to support political causes, as is documented again and again on the FIRE web-site, that they aren't troubled by violating their mission for economic reasons?

Maybe it's time we start trying to address such questions.

Princess Health and A Troubling Study of the Contracts Between Medical Schools and Corporate Research Sponsors.Princessiccia

Princess Health and A Troubling Study of the Contracts Between Medical Schools and Corporate Research Sponsors.Princessiccia

conflicts of interest institutional conflicts of interest manipulating clinical research suppression of medical research

Gusty 12:45 Add Comment

The NEJM article about contracts for clinical trials between academic health centers (AHCs) and pharmaceutical companies mentioned in an earlier post deserves further attention. (The study is available here, and its citation is Mello MM, Clarridge BR, Studdert DM. Academic medical centers' standards for clinical-trial agreements with industry. N Engl J Med 2005; 352: 21.)

First, let me summarze the study's design. The authors sent a survey to senior administrators in the offices of sponsored research in 122 medical schools. They received responses from 107, for 91% response rate, excluding four schools that did no clinical research. They asked the administrators questions about provisions they would usually allow in contracts between their medical schools and corporate sponsors. The proportions who would allow some particular research practices follow:

• The sponsor will own the data produced by the research - 80%
• The sponsor will store the data and release portions to the investigator - 35%
• The investigators (whether at your site or any other site) are not permitted to alter the study design after the agreement is executed - 68%
• The sponsor is permitted to alter the study design after the agreement is executed - 62%
• The sponsor may prohibit individual site investigators from publishing manuscripts independently of the sponsor or group - 15%
• The sponsor may include its own statistical analysis in manuscripts - 24%
• The sponsor will write up the results for publication and the investigators may review the manuscript and suggest revisions - 50%
• While the trial is going on, the investigators may not discuss research results (including presentations at scientific meetings) with people not involved in the trial - 66%
• After the trial is over, the investigators may not discuss research results (including presentations at scientific meetings) until the sponsor consents to dissemination - 21%
• The terms of the clinical-trial agreement are confidential - 62%
• After the trial is over, the industry sponsor may prohibit investigators from sharing raw research data with third parties - 41%

In summary, this study suggests that some medical schools will acquiesce to contracts that prevent their faculty from having meaningful control over research projects for which they are the ostensible investigators. Some medical schools will allow corporate research sponsors to manipulate the design, analysis, and interpretation of results to increase the likelihood of getting the results the sponsor wants. For example, 50% of medical schools would allow the corporate sponsor to write manuscripts reporting on study results, and only allow faculty to "suggest revisions." Thus, many medical schools acquiesce to contracts that could allow corporate sponsors to ghost-write articles. Furthermore, more than half of the medical schools acquiesce to contracts that are kept confidential, preventing easy discovery of manipulation of the conduct and dissemination of the research by the corporate sponsor.
(To see specific techniques that corporate sponsors may use to increase the likelihood that research produces the results they want, see our earlier post about the article entitled "Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies" by Richard Smith.)
To underline the context, in my experience, to do clinical research, most medical school faculty are strongly pressured by their institutions to obtain external funding to support this work. Those who cannot obtain funding within a few years of unemployment often have to find something else to do other than research. However, although faculty are expected to find sources of funding, it is generally the medical schools or academic medical centers, not the researchers, who negotiate research agreements, and although such agreements may bind faculty members, the money paid under their auspices generally goes directly to the faculty member's employer. Thus, individual researchers are under considerable pressure to find grant and contract funding, and to keep their financial sponsors happy, but must work under whatever contract provisions their employers negotiate.
The New England Journal of Medicine article clearly suggests that some medical schools allow researchers to be bound by agreements that allow the study's sponsor to manipulate study design, analysis, and interpretation to make it more likely that the results will be to the sponsor's liking. Since clinical trials enroll real human beings as subjects with the promise that the data they contribute, and the risks they run, will lead to valid scientific results, allowing such manipulation appears to not only likely to produce biased results, but also to be allow unethical exploitation of human subjects, and thus is in conflict with the medical school's scientific and humanitarian mission.
This is yet another illustration of leaders of powerful health care organizations acting in conflict with physicians' and medical researchers' core values.
One can only hope that publicizing such practices will lead to more ethical research, and less exploitation of human subjects.
By the way, I do not in any sense mean to blame the research administrators who must try to negotiate these contracts. Note that 69% of the administrators "perceived that competition for research funds created pressure on administrators to compromise on the language of the contract." 24% described the pressure as "great." I do blame the higher leadership of the medical schools for fostering a climate in which money is more important than doing valid, ethical research. This raises several important questions:

• Why don't some medical school leaders enforce clearer ethical standards for clinical research sponsored by industry?
• Are they so worried about getting the money, and so worried that they will lose contracts if they insist on ethical standards?
• Are they so steeped in the exteme relativism of the post-modernist university that they don't believe in such standards?
• Are they so used to violating their own mission to support political causes, as is documented again and again on the FIRE web-site, that they aren't troubled by violating their mission for economic reasons?

Maybe it's time we start trying to address such questions.