Scientific panel concludes AIDS study that violated fed rules still OK

Thursday, April 7th 2005, 1:17 pm

By: News On 6

WASHINGTON (AP) _ Controversial U.S. research in Africa that violated federal patient protection rules was nevertheless conducted well enough to support its conclusions that the AIDS drug nevirapine could be used safely to protect babies from the disease, an expert scientific panel has concluded.

``The committee finds that there is no reason based in ethical concerns about the design or implementation of the study that would justify excluding its findings from use in scientific and policy deliberations,'' the Institute of Medicine panel said in a report first obtained by The Associated Press.

The report, which was released Thursday, will have implications in both Africa, where medical officials are debating whether to withdraw the drug, and in the United States, where investigators are examining whether U.S. research is complying with federal law.

The report will be welcomed as good news at the National Institutes of Health, the federal agency that funded the nevirapine study in Uganda and which has been engulfed in months of controversy but has insisted the drug is safe.

The Elizabeth Glaser Pediatric AIDS Foundation, one of the largest providers of AIDS assistance in the Third World, hailed the report's finding, saying those who have and are taking the drug in single doses can now be sure it is safe.

``I think this will now allow us to put to rest the questions about the safety and efficacy of nevirapine,'' said Mark Isaac, the foundation's vice president. ``Our sense is we now can focus on the real issue saving lives.''

AP reported in December that U.S. Office of Human Research Protections had concluded the NIH experiment in Uganda that dated to the mid-1990s had violated federal patient safety rules.

However, NIH did not inform the Bush White House of the problems before the United States began sending hundreds of millions of dollars of nevirapine to Africa in 2002 to try to stop the spread of AIDS from infected mothers to their babies.

NIH acknowledges its study suffered from flawed document keeping and violated some federal regulations, but that it believed its scientific conclusions about nevirapine's usefulness and safety remained valid. It requested the IOM study.

The IOM report states that it, too, found ``procedural lapses,'' record-keeping problems, some unreported adverse events and instances in which researchers failed to get consent to keep African children in the experiment for longer than intended in instances where their mother may have died.

The panel said the underreporting of some bad reactions, known as adverse events in the scientific world, ``may limit the generalizability'' of some of the study's conclusions.

But it added, ``while there were some procedural deficiencies reported by auditors, none appeared to have affected the outcome of the study'' and that no patients in the experiment were ever put at serious jeopardy.

The document is unlikely to end congressional and federal investigations into whether the NIH safety and legal compliance officials' repeated concerns about this and other research projects were repeatedly disregarded by managers and front-line researchers.

AP reported last month that six of the nine experts that served on the panel currently get money from NIH, the agency whose conduct they were reviewing. Some member of Congress have questioned whether the financial ties should weaken the report's credibility.

And the IOM panel did not address new emerging data showing nevirapine can create resistance that lasts for months in women or children who took even a single dose, rendering some treatments for their AIDS less effective.

That concern has caused South Africa to call for the end of nevirapine's use to prevent mother-to-baby transmission of AIDS. More expensive cocktail combinations of drugs are likely to be used.

Isaac acknowledged the resistance issue was a concern and that nevirapine should be used to protect babies only when other, better cocktail treatments aren't available. ``This report makes clear nevirapine is part of our arsenal, but it is only part of the arsenal,'' he said.

The study also steered clear of the controversy of whether the NIH study complied with Good Clinical Practices (GCP), a sweeping set of record-keeping and patient protections that NIH says it is requiring its researchers to follow.

The IOM panel said GCP was voluntary and that it remained confident the researchers for the study were in ``substantial compliance'' with the federal guidelines they were obligated to follow _ some of which were tougher than the GCP conditions.

Meanwhile, federal and congressional investigations into disputes between NIH's researchers and the agency officers charged with safety and compliance have elicited new information showing that some concerns reached high into the agency.

For instance, the No. 2 official in the AIDS division, Dr. Jonathan Kagan, wrote an e-mail rebuking his boss, AIDS division director Dr. Edmund Tramont, for trying to give an award to the front line researchers in the Uganda study within months of the problems surfacing.

``We cannot lose sight of the fact that they screwed up big time,'' Kagan wrote Tramont in the 2003 e-mail provided to AP. ``And you bailed their asses out. I'm all for forgiveness, etc. I'm not for punishing them. But it would be 'over the top' to me to be proclaiming them as heroes.''