Ritalin may alter brain, study shows
11/14/2004 7:18:58 PM

Changes appear similar to those caused by amphetamine.

The stimulant Ritalin, a drug used to help children with attention deficit hyperactivity disorder, may cause long-term changes in the brain, researchers reported on Sunday.

‘Children have been given Ritalin daily for many years ... but it’s not quite as simple as a short-acting drug.’
— JOAN BAIZER
Ritalin researcher         

The changes look similar to those seen with other stimulants such as amphetamine and cocaine, at least in rats, the team at the University of Buffalo found.  “Clinicians consider Ritalin to be short-acting,” Joan Baizer, a professor of physiology and biophysics who led the study said in a statement.  “When the active dose has worked its way through the system, they consider it ‘all gone.’ Our research with gene expression in an animal model suggests that it has the potential for causing long-lasting changes in brain cell structure and function.”

But Baizer said that Ritalin, known generically as methylphenidate, probably is not addictive in the way drugs of abuse are if it is used properly.  “Children have been given Ritalin daily for many years, and it is extremely effective and beneficial, but it’s not quite as simple as a short-acting drug,” she said. “We need to look at it more closely.”  

High doses of amphetamine and cocaine have been found to switch on genes known as “immediate early genes” in brain cells. One of the genes, called c-fos, has been linked with addiction when it is activated in certain parts of the brain.  The researchers gave rat pups sweetened milk carrying methylphenidate in comparable doses and at similar times to what a child would get.  C-fos genes were activated in their brains in a pattern similar to that seen in cocaine and amphetamine use, the researchers told a meeting of the Society for Neuroscience in San Diego.
      
“These data do suggest that there are effects of Ritalin on cell function that outlast the short term and we should sort that out,” Baizer said.  She said perhaps a gene chip — a microarray - could be used to see just which genes are turned on and off by methylphenidate.

Gates’ foundation buys drug shares
11/14/2004 7:24:11 PM

Investment in pharmaceutical companies totals nearly $205M

Poor countries have sometimes threatened to seize patents in order to produce affordable generic drugs for sick citizens, making the field of intellectual-property law a flash point between pharmaceutical companies and poor countries. At a meeting in Africa last year, Mr. Love says he was struck by fears of officials from Botswana and elsewhere that pressing for access to generic drugs could jeopardize their chances for contributions. “They thought it would alienate the Gates foundation and they thought that was a problem,” Mr. Love says. 

A report issued last year by the Commission on Macroeconomics and Health, chaired by economist Jeffrey Sachs, made a strong defense of intellectual-property protection as critical to continued investment in drug research and development. The Gates foundation was a major sponsor of the commission.

Other people involved with the issue say medical progress in poor countries depends on incentives for drug makers, and the Gates foundation is balancing the tradeoffs responsibly. “For every major killer of the poor, we need better drugs, better diagnostics and better vaccines,” says Richard Feachem, director of the Institute for Global Health at the University of California, San Francisco. “That means massive investments in research and development. Much of that has to come from Big Pharma and biotech companies.”

The foundation’s Mr. Cerrell dismisses as “speculative” the suggestion of conflict between financing drugs and investing in stocks. He adds that pharmaceutical makers “play an important part in meeting our goals of providing equity and access and lifesaving vaccines and other advances in medicine to those who need it most.”

Managing the foundation’s multiplying ties with the drug industry could get tricky. For example, through its funding for the Global Alliance for Vaccines and Immunizations, the foundation pays for purchases of vaccines from some of the same pharmaceutical makers in which it now owns shares.  
 
A Gates foundation representative sits on the 18-member board of the Global Fund to Fight AIDS, Tuberculosis and Malaria, which is expected to become a major buyer of drugs to fight those diseases. The foundation has pledged $100 million to the fund, which has so far collected $2.2 billion.

UC’s Mr. Feachem, recently appointed to head the Geneva-based fund, argues that its massive buying power could create a strong “pull factor” spurring drug makers to develop inexpensive products. “For the industry, that would lead to the development of a high-volume, low-margin market, which could be a win for them as well,” he says.

Mr. Gates has forged other ties with the industry. Last year, Microsoft named Raymond Gilmartin, chief executive of Merck, to its board. Mr. Gates worked with Mr. Gilmartin to launch the vaccine fund and also helped Merck with a program to supply discounted AIDS drugs in Botswana, where one in three people is infected with HIV.

The foundation’s stock holdings include just two other stocks: Cox Communications Inc. and Waste Management Inc. The spokesman for Mr. Larson, the money manager, confirms that the drug investments represent a significant increase in the foundation’s equity holdings, though they represent less than 1% of its total portfolio.

Study faults industry clinical trials
11/14/2004 7:28:45 PM

Company-backed tests rarely follow guidelines, report finds

The drug companies that pay for major testing of most new medicines give the participating university researchers little or no say in how the studies are designed and how the findings are handled, a survey found.
      
Pharmaceutical companies have sponsored research that found a drug didn’t work or was dangerous, then suppressed the results.

The survey of 108 medical schools, published in this week’s New England Journal of Medicine, is the latest sign of growing concern about conflicts of interest between those doing scientific research and the pharmaceutical companies sponsoring it.

“What the institutions have told us is they feel almost powerless in these contracts,” said Dr. Kevin Schulman, a Duke University Medical Center professor who led the survey.  While federal agencies sponsor much early research, large-scale studies of drugs’ safety and effectiveness are usually paid for by the manufacturers. Typically, the companies hire medical school faculty members to carry out the studies.
      
ISSUE: LACK OF CONTROL
But some scientists worry their lack of control could threaten the integrity of research and the safety of the volunteers participating. Among other things, pharmaceutical companies have sponsored research that found a drug didn’t work or was dangerous, then suppressed the results.  
 
Concerned about the problem, the International Committee of Medical Journal Editors in 2001 published guidelines for research contracts between medical schools and the pharmaceutical industry.

Last winter, researchers at Duke University Medical Center and Duke’s law school interviewed officials at U.S. medical schools and reviewed some of their research contracts to determine how many complied with the new guidelines. Only a minority did.  Schulman said researchers have less and less control over patient trials as more and more studies include dozens of medical centers, rather than just one, a strategy meant to bring results faster.
      
FROM THE REPORT
Among the study’s findings:
Researchers rarely were allowed a say in the design of the clinical trials, with only 10 percent of contracts covering how data is collected and monitored and only 5 percent covering how data is analyzed and interpreted.

Less than 1 percent of contracts guaranteed that results would be published and that an independent committee would have control over that. But 40 percent of contracts addressed editorial control of manuscripts.  Only 1 percent of contracts required an independent board to monitor patient safety. Such boards can stop a study early if the treatment is found to be harming participants.

“It is very worrying,” said Mary Ann Baily, associate for ethics and health policy at the Hastings Center, a Garrison, N.Y., think tank. “The future of research and patient welfare does depend on how we approach this.”

Financial ties between academic researchers and industry sponsors already are under scrutiny for apparent conflicts of interest, as when researchers receive stock in a company testing an experimental drug.
      
Over the summer, the Pharmaceutical Research and Manufacturers of America established voluntary guidelines for clinical research, but they are “basically toothless,” said Dr. Jeffrey M. Drazen, editor of the New England Journal.

“The system would be better served if there were universally accepted contractual language,” he wrote in an editorial.  PhRMA spokesman Jeff Trewhitt said its member companies three weeks ago started implementing new principles for operating and reporting on clinical trials that “reaffirm our commitment to the safety of research participants and a timely communication of research results.”

Trewhitt said those principles cover at least some of the concerns raised in the study and recommend paying researchers in cash, not company stock.  In another opinion piece, doctors wrote that such protections are critical because future medical research will depend even more closely on partnerships between universities and industry; they suggested creating a national panel to deal with conflict-of-interest issues.  A third opinion piece by doctors and an industry consultant said universities must set firm policies protecting their researchers from financial influences.