Are Drug Makers Unethical, Or Are FDA Rules At Fault?

Investor's Business Daily ^ | Monday, May 13, 2002 | MERRILL MATTHEWS JR.

[purplegirl]

Several recent news stories have raised concerns about two pharmaceutical manufacturers releasing new versions of two of the most popular prescription drugs in the country: Claritin and Prilosec.

Schering-Plough's (SGP) best seller Claritin goes off patent at the end of this year. As a result, drug companies that produce generic drugs, which are copies of a brand-name drug but usually cost substantially less, can begin to sell their generic versions.

Similarly, AstraZeneca (AZN) is replacing its blockbuster drug Prilosec with its new drug Nexium.

Some medical professionals have criticized Schering-Plough and AstraZeneca for not proving in clinical trials that their new drugs are superior to their predecessors.

Not being a medical doctor, I cannot comment on the merits, if any, of Clarinex over Claritin or Nexium over Prilosec. Having served voluntarily for 10 years on a medical school's institutional review board for human experimentation, which oversees the research at the medical school, I can comment on the clinical trials.

What FDA Wants

There is a good explanation why Schering-Plough compared its Clarinex to a placebo (an inactive substance) in clinical trials rather than Claritin: That is what the Food and Drug Administration wants.

The FDA's drug-approval process requires new drugs to be safe and more effective than placebos, not more effective than existing drugs.

Determining which drugs are the most effective is usually left to doctors' discretion - as it should be.

There is, in fact, a growing debate over whether the FDA's clinical preference is ethical. Many medical ethicists believe that clinical trials should compare a new drug to the standard of care (i.e., the drug most doctors would prescribe), especially in cases where use of a placebo could result in harm to the patient.

Manic Mandates

Take, for example, mental illnesses such as schizophrenia or manic-depressive disorder. A clinical trial designed to test a new drug to treat these conditions would, in most cases, require the patients to cease use of any drugs they are currently taking, perhaps for a few weeks.

The research participants might then be randomly placed in two groups (sometimes more): One would take the new drug and the other would take a placebo. Neither the patients nor their doctors would know whether they were getting the active drug or placebo.

Is it ethical to let patients with a serious mental illness go eight to 12 weeks without any active drug to control their condition, considering such people can not only be a threat to themselves but to others?

Of course, Schering-Plough could decide to compare Claritin to Clarinex anyway, and some do that in what is known as a "post-marketing" study, i.e., after the drug has been approved and is on the market.

But should we really expect drug companies to throw more money into clinical trials than they have to?

"Phase III" trials, in which a new drug is compared to a placebo, often include 2,000 to 3,000 patients at 20 to 30 academic medical centers around the country.

You think your visit to the doctor is expensive? Imagine how much it costs to have hundreds of doctors - plus nurses and other support staff and the medical facilities - seeing thousands of patients over several months or even years. A drug company should be forgiven for not wanting to put another $100 million dollars or so into the process.

Schering-Plough has also been criticized for releasing its new drug Clarinex for a lower price than the one it will succeed.

When any company releases a "new and improved" version of a product, most of us have a lingering suspicion that the only thing really new is a higher price.

However, increasing competition is forcing drug companies to keep some prices lower. For example, after the 1987 release of the new generation of antidepressants such as Prozac, the "launch price" of the next six competitor drugs was between 7% and 45% less than the original. Why? Competitors were hoping to gain market share over a more established drug.

Drug companies have little control over the drug approval process, so criticizing them when they are playing by the rules doesn't make much sense. As for whether one drug is better than another, patients, in consultation with their physicians, should be the ones to make that call.

Merrill Matthews Jr., Ph.D., is a visiting scholar with the Institute for Policy Innovation and director of the Council for Affordable Health Insurance.

[Florida SunGod]

Oh I really shouldn't get started on this but here goes: I worked at the largest contract research organization (CRO) in the United States from 1995-1996 (13 months to be exact) and discovered they were a tragedy just waiting to happen. Going up the chain of command was futile and I even addressed my concerns to the parent company in Montreal, Canada. I resigned in protest and they thought that was the end of it. Wrong. I knew at some point they would screw up and kill someone and I would come forward with the proof that it was not a random accident but a result of their immoral and unethical methodology. Well it didn't turn out quite that way. In 1997 I was informed they were going to be showcased on the tv show EXTRA and I contacted EXTRA and appeared on the program as a whistleblower, for lack of a better term. Then I turned them into the FDA. It resulted in a 3 year investigation and the FDA lying IN PRINT to cover for this firm. In lieu of FDA action (the FDA even lied about their findings, I know: I was able to obtain the medical records of the number of people this corporate criminal made severely sick...) I drove the company out of business myself. It took me 4 years and cost me in excess of $25,000 of my own funds, 4,000-5,000 letters and emails to every conceivable organization and finally the firm's clients but I put them out of business. Their facility is now for sale. They were sold and then closed their facility here and it was the largest of its kind in the UNited States. The new owner gave conflicting reasons for the closure. I made local newspapers 4x over it and a national newsletter but beyond that no news organization wanted to touch it. Canadian Broadcasting Corporation tracked me down a year ago and wanted to do a story, but suddenly dropped it just like all the others did. I wrote a book but have been unable to find a publisher willing to touch it. The FDA is the puppet of the big pharmaceutical firms and it is cheaper for the drug developers to put knowingly bad drugs on the market than to test them properly. it's all about greed. What they make selling the drug more than offsets any settlement they MAY have to pay 10 or 20 years later (for deaths, side effects, illness, etc). My only satisfaction was in knowing I put one criminal firm out of business but there are 10 more to take its place... If you would like more information go to the web site for Public Citizen Health Research Group and you will see how serious a problem it is in the industry.

[tacticalogic]

Are Drug Makers Unethical, Or Are FDA Rules At Fault?

Considering that the bureaucrats at the FDA work hand-in-glove with the lobbyists from the pharmaceutical industry to develop their regulations, is this really an either-or question?

[Eugene Tackleberry]

I don't really have an opinion on this issue, but this article's conclusion seems to me illogical: The author says, (1) It is too expensive for a pharmaceutical company to compare effectiveness of a new drug with the old drug. Therefore, (2)A doctor, in consultation with the patient, should determine if the new drug is more effective than the old drug. So my question is: If there are no studies of whether the new drug is more effective, how the heck are the individual doctors supposed to know? Any experimenting a doctor does is not going to be a double-blind, properly run study. Furthermore, an individual doctor's experience with his/her patients is not going to include enough patients for the results to be statistically significant, . I don't know what the answer is, but this author's solution is not it.

[mountaineer]

Canadian Broadcasting Corporation tracked me down a year ago and wanted to do a story, but suddenly dropped it just like all the others did. I wrote a book but have been unable to find a publisher willing to touch it.

Don't worry, you're not paranoid. They really are all out to get you.

[FairWitness]

I drove the company out of business myself.

Since they are now out of business I assume it would be safe to name them. Who were they?

[FairWitness]

I even addressed my concerns to the parent company in Montreal, Canada.

Follow up to #6: I'll take a guess that "the parent company in Montreal" you are referring to is MDS Pharma Services, formerly Phoenix International. I probably ought to know which company you are referring to that went out of business, but my memory is not working. I ask out of professional curiousity. I placed about $5-6 million dollars in contracts, in $10,000 - $50,000 chunks, during the period of 1996-2001 (am now retired), to a number of contract labs. My areas was largely preclinical, whereas you seem to be referring to human clinical trials. I received a lot of attention from Phoenix as they were trying to get some of the business I was responsible for, but never was convinced they could do the job any better than the companies I was working with.

[self_evident]

I wrote a book but have been unable to find a publisher willing to touch it.

Well, that's not a good sign. Do you think it is because they are afraid, or do they think it just won't sell?

There is plenty of room for abuse in the pharm. business. But like with anything in a free society, you get the bad that comes with the good. I would guess that the vast majority of people benefit. And there is a difference between greed and profits. Profits finance research. Without profits, there will be no private research. In short, it sounds like you may have found a criminal enterprise, but you are condemning the entire industry for the crimes of one.

[Al B.]

There is, in fact, a growing debate over whether the FDA's clinical preference is ethical. Many medical ethicists believe that clinical trials should compare a new drug to the standard of care (i.e., the drug most doctors would prescribe), especially in cases where use of a placebo could result in harm to the patient.

I don't know how fierce this debate is across the board in medicine, but it's raging in psychiatry.  Why?  Maybe not for the reasons they so piously claim.

In a recent study of the FDA's entire clinical trial database for antidepressants over a 12-yr. period, it was found that antidepressants only marginally exceeded placebo in efficacy (41% improvement in depression symptoms for SSRIs vs. 31% for placebo in a database of 8,731 patients).  In fact, most patients in the trials showed no significant improvement at all no matter what they took.

See the FR thread, Against Depression, a Sugar Pill Is Hard to Beat for more on this.

Maybe, just maybe the industry wants to put a stop to bad news like this raining on their parade.

Psychiatry is a haven for product misrepresentation and crummy science.  Removing placebo-controlled trials from the drug approval process would take away the last vestiges of restraints on these people. They'll declare everything from nail-biting to nose-picking a mental disorder and sell anything to everybody.

[Al B.]

To clarify what I said in the post above: In the FDA study 41% of the patients on SSRIs showed significant improvement in depression symptoms vs. 31% for placebo. That's what I was trying to say.

[Free the USA]

Check the Bump List folders for articles related to and descriptions of the above topic(s) or for other topics of interest.

[Florida SunGod]

Idiots like you make posting comments a waste of time.

[Florida SunGod]

Peter Lurie of Public Citizen pointed out to me that my concerns, while focused on a single CRO, are not necessarily unique and are a widespread problem in the industry at large. He also pointed out to me that the problems I encountered with the FDA made Public Citizen take a hard look at CROs across the board. And it was Public Citizen who referred Canadian Broadcasting Corporation to contact me.

[Florida SunGod]

You are correct, it was PILS. They were sold to MDS/Harris after I contacted the home office of PILS in Montreal with an ultimatum (after they had invited me to "take a 2nd look" at their Cincinnati operation in late 1999 only to answer my acceptance of same with "No comment") My ultimatum being: PROVE to me you have cleaned up your operation or I start sending the newspaper stories and 175 page FDA report to your clients. I started contacting clients directly, PILS was sold about 2 months later and the new owner MDS, closed the Cincinnati facility against all logic other than their inability to maintain an operation I was determined to continue spreading the word about as it continued to employ some of the same people responsible for the criminal wrongdoing when I worked there. The FDA lied to protect this firm and I have proof of it. The FDA lied to me to prevent me from obtaining records through FOI requests. And FYI, I obtained medical records. In one instance a subject had suffered a seizure but when the paramedics came to take him to the hospital a PILS technician injected him with something and later denied it was done. Clearing evidence of another drug being tested? Was PILS working for the feds? Funny they went from the verge of bankruptcy when I quit in November 1996 only to grow to 4th largest CRO in the world within a few months of turning them into the FDA. Conspiracy minded? No. Just the facts...

[FairWitness]

Thanks for the info. As I said, I did not personally work with Phoenix or subsidiaries.

[mountaineer]

Coming from you, that means a whole lot.

[self_evident]

Peter Lurie of Public Citizen pointed out to me that my concerns, while focused on a single CRO, are not necessarily unique and are a widespread problem in the industry at large.

Well, if it's widespread then your concerns are not unique. That's pretty much the definition of widespread.

And I checked out Public Citizen. All hype about radioactive storage, car safety, and VERY VERY big on CFR. No science to be seen. Basically a typical left-wing, conservative bashing organization. Not something you should reference for support.

[Florida SunGod]

So if someone attempts to reform big business or points out wrongs and "rocks the boat" you automatically label that person a "leftist"? I am by far no leftist. If it were not for people like Ralph Nader we would be living in a society completely dominated and controlled by big business. We already do, but awareness is key to maintaining freedom from corporate control of our lives. When you remove your head from the sand you might just be grateful that some people are not willing to accept the status quo. Some people can think for themselves and not have their views dictated to them simply to avoid being labeled...

[Florida SunGod]

No one else would work with them either when I was finished with them.

[Florida SunGod]

Do you know me? Do you know anything about me? No you don't and you have no idea the level and magnitude of scandal about which I am commenting. Making snied remarks makes you look dumb, not me. Have you seen the medical records of the people they made sick? I have them. Have an explanation why the City of Cincinnati LOST all 911 records for 1996? (when PILS had the most 911 emergency runs to their facility) No. Neither did the City of Cincinnati when it was a news story I broke. Convenient for PILS to say the least. So you can snicker and make comments about me like I'm some kind of paranoid whacko all you want. Facts don't lie.