Lawyers to have cholesterol feast: lawsuits target Vytorin's makers - and, who is responsible for the "confusion?"

In today's news we find that Merck and Schering Plough are coming under lawsuits as a result of the ezetimibe/Vytorin controversy. This was perhaps to be expected:

Lawsuits target Vytorin's makers
Plaintiffs contend the firms knew the drug didn't work.
Sat, Jan. 26, 2008

By Karl Stark
Inquirer Staff Writer

First came the negative publicity, then the lawsuits.

Merck & Co. and Schering Plough Corp., makers of the cholesterol-lowering combination drug Vytorin, are getting hit with a wave of lawsuits asserting the companies knew its product didn't work and delayed telling the public about it.

At least 10 lawsuits have been filed in federal courts, with half the filings in New Jersey, where both parent companies are based. Other federal suits have landed in California, New York, Ohio and Colorado.

The drugmakers "reaped billions of dollars in profits" by failing to release negative results, asserted a class-action complaint filed by a Philadelphia firm on behalf of Lionel D. Galperin of Washington state. The companies also caused patients to spend more money on Vytorin, which sells for more than $100 for 30 pills, compared with a lower-cost generic, the suit alleges.

Here is where I step off the alleged "anti-pharma" bandwagon ... sort of.

While I have criticized Merck's and Schering's mammoth marketing campaign for these drugs here ("Merck and Vytorin ... Who, Exactly, is Confused?") and here ("Full page ads in major newspapers: Does pharma really spend twice on marketing what it spends on R&D?"), I believe lawsuits with the slant of "Bush lied, people died" (i.e., the firms knew the drug didn't work but withheld the information) are both unmerited and especially unhelpful to those attempting to advance medical science.

This claim is in part based on the following:

The companies completed the [Enhance] study [on these drugs] in April 2006 but did not release preliminary results until a press release was issued on Jan 14 [2008]. That was more than a month after congressional investigators had written to company executives, asking about the delay and demanding documents.

The implication is that actual knowledge of the results were withheld from the public to protect the drug. I do not believe this to be the case. I recall genuine excitement at Merck about Zetia's cholesteral-lowering effects, and great confidence that it was a true breakthrough drug that would generate much needed revenue after multiple drug failures and patent expirations. Clinical medicine, however, is full of surprises.

While such excitement could motivate a company to withhold negative new information, I have a different interpretation of why such delays occurred. Pharma is in a state of downsizing. At Merck, a company that carried on a succcesful business for over 100 years without downsizing, the mass downsizing that began in Nov. 2003 and continues to this day was a major cultural "hammer over the head."

Such social changes tend to sink morale very severely. While Catbert the Evil HR Director might find this amusing, most productive poeple do not. It's also something that cannot be "massaged away" with HR propaganda and "employee appreciation days." As I noted in "Happy Accidents in pharma doubtful: Tax Break Used by Drug Makers Failed to Add Jobs" here, the stress of losing a job is like the stress of a death in the family or a divorce, and the stress of fear of losing a job is also pretty darn bad. As the Alaska state government piece on "surviving a layoff" cited in the above posting states, "remaining employees become overworked, burned out, extremely unhappy and put in a position of fear and uncertainty." It doesn't exactly take a rocket scientist to realize this.

Anecdotally, I reside in a Merck community and hear as much about morale from my local car dealer, haircutter, family medicine physician, restaurant waiters, and others. In fact, I don't believe clinical trials information was withheld deliberately. I believe morale is low, departments are understaffed, and people are playing "CYA" like their lives depended on it (as their careers and ability to pay mortgages and support families depends on their jobs, this is actually not unwise).

Taking morale issues into account, and adding in the three late-stage pre-launch drug failures of 2003, resulting cultural shift to mass layoffs, and the Vioxx debacle, extra long "CYA" to make sure the data and conclusions are correct is understandible in context.

In such an environment, where overworked, stressed out people basically give themselves (effectively speaking) hourly pay raises via doing less per hour, and return to seeing jobs as a value-for-value proposition where an employee in a mirrorlike fashion gives a company what it has earned (i.e., deserves) in terms of their committment and willingness to make sacrifices, long delays in handling complex clinical trials results sets - this study, of course, being just one of many - is not at all surprising.

In addition, politics being what they are in any corporate layoff, many good people (the movers and shakers) get laid off, and other good people can't stand the environment and leave for greener pastures. This leaves behind many less capable colleagues to pick up the slack. I believe the cause of the delays in data release are more likely to be found attributable to low morale, a lesser % of "stars" among the workforce than necessary for optimal effectiveness, dysfunctional self protection-style politics, and resultant lowered productivity.

As an aside, it would not surprise me if recent chemical spills of "liquid mustard gas" into the creeks in my community had at its roots a similar cause:

Pharmaceutical giant Merck has agreed to pay $20 million in assorted fines, environmental improvements and cleanup costs to make up for killing untold fish, fouling drinking water supplies and spoiling a season of recreation on the Wissahickon Creek in Pennsylvania with a toxic "liquid mustard gas," the Philadelphia Inquirer is reporting. The massive impact came from an old-school problem: Dumping toxic chemicals down the drain at a vaccine plant, from which they reacted with chlorine disinfectants and washed into the creek, wreaking havoc downstream for miles.

I do not believe the company would deliberately withhold clinical trials data, and therefore do not believe a "deliberately withheld" charge is reasonable with regard to the ENHANCE clinical trial results on ezetimibe (Zetia) and ezetimibe-Zocor(Vytorin) . If there is a good basis for a lawsuit, perhaps the people who should be sued are those in management and in consulting organizations that recommended layoff strategies and stole the soul of such a once-stellar company.

The newspaper also notes the following:

...The drugmakers aren't the only ones facing scrutiny. Both the American College of Cardiology, which represents most cardiologists, and the American Heart Association echoed the companies' assurances and urged patients on Vytorin not to panic after a major test of Vytorin was released on Jan 14. But their stands have drawn criticism from congressional investigators and others because both groups take in substantial sums from pharmaceutical firms.

I'm not going to comment further on this other than to say "that sounds familiar", as the conflict of interest issue affecting medical professional societies has been well addressed by my Healthcare Renewal colleagues.

I will, however, comment on this:

W. Douglas Weaver, president-elect of the cardiologists, echoed those concerns. "We really had huge numbers of patients calling physicians' offices and not knowing how to interpret this information," Weaver said. "People were discontinuing statins because of the confusion."

The unstated but not-so-subtle implication (to those who understand marketing and "spin") appears to be that the big, bad, "anti-pharma" zealots and their allies in the media have gotten the poor public all confused, and the public is stopping their lifesaving meds as a result.

Having been involved in drug nomenclature activities at Merck as well as being familiar with the work of groups such as the Institute for Safe Medication Practices, one major goal in drug naming is to prevent confusion regarding the drug's nature and purpose. One creates drug names to assure that one drug is not confused for another, by healthcare professionals, patients, and others. Information scientists and others work very hard to select names for drugs that do not "resemble" others in spelling, phonetics, etc.

Now, just who is responsible for the confusion among patients "discontinuing statins because of the confusion?"

It seems to me the brainiacs who came up with the marketing scheme of giving a combination drug consisting of a newly-generic drug and a newly-approved one an entirely new name to milk more income out of a drug going generic -- and effectively discourage doctors/patients from simply prescribing/taking two pills (the generic and the new one) -- are largely responsible.

How many patients really understand that their wonder drug has two parts, one old, one new, that they could purchase and take separately likely for less cost than the combination, and that only the "new" part has come under scrutiny? How many understand that if the statin part of the new combination drug doesn't agree with them, they would have to discard the drug instead of simply replacing the statin? In addition, do busy general practice physicians understand this? One wonders.

It therefore seems the marketing folks as well as the drug naming approval organizations and the FDA carry significant blame for the "confusion." Perhaps this is a case of the unexpected (or should I say the predictable but undesired?) happening that provides evidence drug combinations should not be given snappy new names or approved as expensive "new" drugs.

Finally, I cannot but think it ironic that just as VIOXX and other similar drugs may have caused platelets and/or blood vessel walls to become more "sticky" and create vascular side effects, so ezetimibe might cause cholesterol and/or blood vessels to be more "sticky" for reasons not yet understood and negate some of the cholesterol lowering effects. It would be ironic indeed, as the newspaper article suggests by the observation "the combination drug failed to provide any benefit and even performed slightly worse than Zocor alone", if long term studies show ezetimibe to create more harm than good.

However, clinicians, the company and the regulators should be prepared if this occurs to get the data out ASAP when it is available fron ongoing studies - low morale or not.

-- SS