The debate over the use of succinylcholine in children focused the anesthetic community’s interest on the interaction between the U.S. Food and Drug Administration (FDA) and ‘the drug companies’ that manufacture the pharmaceuticals we use daily. Innuendoes that the drug company involved had a vested interest in changing the label was one often heard comment on E-mail. While the debate was lively, there were some important general issues that were brought, to the attention of the anesthetic community and which have generic importance. As the Chairman of the FDA Advisory Committee for Anesthetic Drugs and Life Support, I offer the following observations.
The Advisory Committee of the FDA acts purely as a consultant to the FDA. It does not set policy. It is composed of anesthesiologists, nurse anesthetists, and members from both academic and private practice settings. The FDA also relies on outside consultants to serve on the committee when their expertise will be valuable. The Advisory Committee for Anesthetic Drugs and Life Support is somewhat unusual. It was one of the first of the advisory committees to use a rapid response method for the evaluation of new drugs.
In the past, drug manufacturers submitted products to the FDA for approval. A medical officer at the FDA reviewed the work, and after a lengthy period of time, a decision was made whether this drug should be released to the public. The change in the process was instituted in order to get a more rapid approval of drugs.
Propofol was the first drug approved through the new method. Instead of the bulk of the work being done by the medical officer of the FDA, members of the committee took specific areas and examined them in detail. All members of the committee were involved in writing of the package insert. It should be pointed out that an initial draft of the package insert is written by the drug company and modified by the FDA prior to final acceptance. The package insert is aimed at giving the practitioner as much information as possible in order to use the drug safely. It should be emphasized that drugs once approved by the FDA are available for use by all physicians and not for a group of specialists alone.
To re-examine the package insert for succinylcholine was a new experience for this Advisory Committee. The committee was dealing with a known drug that had been given millions of times but a new package insert was being requested. The proposed package insert change came about because of the reported cases of rhabdomyolysis that occurred in apparently healthy children. It was the feeling of the committee, on the initial review, that this was an important finding and that there were children who were dying from the use of this drug. No one knew the incidence of the problem, but it was assumed to be very low. However, it was also argued that these were preventable deaths. The committee debated for a period of time various ways to distribute this information to physicians who use the drug. The deliberations of the committee suggested that a boxed warning be placed in the package insert in order to alert all physicians to this new finding. After meeting with the Advisory Committee, the package insert that appeared contraindicated the use of the drug in children. While I have no special knowledge concerning what transpired after the meeting and before the package insert change, I offer the following insights. The drug company was taking the most conservative possible position in putting out this package insert with the contraindication. They knew there was a problem, though small, with their drug and the best way to protect the company was to insist on the contraindication classification.
Furor over the package insert was intense. Many groups and individuals started a campaign to change or eliminate the formal contraindication of succinylcholine in children. They pointed out many advantages of succinylcholine and argued the point convincingly. The FDA agreed that a more full discussion of the change was indicated. The FDA convened another meeting of the Advisory Committee and invited the anesthetic community to comment on the package insert. The committee reaffirmed its belief that this phenomenon was a problem and again recommended that a boxed warning be placed on the package. The precise warning to appear on the new package insert has not been finalized. However, an initial draft would suggest that the drug company will recommend against the routine use of succinylcholine in children.
The role of the Advisory Committee has served the FDA well. It has tried to bring practical concerns to the FDA at the same time that it considers the welfare of the population on which these drugs are used. Perhaps the succinylcholine debate did more to educate the anesthetic community about the dangers of hyperkalemia in a small subset of children than any other mechanism we presently have available to transmit this information. I also believe that it has given a new importance to the package insert in terms of education and use. One would have to commend the FDA for trying to make the package insert the distillation of all of the important information about a drug that we might administer to our patients.
We all work in our own specific settings and have little knowledge of the practices of others elsewhere. The FDA has a much more complete view of how we as physicians use drugs. Unfortunately, some physicians do not use drugs wisely and the FDA has tried to educate physicians through the package insert. Certainly, the succinylcholine controversy emphasizes that point.
Edward D. Miller, Jr., M.D. Professor and Chairman
Department of Anesthesiology and Critical Care Medicine
The Johns Hopkins Hospital, Baltimore, MD