Why statins should not be widely prescribed, or the difference between relative and absolute risk

In The New York Times yesterday, Duff Wilson did a great job of explaining why many medical experts question the growing use of cholesterol-lowering statins in people without heart problems. He reported on new studies showing the risks of otherwise healthy people taking statins, and he exposed the huge conflict of interest by the scientist who led the study that enabled AstraZeneca to win FDA approval for marketing its statin, Crestor, to people without heart problems. (The scientist, Dr. Paul Ridker, a cardiologist at Harvard and Brigham and Women's Hospital, receives lucrative royalties on the test used in the study to determine whether people without visible heart problems might benefit from Crestor, There is much dispute over whether test itself, which measures an elevated level of inflammation in the body, indicates underlying heart problems).

Wilson also performed another estimable service: he highlighted the difference between relative risk and absolute risk. Relative risk is the statistical difference in outcome between a control group and a group taking an active drug in a study, whereas absolute risk is the actual number of people who might actually benefit from the drug. Most randomized clinical trials only report relative risk, which often inflates the benefits of the drug being studied.

So, as Wilson explained:

The rate of heart attacks, for example, was 0.37 percent, or 68 patients out of 8,901 who took a sugar pill. Among the Crestor patients it was 0.17 percent, or 31 patients. That 55 percent relative difference between the two groups translates to only 0.2 percentage points in absolute terms — or 2 people out of 1,000.

And then he goes on to put the difference into even clearer context:

Stated another way, 500 people would need to be treated with Crestor for a year to avoid one usually survivable heart attack. "That’s statistically significant but not clinically significant,” said Dr. Steven W. Seiden, a cardiologist in Rockville Centre, N.Y., who is one of many practicing cardiologists closely following the issue.

Well done, Duff!

On another note, I just wanted to let readers know that I am taking a hiatus from weekly blogging. I may still wade in now and then to blog about a timely issue (when I can't resist), but it's time to turn my attention to another project.

Shining the light on drug company shell games

First the good news: The Physician Payment Sunshine Act is now law, signed by President Obama as part of the health care bill overhaul. Starting in 2012, drug and medical device companies must report all consulting, speaking and other payments to doctors and teaching hospitals in excess of $100 annually to the federal Department of Health and Human Services, which will post the payments on a public website. This is an important first step toward making transparent the pervasive financial ties between doctors who are studying or promoting specific drugs and medical devices and the companies that manufacture these products.

There is one significant loophole in the law: according to the final provisions, payments related to clinical trials or product development agreements for new products are allowed a publication delay of four years or until product approval, whichever comes first. So if a particular doctor is researching a drug that has not yet been approved for a specific condition, we will have to wait four years to find out whether he or she is on the drug company's payroll. But at least the disclosure will eventually see the light of day, and patients who are prescribed the drug in question can seek a second opinion from a doctor who is not on the drug firm's payroll and whose medical judgment can be trusted.

The Physician Payment Sunshine Act, however, only goes so far. While it covers doctors and teaching hospitals, it does not extend to all the advocacy groups and professional organizations that have substantial influence on over how particular illnesses are treated. For example, as I reported, the National Alliance for the Mentally Ill (NAMI), the most powerful advocacy group for people with mental illness, received millions of dollars in funding from drug companies for years -- a payola that no doubt spurred this group's embrace of potent psychoactive drugs over alternative methods of treating mental illness.

And now, in the current Psychiatric Times, two Massachusetts researchers tear the veil off efforts by the American Psychiatric Association (APA) to hide industry funding of its two philanthropic arms -- the American Psychiatric Foundation (APF) and the American Psychiatric Institute for Research and Education (APIRE). As Lisa Cosgrove and Harold Burszstajn report: "While the APA recently announced it would phase out the visibly industry-supported educational programs, the organization has remained curiously silent about acknowledging and monitoring industry funding" of APF and APIRE.

Why does this matter? Because the APA is not only a powerful lobbying force in Washington and the premier trade group for America's psychiatrists but it also publishes the DSM, the diagnostic bible of psychiatry, that largely determines how psychiatrists treat mental illness. As I've blogged about before, the proposed DSM-V further broadens the categories of various disorders, which will have the net effect of creating profitable new markets for drug companies.

Hence, Cosgrove, a clinical psychologist at the University of Massachusetts, and Bursztajn, a psychiatrist at Beth Israel Hospital and Harvard Medical School, decided that the public has a right to know about any hidden financial ties between the APA and the pharmaceutical industry. So they investigated and found that the boards of both APF and APIRE were stuffed with high-level executives from companies that make drugs recommended by the APA and with psychiatrists who have financial ties to these drug companies. They discovered, for example, that nine of 16 board members of APIRE had industry ties.

Yet neither organization requires disclosure of financial conflicts of interest. Nor is there much information as to how much money Big Pharma is giving these organizations. In their Psychiatric Times piece, Cosgrove and Bursztajn ask the valid question:

Has industry removed the transparent and visible shell of professional education programs and replaced it with the more opaque shells of foundations such as APF and APIRE?

The authors go onto recommend that individuals serving on APF and APIRE's boards post disclosure statements and that the total amount of industry funding given to these organizations be posted. They also suggest that the boards of both groups be reorganized to more genuinely reflect a patient-centered focus. They conclude:

Steps need to be taken to lift the cloak of silence that surrounds the issue of indirect or covert ties exerting undue industry influence.

I couldn't have said it better.

Why tort reform isn't on the table: hard lessons about special interest money in Washington

Every semester, I do an in-class competition to show my students the power of the Web in digging up data for stories. I separate them into groups and ask them to find the answers to specific questions about current sociopolitical trends. Two questions I always ask are: one, what are the top industries in terms of campaign contributions to Congress and two, which are the top industry spenders on lobbying Congressional and federal officials. (These are two very different ways of influencing policy decisions).

The answers this year were instructive, particularly in the light of the ongoing battle to pass a health care bill.

Not surprisingly, the pharmaceutical/health products industry topped the list of industries spending millions of dollars to sway the opinion of Congressional and executive policy makers, according to Center for Responsive Politics, a nonpartisan, nonprofit research organization that tracks money in U.S. politics. This industry, which includes Big Pharma, biotech and the medical device industry, spent $263 million in 2009, far ahead of the second (business associations), third (oil and gas) and the fourth highest (insurance companies) spenders on the list. This ranking comes as no surprise, since the pharma/health industry has dominated the list of big spenders on lobbying for more than a decade, which goes a long way toward explaining why Big Pharma almost always gets its way in Congress and with the FDA as well.

What may come as more of a surprise is the industry that of late has topped the list of big spenders on Congressional campaign contributions: lawyers and law firms. In the 2009-2010 election cycle, lawyers gave Congress $27 million and the top recipient of their largesse was none other than Harry Reid, the Majority Leader for Democrats in the Senate. In the 2008-2009 election cycle, Barack Obama was the top recipient of their money, and in 2007, it was Hillary Clinton, then considered the front runner as the Democratic presidential candidate, again according to the Center for Responsive Politics, which culls its data from government records.

Such over-the-top spending explains why tort reform has been consistently excluded from each version of the health care bill, despite the fact that it's a favorite cause of Congressional Republicans. There's an ongoing debate over just how much money tort reform, or putting caps on the amount of money plaintiffs and their attorneys can reap from malpractice lawsuits, would actually save. For example, it's debatable whether tort reform would generate much savings in malpractice insurance, but there's no question that if doctors were less afraid of getting sued for big bucks, they might order fewer tests and procedures for patients and that could generate considerable savings, particularly if it was linked with real changes in the way doctors are reimbursed for care (i.e. being paid by salary rather than fee for service).

But what I haven't understood until now is why the Democrats haven't been using tort reform as a bargaining chip to bring some moderate Republicans into the fold on the health care bill.

Now that I (and my students) see how much big money lawyers have been throwing at Congress and our current President, I understand why tort reform is not on the table. And that's a damn shame. If capping monetary damages in medical malpractice suits were part of health care reform, some Republicans might just break rank and vote for it.

Instead, we see special interests once again calling the shots. No wonder the American public is, as Neal Gabler says in The Boston Globe today, so enervated and apathetic.

Financial conflicts and other problems with the proposed DSM-V

I have hesitated to weigh in on the debate raging over the proposed changes to the DSM-V (psychiatry's diagnostic bible), in large part because others more literate in psychiatric minutiae have already done so. To wit: Dr. Allen Frances in the Psychiatric Times, Dr. Edward Shorter in the The Wall Street Journal, and Dr. Daniel Carlat on his blog.

All three of these experts agree that the DSM-V (which, like previous DSMs, was created by psychiatrists appointed by the American Psychiatric Association) is dangerously broadening the categories of various disorders, which will have the net effect of creating profitable new markets for drug companies. As Frances, the chair of the previous DSM-IV task force, puts it:

DSM5 would create tens of millions of newly misidentified false positive “patients,” thus greatly exacerbating the problems caused already by an overly inclusive DSM4. There would be massive over-treatment with medications that are unnecessary, expensive, and often quite harmful. DSM5 appears to be promoting what we have most feared--the inclusion of many normal variants [like grief] under the rubric of mental illness, with the result that the core concept of "mental disorder" is greatly undermined.

However, the pundits seem to disagree when it comes to one particular change: subsuming Asperger's and other similar disorders under the broadened category of autistic spectrum disorders. While Shorter and Carlat think it's a good idea, Frances argues that this consolidation presents serious problems -- see again his Psychiatric Times essay. At a dinner party last night, I heard similar concerns from several mental health professionals, including allegations that the change may have been pushed for less than noble reasons -- i.e. financial gain.

But before I get to the possible conflict of interest here, let me enumerate their larger concerns:

1. There seems to be no scientific basis for subsuming Asperger's syndrome under the tent of autistic spectrum disorders.
2. Many children and adolescents with Asperger's benefit from a specially constructed type of environment (with special supports at school to bolster the social skills they lack). If these children are subsumed under the autism tent, there may be less emphasis on constructing such supportive environments and they may be more likely to be prescribed powerful anti-psychotic drugs like Abilify and Risperdal that are now approved for use with autism. Forget the fact that these drugs have significant side effects. If this happens, many Asperger's patients will not get the specialized attention they need.
3. There may be a temptation to diagnose children with mild autism as having Asperger's, thus undercutting the reality that while some people with Asperger's are highly functioning individuals, many others are severely disabled. As a result, people with severe Asperger's may also not receive the intensive care they need.

Now to the potential conflict of interest with the proposed change. As it turns out, one of the members of the DSM-V task force is Catherine Lord, a professor at the University of Michigan, who gets big royalties from a diagnostic test she helped develop (known as ADOS) that is used to diagnose autistic spectrum disorders in children. As it turns out, the subcategories for the ADOS test fit very neatly into the new criteria proposed for the autistic spectrum disorders in the DSM-V.

Now, according to an APA disclosure report I found online, Lord has agreed not to accept more than $10,000 from "industry sources" each year from the time the DSM-V is approved until its publication (the report says that will be in 2012, but recently the APA agreed to delayed publication of a new DSM until 2013).

What I want to know is: does this agreement include all the royalties Lord currently receives from the ADOS diagnostic test and the expensive bucket of toys that come with it? And if so, what happens after the DSM-V is published when all those royalties start flooding back in?

More importantly, should Lord have been allowed to sit on the DSM-TV task force in the first place and influence major policy changes in psychiatric diagnoses that will affect millions of vulnerable children? I think not.

A few questions for Judith Warner and her editors

The glowing review of Judith Warner's new book, We've Got Issues, in The New York Times this week didn't exactly catch me by surprise -- anyone who has read Warner's guest columns in recent years knows her take on psychiatric drugs -- but it did bewilder me.

Why, I wondered, did the Times choose that particular book to review so prominently in its science section; was it because Warner has such a cozy relationship with the paper, having been a guest columnist for many years?

The reviewer says that Warner "sallied forth to interview all the pushy parents, irresponsible doctors and over-medicated children she could find — and lo, she could barely find any." And that made me wonder just who did Warner actually interview for the book (which, let me admit right off, I have not read). Did she only talk to the parents of children with "issues" and the doctors who prescribed meds for them, as the review makes it sound? If so, she seems to have missed half the story. After all, parents who put their kids on psychoactive drugs and the doctors who prescribed them are probably quite earnest in believing they did the right thing. As a parent myself, I know: it's very hard to admit publicly that you may have done the wrong thing; ditto for the medical profession.

What I want to know is: did Warner bother to interview any of the folks who were forced to take powerful psychoactive drugs as children and grew up to be psychiatric survivors who have since turned to more effective, alternative methods of healing? Did she interview any of the foster children in Florida and other states where these drugs have been used for years as chemical straitjackets to control behavior caused by abuse and neglect? Did she interview the mother of four-year-old Rebecca Riley who was recently convicted of pumping her daughter full of the anti-psychotic drugs that killed her?

Did Warner interview any of the teachers or professors who deal with the detritus of inappropriately medicated children and teenagers every single day?

And where the heck did she get the information that psychiatric drugs help change the structure of the developing brain for the better? I'd like to see the evidence backing up that wild claim.

Finally, I'd like to know who orchestrated Warner's book publicity because it was a stroke of genius to postulate that this woman ever initially believed that children were being over-medicated and then changed her mind after doing the research for her book. Judging from what Warner herself has written over the years, I seriously doubt that claim. But I have to acknowledge: it's a brilliant piece of marketing.

Does aspirin really reduce the risk of breast cancer? We don't know yet...

In my health and science journalism class at Mount Holyoke yesterday, we were talking about all the questions journalists need to ask in deciding whether and how to report on a new medical finding. Two of the key questions that emerged were: 1. did the results come from a randomized clinical trial -- the gold standard of medical research -- or was it an observational study that examines people over time but has no control sample? And 2. did the study actually show cause and effect or just an association?

As it happened, the day's news furnished me with the perfect case example to illustrate the importance of these two questions. A page-one story in The Boston Globe, headlined "Aspirin may combat cancer, study suggests," trumpeted the results of a study published in the Journal of Clinical Oncology. The study in question was not a randomized clinical trial, i.e., it did not randomly compare what happened to one group who was taking the active drug (in this case, aspirin) with a control group who was taking a dummy pill or placebo. It was an observational study of more than 4,000 nurses (in the Nurses Health Study) who were diagnosed with breast cancer between 1976 and 2002, and it compared what happened with those nurses who regularly took aspirin vs those who did not. What the study concluded was that aspirin was associated with a decreased risk of death from breast cancer.

Associated is the key word here. The study did not find a cause and effect relationship, i.e. that the use of aspirin played a central role in reducing the risk of death from breast cancer. It only found an association between those two events (aspirin use and decreased risk of death). As Gary Taubes so eloquently points out in his New York Times magazine article, there can be a myriad of other reasons explaining such an association. There's something, for example, called the healthy volunteer effect. The nurses who took the aspirin in this particular study could simply be healthier and more concerned with staying healthy than the nurses who didn't, which might explain why they had a lower risk of dying from breast cancer. Until a randomized clinical trial is done, we won't know for sure whether it was the aspirin that kept more of the nurses alive or something other yet unidentified reason.

As Taubes notes, long-term prospective studies like the Nurses Health Study were among the first to show what looked to be an association between hormone replacement therapy and a reduced risk of heart disease and cancer (an association, by the way, heavily promoted by Wyeth and other companies that sold such replacement therapies). And we all know where that led us: to the routine prescribing of estrogen/progestin pills for millions of menopausal and postmenopausal women, a practice that significantly increased the risk of breast cancer for many of these women. This cause and effect and the discovery that hormone replacement therapy was not even protective of heart disease was only discovered years later when the federal government finally got around to funding a randomized clinical trial. In the meantime, thousands of women taking replacement therapies developed breast cancer and many died as a result.

Now I'm not saying that taking aspirin could produce a similarly devastating effect. Not at all. I take aspirin regularly myself to ward off bad headaches and I always keep a bottle handy. What I am saying is that the media needs to do a better job of explaining to their readers the difference between studies that find an association and studies that find an actual cause and effect. The Boston Globe article referenced above did not do a very good job of parsing this important difference and as a result, did a serious disservice to its readers.

Suing doctors who use drugs as chemical straitjackets for children

It's true that the drug industry was hard hit last year with some pretty hefty fines for the illegal off-label promotion of drugs -- $1.4 billion against Eli Lilly for its off-label promotion of Zyprexa and $2.3 billion against Pfizer for doing the same with several drugs. But such fines, many say, are still considered the cost of doing business in an industry that raked in close to $300 billion in U.S. drug sales in 2008 (and more in 2009), according to IMS Health Reports.

Now, Alaska attorney Jim Gottstein has proposed a different and potentially more effective approach toward curbing the systemic over-drugging of economically disadvantaged youngsters in this country, a sad reality which I've written about here and here. According to one recent study, children covered by Medicaid are given anti-psychotics such as Zyprexa and Seroquel (which have serious side effects) four times as often as children whose parents have private insurance. These drugs are often prescribed as chemical straitjackets to control children whose parents or foster families are unable to give them the attention and parenting they need. That was certainly the case for four-year-old Rebecca Riley, who died from an overdose of psychoactive drugs prescribed by a psychiatrist at Tufts Medical Center, Kayoko Kifuji.

Gottstein has launched an initiative to sue doctors like Kifuji who blithely prescribe potent drugs that are not approved for use in children. These lawsuits, filed under a federal Qui Tam complaint, would target not only the individual doctors but the hospitals and clinics that employ them and the pharmacies that fill their prescriptions and submit them to Medicaid for reimbursement. It is Gottstein's contention that these prescriptions constitute Medicaid fraud since they are written for uses that are not medically accepted (i.e. off-label). There is legal precedent for this kind of argument. Indeed, the Department of Justice's news release announcing its $2.3 billion settlement with Pfizer says that the drug giant caused false claims to be submitted to government health care programs for uses that were not medically accepted indications. So if the feds can succeed with this kind of argument, why not individual claimants?

Gottstein is planning to discuss his medicaid fraud initiative in a lecture webinar on Feb. 24, sponsored by the International Center for the Study of Psychiatry and Psychology. So if you know of a disadvantaged child who was slapped on drugs he or she didn't need, you might want to listen in.