Ribavirin and Mortality: New Information

This reporter obtained previously-unpublished information comparing persons with ARC who chose to use or not use ribavirin after finishing major clinical trials conducted at four medical centers in 1987. The numbers look very good, but they are not conclusive because of the way self-selection worked in this case.
After the patients completed a double-blind placebo study of ribavirin, they were entitled to obtain the drug free if they wanted it, in return for their participation in the study. A total of 116 patients (from both the ribavirin and placebo groups) did choose to use the drug in this "open-label" phase of the study; 74 chose not to. In the 116 who did use ribavirin there were 6 deaths (5 percent), but in the 74 who did not use ribavirin there were 25 deaths, or 34 percent.
Some of these patients had been on ribavirin for as long as 80 weeks; others, in the placebo group in the original study, had been using the drug for less time.
These figures look conclusive, but they could have happened by self selection. Suppose ribavirin didn't do anything. The patients who happened to be doing well while on ribavirin in the study would be likely to want to stay on the drug, since it would have seemed to be working for them. But those patients who happened to be doing poorly would be likely to drop the drug in order to switch to AZT, which cannot be combined with ribavirin. The result is that those who were doing well would tend to put themselves into the ribavirin group, while those doing poorly would go into the other group. This self selection of healthier patients into the ribavirin group during the open-label phase of the study could have caused a difference in death rates, even without any effect from the drug.
It may be possible to analyze the patient records to see how much of the difference in death rate could be attributed to self selection and how much to the drug. This analysis will almost certainly require subjective judgments. And ribavirin has become so politicized that it will be hard to trust this judgment to any researchers not truly independent of both the drug's manufacturer and the FDA. We don't know how such a study could be arranged.
In the absence of better information, it seems unlikely to us that this large difference in death rate could be explained solely by self selection--especially since all patients entering the trial had to meet medical inclusion criteria designed to give a fairly homogeneous group for the study. Instead, this information seems to fit with anecdotal reports that some persons have stopped using ribavirin and quickly deteriorated, whereas others stopped it and had no change. It is possible that ribavirin delays certain stages of progression of HIV infection, while having little or no effect at other stages. It may be possible to study this question by using newer diagnostic tools, such as the P-24 antigen test.

Ribavirin Update

On January 15 we published a short article, "Ribavirin Available By Prescription?". We have since heard from Roberts S. Smith, a director of ICN Pharmaceuticals (the manufacturer of ribavirin), and of Viratek (the ICN subsidiary which developed the drug). He asked us to make it clear that ICN had nothing to do with the plans described in the article, and that to the best of his knowledge their product was not being used.

Ribavirin By Prescription?

Ribavirin has been available in the U.S. by prescription for some time, but the only FDA-approved use has been for aerosol treatment of respiratory syncytial virus in infants. Physicians are, however, allowed to use an approved drug for other than approved uses. (An excellent discussion of this issue appeared in the FDA Drug Bulletin Volume 12 Number 1, April 1982. It points out that gaining FDA approval for legitimate medical advances "may take time and, without the initiative of the drug manufacturer whose product is involved, may never occur. For that reason, accepted medical practice often includes drug use that is not reflected in approved drug labeling." (You can get the FDA Drug Bulletin from a Federal depository library--which can be found in most cities.)
Recently we heard from a pharmacist that he could fill prescriptions for ribavirin if the physician specified that it be used "as directed". This would be the official ribavirin, not an imitation product.
However we have not heard from anyone who has actually obtained and used the drug in this way. And according to Martin Delaney of Project Inform, ribavirin is sold only through hospitals, since the aerosol treatment for infants is not suitable for home use.
If a pharmacy does have the drug, we suspect that the words "as directed" get the pharmacist off the hook, leaving the issue of prescribing ribavirin for treatment of AIDS or ARC between the physician and the FDA. And physicians as a group have long been protective of their right to practice medicine as they see fit; they have considerable political power when they use it, and when the laws were written they were careful to guard their professional sphere against intrusions. Pharmacists in this country do not have the same protections. The phrase "as directed" apparently works its magic by not giving notice to the pharmacist of the non-approved use.
Ribavirin is of course a special case, in that a state of war has developed between ICN, the manufacturer, and the FDA. ICN has not always played by the rules--rules of a game which has grown to be rigged against small to medium companies like ICN, in favor of giants like Burroughs-Wellcome. We don't know who will win this war, but tragically we do know who will lose it. No one knows for sure whether ribavirin does any good for persons with ARC or AIDS, but few could have confidence in the system currently in place for finding out.
We should add that ICN had nothing to do with our comments here, and knew nothing about them in advance. While physicians are allowed to prescribe approved drugs for non-approved uses, drug manufacturers are strictly forbidden to do anything to encourage them to do so.
And physicians have been reluctant to exercise or even discuss the rights they have--possibly from fear of losing professional flexibility if the issue came to a head. Physicians have already lost influence and freedom in the face of Federal efforts to control medical costs. The big money in medicine, which so enriched U.S. allopathic physicians by legislating rival systems out of existence earlier in the twentieth century, may turn against its beneficiaries now that bigger money is involved.

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