Author Archives: Amy Maxmen

US agency hopes to curb prescription painkiller abuse with education

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Today the US government has begun to make good on a promise to curb the nation’s epidemic of prescription-painkiller abuse.

The US Food and Drug Administration (FDA) announced that doctors and patients will have access to training and educational materials on the risks of abuse and addiction associated with opioids, a class of medications prescribed for severe pain.

In the United States, opioids such as Oxycontin are abused both by patients for whom they’re prescribed and recreational users. They accounted for 14,800 deaths by overdose in 2008 and 15,597 deaths in 2009, according to the Centers for Disease Control and Prevention. Last year, more people died from prescription-opioid overdoses than from heroine and cocaine overdoses combined.

“Prescription-drug abuse is our nation’s fastest-growing drug problem,” said FDA commissioner Margaret Hamburg at a press briefing on the measure. “Today, the FDA is taking the next critical step in risk management.”

The FDA is requiring companies that manufacture long-lasting or extended release opioids to pay for educational materials that teach doctors how to communicate the risk of opioid dependence to patients and how to handle those who’ve become addicted. Between now and March 2013, some 20 companies will develop educational strategies, which must adhere to a blueprint issued by the FDA. A third party will audit the materials to ensure that they are comprehensive and free from bias.

This risk-management plan has been two years in the making. It was included as a proposal in the Administration’s 2011 Prescription Drug Abuse Prevention Plan.

One clear shortcoming of the approach is that opioid prescribers can skip training sessions, and patients might not read pamphlets that health-care providers give them. In other words, it’s mandatory for companies to provide education, but not for people to listen. Hamburg says that the agency expects 60% of the current 320,000 prescribers to attend the training sessions by 2016. “We’d like to see a higher number,” she adds, “and we are working with Congress to explore a way of mandating training.”

Before that happens, the FDA must demonstrate that the training would not add additional burdens to busy healthcare providers, or restrict opioid access to deserving patients. Surveys conducted once the plan is in place should shed light on both of these concerns, Hamburg says.

Researchers highlight the impact of slavery on health and disease

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Scientists who study health disparities gathered today and last week to discuss the well-being of descendants of the slave trade.

Usually, researchers describe the health of different races and ethnicities regardless of their past. For example, infants born to black women are 1.5–3 times more likely to die than infants born to white women. Forty-two per cent of African Americans have been diagnosed with hypertension, compared with 28.8% of white people. And for all cancer types combined, the death rate in the United States is 25% higher for black people than white people.

Biological, environmental and socio-economic factors create the disparities. And Thomas LaVeist, the chairman of the International Conference on Health in the African Diaspora (ICHAD), which was held in Baltimore, Maryland, on 5–8 July, argues that the history of slavery and subjugation of a subset of black people also plays into health.

“My career has been about understanding the factors that produce health disparities, and I don’t know how you would engage that question without looking at the levels of second- and third-class citizenship that Africans have endured,” says LaVeist, who is also director of the Hopkins Center for Health Disparities at Johns Hopkins University in Baltimore, Maryland.

“We’re talking about a period that fundamentally redesigned the planet by moving a massive number of people from one side of the world to the other,” he explains. “After the slave trade ended, slavery continued until 1888, when Brazil was the last country to abolish it. And then there was a period of segregation and second-class citizenship up until the 1960s.”

On 8 July the ICHAD working group released a draft declaration for comment, to be finalized by late summer. Among other statements, this version states that the approximately 160 million descendants of the transatlantic slave system living in the Western Hemisphere tend to experience poor living conditions, higher levels of morbidity and less access to health care, and that the analysis of rigorously collected data should be used to define appropriate solutions for improving the health of this community.

Rather than compare data collected in nation-wide surveys, researchers should design studies that minimize confounding factors, says LaVeist. Such studies might compare health indicators, such as infant mortality rate, across different populations who are of the same class and inhabit the same neighborhood.

The studies presented at ICHAD reflected a comparative approach. For example, Pedro Ordunez-Garcia, of the Pan American Health Organization based in Washington DC, concluded that the narrow gap in hypertension prevalence between blacks and whites living in Cuba — as compared to the United States — reflects the importance of medical attention. Most people receive tests and treatment for hypertension in Cuba, a country renowned for its socialized health care, says Ordunez-Garcia.

Speakers also tended to emphasize socio-economic, environmental and dietary conditions rather than biological factors. Indeed, LaVeist calls the current attention to genetics in disease research overblown.

Although he admitted that the bulk of health disparities are socially determined, Rick Kittles, a geneticist at the University of Illinois College of Medicine at Chicago, urged his mainly black audience at ICHAD to not distance themselves from genetics research. In some diseases, such as breast and prostate cancer, genes may have an important role. Moreover, he added that doctors will increasingly use genetic tests to predict how patients respond to medicines. If those tests aren’t developed to assess the DNA of black people, he warns that this already underserved population might not benefit from advances in personalized medicine. “You might not like genetics,” he said, “but we need to be at the table.”

Widespread praise for US drug bill

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As the House of Representatives voted to approve legislation that helps move drugs through the pipeline this afternoon, Margaret Hamburg, the commissioner of the US Food and Drug Administration (FDA) praised the bill’s revised approach to risk management.

Hamburg sat on a panel with leaders in biotechnology and patient advocacy at the 2012 BIO International Convention this week in Boston, Massachusetts. Prompted by questions from the moderator, the five panelists discussed the revision of the Prescription Drug User Fee Act (PDUFA), which reauthorizes the FDA’s programme to grant companies faster drug and medical-device approval in exchange for money.

The bill, PDUFA V, has received widespread support in Congress thus far. As long as the Senate approves the version that the House voted on today, President Obama will sign it into law.

What follows is an edited version of the panel’s discussion, moderated by Steve Usdin, editor at BioCentury, at BIO today. Continue reading →

Biotech report says IP spurs innovation

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Some people say that patents on intellectual property (IP) stifle progress when they occur at early phases of research. However, history suggests the opposite, according to a report presented at the 2012 BIO International Convention in Boston, Massachusetts.

“There’s been active debate about whether stronger intellectual-property rights are a help or a hindrance to developing industries,” says Joseph Damond, vice-president for international affairs at the Biotechnology Industry Organization (BIO), which commissioned the report to add evidence to the argument.

Questions about IP’s impact on research are particularly crucial to countries that are beginning to invest in biotechnology.  So that they could advise those countries on IP regulations, BIO asked for an assessment of IP trends in nations around the world. In response to their request, Pugatch Consilium, a consultancy group based in Israel and the United Kingdom, combed through publications and databases for associations between IP rights (IPR) and measures of economic development and biotech health.

“In the literature we found that no, patenting does not stand in the way of research,” says David Torstensson, a senior consultant at Pugatch and an author on the report presented 19 June. At the talk, which was comprised of biotech fans, the audience appeared to agree with his pro-IP conclusion.  Continue reading →

Gene patent case ramps up

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Today the American Civil Liberties Union (ACLU) and others file legal documents challenging patents on DNA.

The ACLU briefs detail their case against seven patents held by Myriad Genetics, a diagnostics company based in Salt Lake City, Utah, regarding two genes associated with a high risk of breast and ovarian cancer, BRCA1 and BRCA2.

On 20 July, the ACLU and the Public Patent Foundation will argue the case in front of a judge at the federal appeals court in Washington DC, on behalf of patients, investigators and doctors.

It’s a flashback to 2011, when Myriad won this battle. The case was revived in March when the supreme court ruled that patents on a blood test from the California-based diagnostics company Prometheus Laboratories were invalid because they simply reflected ‘a law of nature’. Specifically, the test measures components in a person’s blood to determine correct drug dosing.

The ruling against Prometheus’s patents “reinvigorated our concern that there are too many patents on natural phenomenon”, says Sandra Park, an ACLU attorney representing the plaintiffs. “That’s what we’ve been arguing all along, but now that the court has reiterated it, we are arguing that this supreme court doctrine that prohibits the patenting of laws and products of nature needs to be taken more seriously.”

The debate centres on whether DNA extracted and amplified from patients is a product of nature. The ACLU says that it is, but Myriad argues that isolated DNA is structurally and functionally different than DNA within a person, and therefore patentable because it is no longer a product of nature.

In its briefs, the ACLU also fights against Myriad’s patents over certain methods. Specifically, the company put a patent on their protocol to predict how patients with BRCA mutations will react to cancer drugs. In it, they compare how cells with and without the BRCA mutations grow in response treatments. The patent claim means that Myriad can stop investigators from using that method in their research. Park says that patent should also be invalid because it “monopolizes a law of nature”.

This case packs a punch because several companies own genes, and many more plan to do the same. Biotech companies argue that if DNA cannot be patented, there is little incentive to invest money in developing genetic tests. On the other side, investigators and patients argue that the patents ultimately stifle research and limit patients’ testing options.

Advertising masked as science?

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A former employee of a pharmaceutical company blows the whistle on drug promotion disguised as science in an editorial published today.

Drug companies occasionally conduct post-marketing studies to collect data on the safety and efficacy of drugs in the real world, after the drugs have been approved by the US Food and Drug Administration (FDA). “However,” writes the anonymous author in the British Medical Journal, “some of the [post-marketing] studies I worked on were not designed to determine the overall risk:benefit balance of the drug in the general population. They were designed to support and disseminate a marketing message.”

Promotion enters into the picture as the company recruits doctors to enrol their patients into the study – a job for which they’re paid. The company tells doctors about the qualities of their drug, and the doctor relays that information to their patients.

According to the whistle-blower, the results of these studies were often dubious. “We occasionally resorted to ‘playing’ with the data that had originally failed to show the expected result,” he says. “This was done by altering the statistical method until any statistical significance was found.” He adds that the company sometimes omitted negative results and played down harmful side effects. After all, post-marketing studies don’t face the scrutiny that pre-approval studies do.

Why would a company resort to devious methods? After spending millions of dollars to develop a drug, companies scramble to recoup their investments in the decade that a patent lasts, writes the author. Continue reading →

Brains thaw at Harvard repository

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It’s a scientist’s nightmare come true. Molecular information stored within 147 brains was lost when a freezer failed at Harvard’s brain bank at McLean Hospital in Belmont, Massachusetts. Two alarm systems monitored the freezer’s temperature, but clearly, that wasn’t enough.

Most devastating is the fact that one-third of the brains derived from deceased people with autism. Donors are in short supply, and therefore autism researchers who rely on brain tissue for insight into the neurological disease consider these brains precious. Although the DNA within the samples probably remains intact, RNA and proteins were destroyed as the temperature warmed from −80° Celsius to 7° Celsius over three to four days in late May, according to a spokesperson at the centre.

“It’s a tragedy for the families who donated the brains, and it must be heartbreaking for the researchers to have lost this tissue,” says Ron Zielke, director of the National Institute of Child Health and Human Development (NICHD) Brain and Tissue Bank for Developmental Disorders at the University of Maryland in Baltimore. This and the Harvard centre at McLean are the only repositories in the United States that distribute autism brain tissue to researchers around the world. “Only about five to six brains become available per year, so when you lose a significant number like this, that means years worth of donations,” Zielke says.

Human mistakes and technological errors caused the disaster. Normally, to mitigate any risk of freezer malfunction, the employees disperse the autism samples between 24 freezers, says Francine Benes, director of Harvard’s centre. However, in April, almost one-third of the autism collection was consolidated into a single freezer in preparation for a visit from the Autism Tissue Program, which distributes brain samples to investigators who request it. Staff from the programme completed their work on 1 May, but the staff kept the brains consolidated because they were busy. “We were barraged with requests for samples, and the tissues seemed to be safe in that freezer, so we kept them there,” explains Benes. “Twice a day, our staff look at the electronic panel outside of the freezer that tells you its temperature and status, and it read, OK.” Continue reading →

Vitamin D fails diabetes test

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Vitamin D enthusiasts may be disappointed by the results of a clinical trial reported today at the American Diabetes Association meeting in Philadelphia, Pennsylvania. Huge supplemental doses of vitamin D did to not curb type 2 diabetes in people at high risk of the disease.

Vitamin D — a nutrient derived naturally from exposure to sunlight and, to a lesser extent, from certain foods — is the latest rage in the vitamin world. In the United States, sales of vitamin D supplements rose tenfold between 2001 and 2009.

Some doctors and nutritionists recommend that people take high-dose supplements to avoid diabetes, despite the fact that a panel convened by the US Institute of Medicine (IOM) found the evidence lacking in support of a role for the vitamin in non-skeletal health.

To put an end to the debate, Mayer Davidson, a diabetes researcher at Charles R. Drew University in Los Angeles, California, and lead investigator on the trial, gave people at risk of diabetes a placebo or an enormous dose of vitamin D3. In the past, vitamin D advocates have brushed aside studies with negative results by saying that investigators offered too low a dose. “I wanted to do a once-and-for-all trial,” Davidson says.

An ultimate answer?

Once a week for a year, participants in the treatment arm of the study took an average of 88,865 international units (IU) of vitamin D3, so that their circulating blood levels were 70 nanograms per millilitre. That dose is 21 times what the IOM recommended in their 2010 guidelines and three times what they said was safe. But Davidson says he saw no sign of harm, including kidney stones, which have occurred infrequently in other high-dose trials.

Rather than wait for healthy people to acquire type 2 diabetes, Davidson enrolled only those at high risk of the disease. The participants all were either Latinos or African Americans diagnosed with ‘pre-diabetes’ because their blood glucose levels were higher than normal.

Without drugs or behavioural interventions, roughly 10% of people with ‘pre-diabetes’ become diabetic per year, Davidson says. By the time his year-long trial ended, 9% of the participants in the placebo group had acquired the disease, compared to 12% of those in the treatment group. Statistically speaking, that difference was probably due to chance. “What we saw was that vitamin D did not change the natural history of the disease,” Davidson says, adding, “I think vitamin D’s a dead end for diabetes.” Continue reading →

Vital prescription-drug bill plods though Senate

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Lawmakers generally support the reauthorization of a piece of legislation that brings drugs to market at a reasonable pace.

But as the Senate meets this week to vote on their iteration of the Prescription Drug User Fee Act (PDUFA), the discussion slows as they wade though 17 amendments to the act proposed by Congress.

The PDUFA grants pharmaceutical, medical-device and biotech companies a relatively speedy review process for their products, in return for user fees to the US Food and Drug Administration (FDA). The agreement has cut review times in half, but the deal expires in September this year. If reauthorized, the act would generate about US$720 million in the 2013 fiscal year, according to the Congressional Budget Office. Without these funds, the FDA would need to lay off as many as 4,000 employees, said Senator Mike Enzi (Republican–Wyoming) at the proceedings today. “The pipeline for drugs would come to a grinding halt.”

Senate majority leader Harry Reid (Democrat–Nevada) has repeatedly begged Congress to pass the legislation swiftly, so that patients can get the lifesaving drugs they need.

If the Senate passes their version of the PDUFA, along with any adopted amendments, the bill would be combined with a similar one from the House of Representatives. The Senate and House would then vote on the amalgamated act, and if they approve it, President Obama would then sign it into law.

The amendments presented to the Senate pertain to hydrocodone, genetically engineered salmon sunscreen testing and more. One amendment sure to cause conflict between industry and consumer-protection lobbyists (if adopted this week) focuses on pharmaceutical fraud. Amendment ‘Sanders #2109’, from Senator Bernie Sanders (Independent–Vermont), calls for a stricter penalty on companies that illegally market a medication or inflate a drug’s price in bills to Medicare or Medicaid. If convicted of these crimes, a company would lose its exclusive rights over the drug.

“This would send a strong and clear message to the drug industry,” said Sanders in his Senate address today. “Illegal behaviour would not be rewarded with continued government-granted monopolies,” he said. Companies now face fines when convicted of illegal marketing, but Sanders argues that the penalties don’t deter companies from risky behaviour. “Every major company has either been found guilty of, or settled charges of significant fraud over the last ten years,” he says. “Is fraud the business model of the pharmaceutical industry?”

It may well be part of the model. Since 2010, the pharmaceutical industry has paid more fines for fraud than any other sector, surpassing defence contractors. Last year, that totaled $1.8 billion, and it’s projected to amount to $8 billion–9 billion this year, said Sanders. Fines may seem hefty, but they pale in comparison to annual profits, he said. Indeed, the top 12 pharmaceutical companies earned a total of $44.6 billion back in 2010.

Some major consumer organizations endorse the Sanders amendment. “The amendment provides a deterrent to prevent pharmaceutical companies from engaging in fraudulent activities in the first place,” says Sammy Almashat, a health researcher at Public Citizen, a non-profit in Washington DC that published a 2010 report on pharmaceutical industry fraud and supports the amendment. “Given the fact that this activity is profitable, the bad actors have a way of forcing good actors to follow suit, so this would level the playing field,” he says.

Almashat stresses that the amendment would not punish companies when a rogue employee runs a misleading ad, for example, and that it would not apply to companies found guilty long after their drug has been pulled from the market — as in the case of the painkiller Vioxx.

The amendment would have hurt the pharmaceutical giant Eli Lilly, had it been enforced in 2009 when the company pleaded guilty for promoting the antipsychotic drug Zyprexa as a treatment for dementia, even though the FDA had not verified that Zyprexa was safe and effective for these patients. Despite $1.4 billion in criminal and civil fines, Eli Lilly continued to benefit from nearly three more years of Zyprexa exclusivity. Between 2009 and 2011, Almashat says Zyprexa sales totalled $6.1 billion.

Update 24 May

At 3pm, the Senate voted against approval for the Sanders amendment. Earlier in the day, Jon Kyl (R-Arizona) called the amendment unnecessary, and said it would disincentivize innovation because companies would no longer have the financial security that exclusivity offers after they pay millions to bring a drug through the pipeline. Enzi echoed his sentiments, and added that in the case of fraud, the amendment “discourages any settlement agreements, people would fight to the death if they knew they would lose their exclusivity.” He concluded, “We need to combat healthcare fraud, but this amendment goes too far.”

Twenty minutes later, the Senate voted 96 to 1 in favor of reauthorizing PDUFA. Sanders was the 1 ‘nay’.

 

 

 

Anthrax vaccine trial meets bioethicists

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An anthrax vaccine would protect civilians from the long-term effects of a bioterrorist attack. But there’s no telling how children would react to the shots.

To assess the ethics of a trial, in which kids would get an anthrax vaccine unlikely to ever be necessary, a federal committee met today in Washington DC.

“The chance that we would have a widespread outbreak of anthrax are relatively low, but if anthrax were weaponized, it would be catastrophic,” explains Larry Gostin, of the O’Neill Institute Center on Public Health Law and Human Rights in Washington DC. “From a public-health perspective, it’s right to think about the best way to prevent these hazards.”

The Presidential Commission for the Study of Bioethical Issues is expected to finalize their decision by early next year. Their task follows a vote in favour of a paediatric anthrax vaccine trial by the US National Biodefense Science Board in October, who in turn had been asked for an opinion by the US Department of Health and Human Services (HHS).

Momentum for a trial began after the worrisome results of a doomsday “exercise” designed to test how the country would react to an immense release of anthrax spores in San Francisco. The project, called Dark Zephyr, found that 7.6 million people — including 1.7 million individuals under age 18 — would need to be vaccinated.

Regardless of a clinical trial, teens and children would immunized if disaster struck because the shots have proven safe in some 1.2 million vaccinated adults in the military, says Major General John Parker, the chair of the National Biodefense Science Board. Among other things, a trial would let clinicians know how much vaccine to give, he says.

Children complicate clinical trials, ethically speaking, because participants ought to fully grasp the risks and purposes of a trial before enrolling, and kids often do not. Other concerns voiced at the meeting included the fact that a paediatric anthrax vaccine trial is unlikely yield direct benefits to participants because there’s little chance of an anthrax attack, and an even smaller chance of an attack near the locale where the trial ensued.

Amy Gutmann, the chair of the bioethical issues commission, says that a strong case for the study would be made  “if the community that’s most supportive of moving this forward would volunteer their own children for the study”. Parker responded to the comment: “There are people in our population [the armed forces] that would like their family immunized.”

Some experts weren’t swayed by the putative pay-off of a trial. Nicola Klein, co-director at the Kaiser Permanente Vaccine Study Center, says that she’s not convinced that anthrax is now a credible threat. And Robert “Skip” Nelson, a paediatric ethicist at the US Food and Drug Administration, questions the need for a pre-emptive trial as opposed to one after a catastrophe hits. After all, people would take 60 days of antibiotics to ward off the immediate effects of an anthrax attack, whereas the vaccine would provide protection for future exposures. “If the argument is that a pre-event study is better,” he says, “I need to know the science behind why that is.”

HHS Secretary Kathleen Sebelius illustrated the gravity of the dilemma by voicing her appreciation for the bioethics commission and the experts at the meeting. “Your work is critically important to the 300 million people or so who are not in the room today,” she says. “And I thank you on their behalf because your work affects their lives whether they know it or not.”