I bowed out of the debate on generic drugs with my article in The Island of 22nd April 2008 under the title ‘The official policy is flawed, and needs corrective surgery!’ I mentioned therein that I entered the debate initially on behalf of patients who found themselves trapped in the battle that flared up between Dr. D.P.A. Atukorale on the one side and Prof. Carlo Fonseka and Dr. K. Balabsubramaniam on the other, and that I continued to participate in the debate due to my interest in public policy analysis. I now make (hopefully) a brief return for reasons that should be clear from what follows.

In my article of 22nd April, I raised two issues that I thought should receive the attention of policy makers before finalizing the National Medicinal Drug Policy or NMDP, based on the material that had surfaced during the debate. To quote from the concluding paragraph, I said:

"To sum up, the two main concerns that need to be addressed by the policy makers are as follows:

Now that the Minister of Health has fixed a cut-off date for the finalization of the National Drug Policy (The Island online edition of 14th July), I felt it necessary to draw the attention of policy makers to the two matters raised by me, if they have not already taken note of them. I have tried my best to keep track of the debate since taking leave of it even though I am away from the island since mid-June, and do not recall seeing any expression of disagreement with what I have proposed, by any of the three leading spokespersons for the NMDP who participated in this debate (Prof. Carlo Fonseka, Dr.K Balasubramaniam and Dr. K. Weerasuriya).

During the past few months, I have made it a point to read whatever material that came my way, which has some relevance to the issues that surfaced during the debate. Hence, it was no surprise that a book entitled ‘The Real Drug Abusers’ which I found in the library of the university in which my daughter and son-in law are teaching here in the United States caught my attention, and I got my daughter to borrow it for me to read.

Fred Leavitt, the author of the book, has a Ph.D in psychopharmacology from the University of Michigan, had a postdoctoral fellowship in Berkeley, and has taught at Carl State University in Hayward. He has also been a visiting professor at universities in Kenya, Canada, New Zealand, England, the Netherlands and Turkey. The very first chapter in Prof. Levitt’s book is titled ‘A Significant Portion of Medical Research Cannot be Trusted’ and carries a separate section on The Food and Drug Administration (FDA) of the United States. This is how he commences this section: "The FDA was established to protect consumers against dangerous and ineffective drugs, but FDA approval does not guarantee effectiveness and most certainly does not guarantee safety. The human studies conducted to meet FDA approval typically last four to six weeks. Imagine if the dangers of cigarettes had been evaluated only after six weeks of tests. Furthermore, because most tests are conducted under the auspices of drug companies, adverse effects are often overlooked or minimized."

Leavitt proceeds to point out that the number of ‘subjects’ selected for the tests often differ in important ways from the population that will ultimately receive the drugs, and the number of subjects rarely exceed 4000, which is too small to reliably detect rare adverse reactions. He says that "an estimated 51% of drugs produce adverse reactions not detected until after they have been approved…. Between 1997 and 2000, ten drugs that had been taken by about twenty-two million Americans were withdrawn for safety reasons. Top selling anti-inflammatory drug bromfenac and antihistamine terfenadine were withdrawn between 1997 and 1998 after being prescribed to millions. Each caused serious side effects and deaths."

According to him, the FDA is woefully short staffed. But, that is not all! "Problems with the FDA go deeper than insufficient staff and inadequate mechanisms for reporting adverse defects. FDA committees that evaluate the safety of substances are often packed with industry-funded scientists." He describes a number of instances, too numerous to mention here, where the interests of the drug industry have prevailed over the public interest as a consequence. Here is a stunning example, which may appear unbelievable!

I quote: "Patients in clinical studies who took the diabetes troglitazone (Rezulin) suffered severe liver damage. Executives at Warner-Lambert, the drug’s manufacturer, claimed that the risk was trivial. The FDA medical officer assigned to evaluate Rezulin, John Gueriguian, disagreed and expressed concern about its potential toxicities. His boss acted promptly – he phoned a senior manager at Warner-Lambert and said that he would try to resolve the problem. If not, he promised he would remove Gueriguian from the review of Rezulin. Shortly afterward, Gueriguian was removed and FDA staff withheld the existence of his review from the advisory committee. Company and FDA documents show that FDA officials provided Warner-Lambert with inside information and favors throughout the development and marketing of Rezulin. Rezulin was approved in December 1996 and withdrawn in March 2000, more than two years later than in Britain, after having been cited as the suspect in 391 deaths–and having generated $2.1 billion in sales. Gueriguian commented, "The people in charge don’t say, ‘Should we approve this drug?’ They say, ‘Hey, how can we get this drug approved?’"

Here’s one more! " In 1993, the FDA official in charge of evaluating the drug cisapride (Propulsid) for approval was not a cardiac specialist He reviewed studies showing that forty-eight patients who had taken Propulsid for easing nighttime heartburn had developed abnormal electro cardiogram patterns and eight young children given Propulsid had died. Still, he recommended approval. Within two years, adverse reaction reports implicated Propulsid in several deaths. Scientists employed by the manufacturer, a subsidiary of Johnson & Johnson Co., argued that the deaths were due to other causes. They agreed to add a new safety label. The manufacturer donated money to the North American Society for Pediatric Gastroenterology and Nutrition, and Propulsid received the stamp of approval for treating gastric reflux in infants. Gastric reflux is a minor disorder that infants usually outgrow by the end of their first year. Safe, inexpensive, and effective therapies existed, but Propulsid became a popular treatment choice. Several children died. Several years after approval, in 2000, Propulsid was finally taken off the market as a normally prescribed drug. It had generated U.S. sales of $ 2.5 billion and is suspected of killing more than three hundred people."

Leavitt provides many more examples to support his thesis. While I was half-way through his book, a copy of the Reader’s Digest (April 2008 issue) lying around in my daughter’s living room caught my attention due to a striking blurb in red on its cover page which said "CAN WE TRUST THE FDA? Must–read special report". I could not help leaving Leavitt aside and reading through this report with even greater interest as the Reader’s Digest (RD) would be available more readily for Sri Lankan readers than Leavitt’s book.

The RD special report begins with the following words: "Recent headlines have uncovered one shocking lapse after another at the Federal Drug Administration: A popular diabetes drug can sharply increase the risk of a heart attack, a finding the agency knew but took two years to reveal. An FDA–approved antibiotic can destroy your liver in just five days. ……………..Many of the nation’s leading doctors, scientists and lawmakers now agree that the FDA is in crisis. Lurching from one disaster to another, the 102-year old agency learns of dangers too late and then moves too slowly to remedy them. Insiders say that it’s woefully underfunded, dangerously understaffed and fractured by bitter internal tensions. Instead of depending on the FDA, Americans are doubting it – and for good reason."

The Reader’s Digest (RD) refers to what it calls "a chilling new report commissioned by the FDA’s own advisory Science Board" which describes it as an organization nearly out of control. That’s not all! The respected Institute of Medicine, created in 1970 by the National Academy of Sciences had recently labeled the FDA’s drug branch as dysfunctional, "saying it muzzles scientific dissent, inadequately monitors drug safety and relies too heavily on drug company dollars." According to the RD report, industry dollars now pay for more than half of the FDA’s drug–review budget; and in five years that proportion is expected to jump to 70%.

RD says that a former drug reviewer of the FDA, Dr.David Ross, has said that when drug reviewers often tell their FDA supervisors that a drug does not work or has a major safety problem, "managers come up with contrived reasons to approve the drug anyway". According to Ross, the standards of safety and efficacy have slipped away to the point that the "drug reviewers can end up approving almost anything".

The story reported in the RD about ‘Ketek’ an anti-biotic meant for respiratory tract infections which had been approved by the FDA based on fake safety data submitted by the manufacturer, reads like a horror story! Dr.David Ross, the FDA drug reviewer referred to above, who had unsuccessfully tried to stop Ketek’s approval has said: "The company submitted fabricated data, the FDA knew it, and they approved the drug anyway."

The RD report says: "Six million Americans have now used the drug, including hundreds of infants in a clinical trial designed to test Ketek’s effectiveness against ear infections". Another FDA scientist Dr. Rosemary Johann-Liang had protested in a memo addressed to her superiors asking "How does one justify balancing the risk of fatal liver failure against one day less of ear pain?" - to no avail. Most ear infections, she has said clear up in a few days on their own! There is more to the Ketek drama in that the physician (a lady) who allegedly forged scores of signatures in the study is now in a federal prison, and another physician was arrested at his home shortly after the study ended with a bag of cocaine, waving a loaded gun at imaginary people! Sounds more like a thriller from the drug underworld, doesn’t it? The saga has apparently not ended and more thrills are on the way! In the meantime, "Ketek has now been linked to 18 deaths and at least 134 cases of liver damage, according to an independent analysis using FDA data. The real toll, some researchers say, may be far greater" says the Reader’s Digest.

The RD special report points out that FDA’s advisory boards, which vote on drugs and devices, are intended to represent a broad spectrum of physicians, researchers and patient advocates – not stockholders. But a study published in 2006 found that in 22% of advisory board meetings more than half the members had direct financial interests in the companies whose medical products they evaluated, or their rivals. According to the report, many agency staffers have said that they feel pressure to soft-pedal product dangers. In a poll of 1,000 FDA scientists conducted in 2006, 20% said FDA decision makers had asked them explicitly "to provide incomplete, inaccurate or misleading information to the public, regulated industry, media or government officials. And 40% said they could not publicly express concerns about public health "without fear of retaliation".

Thus we see the Reader’s Digest special report confirming Leavitt’s findings, and I have no doubt that my good friend Carlo will gleefully wave Marcia Angell’s book (which he is very fond of quoting from and, I must confess, I am yet to read) at us, and say this is what he has always been saying about the ‘good Samaritans’ of the drug industry who hold the rest of the community to ransom, contrary to what their apologists would like to make us believe!

I had hardly recovered from the shock of reading the revelations made by Prof. Leavitt and the Reader’s Digest when I happened to read Dr. Mahinda de Silva’s article in The Island of 7th July where he describes the FDA as "an outstanding model of a drug regulatory authority" obviously for us to follow. Coming from someone who had been a medical practitioner in US for 20 years or so, it was indeed unbelievable! Surely, both Prof. Fred Leavitt and the Reader’s Digest cannot be wrong as they have fully substantiated what they have said well knowing that they can be hauled up before court, if otherwise, and the drug industry is not short of funds to employ the best available lawyers!

Let me conclude this essay by pointing out that we need to think beyond the American model in working out a suitable structure and working arrangements for own drug regulatory authority as the success or the failure of the proposed National Medicinal Drug Policy will largely depend on the efficacy, efficiency and, above all, integrity of this all important body. It is here that ardent supporters of the NMDP who have participated in this debate and have the ear of the Minister and other policy makers have a major role to play, unless we want the remedy to end up worse than the disease!

Postscript

Here is another comment about the FDA which I read after completing the above text. It is by Joe & Teresa Graedon (best-selling authors of the People’s Pharmacy) in the recent Signet/Penguin publication ‘Best Choices from The People’s Pharmacy’:

"The FDA routinely approves medications that can trigger dangerous, if not deadly, reactions. The best known example of this came to light in 2004 when Vioxx (rofecoxib) was taken off the market by the manufacturer. Renowned cardiologist Eric Topol, MD, was provost at the Cleveland Clinic Lerner College of Medicine. In an editorial in the New England Journal of Medicine, Dr. Topol estimated that as many as 160,000 people may have suffered heart attacks or strokes while taking Vioxx. FDA safety officer David Graham, MD, estimated that 30,000 to 40,000 people may have died as a consequence.

In Senate hearings, Dr. Graham had declared, "I would argue that the FDA as currently configured is incapable of protecting America against another Vioxx. We are virtually defenseless. It is important that this committee and the American people understand that what has happened with Vioxx is really a symptom of something far more dangerous to the safety of the American people. Simply put, FDA and its center for Drug Evaluation and Research are broken."