Controversy over cervical cancer vaccine

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(This article was #26 in Discover Magazine’s top 100 stories of 2007.)

This past year, several countries and at least 24 states in the United States introduced laws to mandate vaccination against cervical cancer for preteen girls. Although the vaccine was initially hailed as a breakthrough, urgent proposals to make it mandatory quickly triggered a backlash. “In the long term,” says Susan Wood, a former director of the FDA Office of Women’s Health, “the rush to get this mandated immediately has done more harm to the issue.”

The FDA approved Merck’s Gardasil vaccine in 2006, after clinical trials showed that it protects against four strains of human papillomavirus (HPV), which together cause about 70 percent of cervical cancers and 90 percent of genital warts. HPV is the most common sexually transmitted virus among Americans (and cervical cancer is the second most common cancer in women worldwide). Because the vaccine doesn’t reverse existing exposure, the CDC recommends it be administered before the age of sexual activity—specifically to girls ages 11 to 12. As for women who already have HPV, two separate studies published in May in the New England Journal of Medicine reported that the vaccine’s effectiveness in preventing cervical lesions dropped to 20 percent or less.

Some conservative groups oppose targeting preteens, arguing that because the virus is sexually transmitted, the vaccine will encourage promiscuity. Meanwhile, bioethicists who are skeptical about compulsory vaccination laws note that all other mandated vaccines protect against diseases easily transmitted in schools. “In my opinion, there’s not a compelling ethical reason [to mandate],” says Richard Zimmerman, professor of family medicine at the University of Pittsburgh. “The ethics is the opposite: to strongly recommend, but not to mandate.”

New vaccine blocks bird flu

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(This article was #12 in Discover Magazine’s top 100 stories of 2007.)

Although avian flu made few headlines in 2007, the virus continued to claim lives in Asia, particularly in Indonesia. The good news is that this year the FDA approved the first bird flu vaccine and announced plans to stockpile it for emergency use during a crisis.

The H5N1 strain of bird flu first appeared in Hong Kong in 1997 and since then has infected more than 330 people, killing more than 200. In 2007, the virus—which normally infects birds and occasionally jumps from birds to humans—affected seven countries, prompting experts to warn that it could gain the ability to jump from person to person and trigger a pandemic.

In April, the FDA approved a two-shot vaccine made by Sanofi Pasteur. In a clinical trial, this vaccine protected 45 percent of the adults who received the highest dose against infection from H5N1. The government said its goal was to stockpile enough doses of the Sanofi vaccine to protect 20 million people as a stopgap measure until a more potent vaccine is available.

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FDA says cold medicine is not for children under 6

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(This article was #18 in Discover Magazine’s top 100 stories of 2007.)

In October, Food and Drug Administration (FDA) advisers recommended against the use of most nonprescription cold and cough medicines for children under age 6, citing the lack of evidence of safety or efficacy in this age group. Prior to the announcement, most manufacturers had already voluntarily restricted sales of medicines formulated for children less than 2 years old.

The FDA review of the medications began after a report by the Centers for Disease Control in January found that, between 2004 and 2005, more than 1,500 children under the age of 2 had wound up in emergency rooms after taking over-the-counter cough and cold medicines. In another development that prompted the review, Baltimore city officials filed a citizen petition with the FDA in March, noting that the remedies do not help children under 6 years of age and may in fact harm them.

There are roughly 800 products on the market containing antihistamines, decongestants, anticough agents, and other chemicals intended to treat colds and coughs in children. Like many pediatric medicines, they have been tested only in adults and are simply packaged to deliver smaller doses to children.

In September, the FDA also required that, by November 2007, drug companies stop making unapproved prescription drugs containing the narcotic cough suppressant hydrocodone for use by children younger than 6. Manufacture of all other unapproved hydrocodone products must halt by December 31.

Male circumcision: A new defense against HIV

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(This article was #15 in Discover Magazine’s top 100 stories of 2007.)

Male circumcision cuts the risk of HIV transmission in men by about 60 percent and should be scaled up in countries hardest hit by the epidemic, the World Health Organization (WHO) announced in March, citing compelling evidence from three large trials in Kenya, Uganda, and South Africa.

Since the 1980s, dozens of smaller studies have suggested that countries with high rates of circumcision, like the Muslim nations of western Africa, have lower rates of AIDS, whereas southern* Africa, where circumcision is rare, has been ravaged by the epidemic. There, a 2006 study suggests, circumcision could prevent about 6 million HIV infections and 3 million deaths over 20 years. Still, the WHO held back its recommendation until 2007, citing the need for randomized clinical trials.

“Circumcision was ignored for ages,” says Daniel Halperin, an AIDS researcher at the Harvard School of Public Health, who laid out the case for circumcision in The Lancet as far back as 1999. “What I mainly criticize the WHO for is that, even with dozens and dozens of powerful studies, they refused to even talk about it.”

Circumcision is thought to prevent infection because the underside of the foreskin is rich in immune cells that are particularly vulnerable to HIV. Small tears in the foreskin during intercourse can also allow the virus to slip into the body.

Circumcision could reduce the odds of an infected man’s transmitting the virus to a female partner by 30 percent or more. For all its benefits, though, the WHO cautions that it should not replace standard methods of prevention like the use of condoms.

Rx for the FDA

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(This article was #5 in Discover Magazine’s top 100 stories of 2007.)

For the Food and Drug Administration, the agency charged with ensuring drug safety, 2007 brought a slew of charges undermining its credibility. The most widely reported involved a study by Cleveland Clinic cardiologist Steven Nissen showing that the diabetes drug Avandia, FDA-approved in 1999, raised the risk of heart attack by 30 to 40 percent. The agency was also called to testify before Congress about its inaction regarding side effects of the antibiotic Ketek and a widely used class of anemia drugs. In addition, a study published in the Archives of Internal Medicine in September found that reports of serious side effects and deaths caused by FDA-approved medicines nearly tripled between 1998 and 2005, to about 90,000.

The accumulation of evidence apparently forced a reckoning in Congress and the White House. On September 27, President Bush signed into law an amendment giving the agency unprecedented new powers to conduct and demand safety studies on approved drugs, police drug advertisements, and require companies to register data from their clinical trials in a publicly available database. The new law also boosts the agency’s budget, an increase approved in time to avert the layoffs of some 2,000 FDA employees, including many researchers.

“This has been a tough year,” acknowledges Janet Woodcock, deputy commissioner of the FDA and acting director of the agency’s Center for Drug Evaluation and Research. “[But] I do think this is an inflection point about the communication on drug safety. We have the opportunity to set up new systems.”

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Risky business

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(This Opinion column ran on Nature’s news site on August 21, 2007. You can download a pdf of the post.)

It’s not the technology of gene therapy but the regulation of clinical trials that we should be most afraid of, says Apoorva Mandavilli.

Almost exactly seven years after the first death in a gene-therapy trial, another unexpected death hit the field late last month – followed quickly by panic, outrage and some calls for an end to gene therapy altogether.

But to blame and ban all gene therapy because of this would be rash and misguided. And it might risk missing the point. What we should be most outraged and scared by is the way this trial took place — and the similar mis-steps that seem to accompany a vast number of clinical trials, gene therapy or no gene therapy.

On 2 July Jolee Mohr, a 36-year-old woman in Chicago, received an injection she thought would treat her painful — although not debilitating — arthritis. She died on 24 July of multiple organ failure, which was also the cause of death of 18-year-old Jesse Gelsinger in September 1999. In each case, the US Food and Drug Administration responded by suspending the trial and any others that used a similar approach.

But tragic and avoidable as both deaths were, I think we should be more worried about a broken system for clinical trials than of a risky treatment.

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Unreasonable doubt

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(This Opinion column ran on Nature’s website June 15, 2007. You can see the original post here.)

A ‘vaccine court’ case on autism could have disastrous consequences if people confuse its verdict with scientific consensus.

Why are there so many more cases of autism now than there were 30 years ago? It’s a question the best scientific minds have been unable to answer. But I’m afraid a US court now looking at that question may settle it on the basis of emotion rather than science.

The parents of thousands of autistic children think that the routine measles-mumps-rubella (MMR) vaccine and the mercury-based vaccine preservative called thimerosal damaged their healthy children’s brains and made them autistic — and they’re now suing the US government for damages. On Monday, three ‘special masters’ of the US Court of Federal Claims began hearing testimony in the first of nearly 5,000 such cases, some of which have been pending for years.

I sympathize with these parents and can understand their need to find a reason for their children’s suffering. But I trust in science, and I can’t ignore the fact that so many peer-reviewed studies — and every scientific panel entrusted with evaluating those studies — has come to the same conclusion: neither the MMR vaccine nor thimerosal is associated with autism.

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Don’t rush your vaccines

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(This Opinion column ran in Nature’s news site on May 17, 2007. You can read the original post here.)

The ethical debate about a vaccine for a sexually transmitted disease has been premature, says Apoorva Mandavilli; we don’t even know how well it works.

Here’s a good lesson: before you start pushing for a controversial vaccine to be made compulsory, best wait for the research — and I mean all the research — to come up with results.

For more than a year, we’ve been hearing that there is a vaccine that is 100% safe and effective in protecting young girls and women from the deadly viruses that cause cervical cancer.

Merck’s Gardasil, a vaccine against human papilloma virus (HPV), has been hailed as perhaps the biggest boon for women since the contraceptive pill. Across the world, including many American states, politicians and activists have proposed laws to make Gardasil mandatory for girls in their early teens or younger. Australia has already started a national programme of free vaccines for young girls.

All that sounds a bit premature — and rightly so. As we find out more about this vaccine, including new studies in last week’s New England Journal of Medicine¹^,², it’s clear we simply don’t know enough about it to be giving it to young girls en masse.

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No periods. Fullstop.

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(This post appeared on Nature Medicine’s Spoonful of Medicine blog on May 9, 2007.)

If you could take a pill that completely eliminates your periods, would you?

Women taking Seasonale have four periods a year.

Turns out the answer is rather emotional for many people. I say people because some men seem to have strong feelings about it too (as they do about many things that affect only women).

Most contraceptive pills entail 21 days of hormones, followed by 7 days of placebo. What follows is a period only in name, since women don’t actually ovulate while taking the pill. This fake period was designed into the pill when it was first introduced in 1960 so as not to freak women out too much.

This month, the FDA is evaluating Wyeth’s Lybrel, with which women would take hormones for a full year or longer (Women taking Seasonale, available now, still have 4 periods a year), remaining period-free throughout. And this is getting many experts riled up: those who think it might be unsafe, yes, but also those who argue that it is culturally dangerous–as in, it redefines femininity! Ahem.

Last year, I summarized the pros and cons of pills like Lybrel for the mainstream magazine Women’s Health, but briefly: the new pill could be healthier, because it cuts down on the hundreds of periods women now have on average as compared with about 50 or so not too long ago. On the other hand, we don’t really know what the long-term consequences might be.

So, what would you choose?

Science on trial

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(This post appeared on Nature Medicine’s Spoonful of Medicine blog on May 1, 2007.)

It’s always frightening when matters of science are settled in a court of law. And a relief

Robert Gallo

when reason prevails.

Last week, an Australian judge declared that yes, HIV does exist and that it causes AIDS.

The criminal case was filed against a HIV-positive man, Andre Chad Parenzee, for knowingly exposing his sexual partners to the virus. In his defense, he maintained that “the existence of HIV has not been proven” and that “there is no scientific evidence that AIDS is caused by a unique infectious agent.”

The case dragged on for months and although it wasn’t covered much outside the US, did create waves in Australia. Robert Gallo, who established the link between HIV and AIDS in 1984, appeared (by videolink) for the prosecution and was grilled by the defense about his research and his notorious squabble with French virologist Luc Montagnier. AIDS denialism has its supporters even among scientists and the dissident Perth Group, led by two Australian doctors, appeared as “expert witnesses” for the defense.

Parenzee had been convicted on three counts of endangering lives and had appealed. Justice John Sulan said last week that the Perth Group witnesses lacked credibility and threw out the appeal.

The two doctors continue to be employed by the Royal Perth Hospital, although AIDS Truth, a loosely banded group of scientists and activists, and other are calling for their dismissal. As I’ve written here before, AIDS denialism has serious consequences in some parts of the world and is not simply an academic debate. It’s time Australian scientists joined these activists in making sure science prevails.