New rules for industry-sponsored articles
Twelve prominent medical journals have joined forces to ensure that clinical trial information published in the peer-reviewed journals has not been influenced by drug- company sponsors.
Data published in these articles are assumed to be gathered and presented in an objective and dispassionate manner, says a joint editorial to be published by all of the journals. Discourse about the data shapes treatment decisions made by physicians and drives public and private health care policy.
In the current intellectual environment, however, drug companies may use the publication of trial information in the journals to market drugs and medical devices for their companies’ financial gain, the editorial states. This is in contrast to patients who may participate in the trials to advance the standard of care. "In the light of that truth," the editorial says, "the use of clinical trials primarily for marketing, in our view, makes a mockery of clinical investigation and is a misuse of a powerful tool."
The editorial’s authors denounce contractual agreements that deny investigators the right to examine the data independently or to submit a manuscript for publication without first obtaining the consent of the trial’s sponsor. The journals now will routinely require authors to disclose details of their own and the sponsor’s role in the study. Many of the journals will ask the responsible author to sign a statement indicating that he or she accepts full responsibility for the conduct of the trial, had access to the data, and controlled the decision to publish. The journals will not review or publish articles based on studies that are conducted under conditions that allow the sponsor to have sole control of the data or to withhold publication.
The joint editorial is signed by editors of the Annals of Internal Medicine, the Journal of the American Medical Association, the New England Journal of Medicine, the Canadian Medical Association Journal, the Journal of the Danish Medical Association, The Lancet, MEDLINE/Index Medicus, the New Zealand Medical Journal, the Journal of the Norwegian Medical Association, the Dutch Journal of Medicine, the Medical Journal of Australia, and the Western Journal of Medicine.
Remicade prescribing information updated
Centocor in Malvern, PA, is updating the prescribing information for infliximab (Remicade), a drug used in the treatment of rheumatoid arthritis and Crohn’s disease. Developed with the U.S. Food and Drug Administration (FDA), the revised label instructs that patients should be evaluated for latent tuberculosis with a tuberculin skin test in reference to current American Thoracic Society/Centers for Disease Control and Prevention guidelines, and that treatment for latent tuberculosis should be initiated prior to therapy with Remicade. In addition, the revised label strengthens the warnings about the risk of serious infections in general, and has drawn attention to this safety information via a boxed warning.
Many of the serious infections associated with Remicade have occurred in patients on concomitant immunosuppressive therapy that, in addition to their Crohn’s disease or rheumatoid arthritis, could hinder further their infection-fighting capabilities.
The new label also addresses the risk of opportunistic infections, including histoplasmosis, listeriosis, and pneumocystis. With respect to the risk for histoplasmosis infection, the revised labeling instructs that the benefits and risks of Remicade therapy should be considered carefully for patients who have resided in a region where histoplasmosis is endemic.
Lilly, Syncor to offer three-hour Xigris delivery
Eli Lilly and Co. in Indianapolis will partner with Syncor International Corp. in Woodland Hills, CA, to provide a three-hour emergency response delivery service for drotrecogin alfa (activated) (Xigris), Lilly’s investigational biotechnology compound for the treatment of severe sepsis. Lilly’s application to market Xigris is under priority review by the Food and Drug Administration.
"We anticipate most hospitals will stock Xigris through our wholesaler network. However, if a physician needs Xigris, and it is not readily available at the hospital pharmacy, Syncor’s emergency response capabilities will ensure that physicians have rapid access," says Elaine Sorg, critical care business unit leader for Lilly.
Filmtab’ removed from Gabitril product name
Cephalon in West Chester, PA, is notifying health care professionals that it is removing the word "Filmtab" from the Gabitril (tiagabine HCl) product name. This change is a result of the acquisition of Gabitril by Cephalon from Abbott Laboratories, because the word Filmtab is a registered trademark of Abbott Laboratories. The formulation and manufacturing process of Gabitril tablets have not changed.
The change in the Gabitril product name will be reflected in all related documents (such as prescribing information and packaging material). In addition, the appearance of Gabitril tablets has been changed to replace the Abbott logo with the Cephalon logo. To view Cephalon’s "Dear Health Professional" letter, visit the web site www.fda.gov/medwatch/safety/2001/gabitril.htm.
Switching seizure meds may have risks
A study published in the Aug. 28 issue of Neurology says that switching epilepsy medications may result in either side effects or loss of seizure control for patients.
The single-dose, two-way crossover study was conducted in 24 healthy patients to determine the effect of a high-fat meal on the pharmacokinetics of generic and brand-name formulations of phenytoin. The impact of switching products on steady-state phenytoin was investigated through simulation using pharmacokinetic data previously obtained from 30 epileptic patients.
The bioavailability (the amount of the medication’s active ingredient present in the blood following a given dose) of the generic drug administered with food was 13% lower than what was observed with the brand-name drug. Simulations of substituting the generic drug for the brand-name suggest that the 13% decrease would result in a median 37% decrease in the bioavailability; in 46% of the patients, the levels of the generic drug were below the therapeutic range.
Conversely, the simulations of substituting the brand-name drug for the generic suggested a result of a median 102% increase in the bioavailability, with 84% of patients having phenytoin concentrations above the therapeutic range.
The Epilepsy Foundation in Landover, MD, says that all medical rule-making bodies should take note of this research. "The Epilepsy Foundation strongly advises that [they] address the potential adverse effects of changing from one manufacturer’s version of an epilepsy medication to another by requiring the prior expressed permission of the treating physician and patient before such medication is dispensed," says Steven Schachter, MD, associate professor of neurology at the Harvard Medical School in Cambridge, MA.
Pediatric use of Neumega should be restricted
Wyeth-Ayerst in Philadelphia is notifying health professionals of safety information for oprelvekin (Neumega) use in the pediatric population. Preliminary data from a safety and pharmacokinetic study in 47 children have identified papilledema as a dose-limiting adverse reaction in the pediatric population.
No controlled clinical studies have established a safe and effective dose of Neumega in children. Therefore, the administration of Neumega in children, particularly those younger than 12 years of age, should be restricted to controlled clinical trial settings with closely monitored safety assessments. See the full letter at this web site for further details: www.fda.gov/medwatch/safety/ 2001/neumega.htm.
Drug charges rise faster than other medical care
Prescription drug charges have increased at a faster rate than all other medical services, according to the Express Scripts’ 2000 Drug Trend Report. Between 1998 and 1999, charges for prescription drugs increased from 22.9% to 25.3% of the total charges per member per year. The rate of increase in drug spending, however, slowed slightly in 2000 to 16.2%, in part because no new blockbuster drugs were introduced. In 1999, the drug spending increase was 17.4%, primarily because of the introduction of the anti-inflammatory drugs Celebrex and Vioxx.
Factors contributing to the overall prescription drug cost increase were higher prices for existing products, use of more expensive products, stronger dosages, and more units per prescription. New drugs introduced in 2000 accounted for only 0.3% of the overall 1999-2000 trend. However, drugs introduced since 1992 accounted for approximately 47 cents of each dollar spent on prescription drugs in 2000.
The analyses contained in the report are based on claims for prescription medications for a substantial sample of Express Scripts clients. Prescriptions in this database represent drug use for a monthly average of 9.6 million members in 1999 and 8.8 million members in 2000. The report is available at: www.expressscripts.com/other/news_views/outcomes2001/outcomes_conf_2001_news_info_resource.htm.
FDA announces recall of collagenase
The Food and Drug Administration (FDA) recently announced the recall of one lot of collagenase manufactured by Advance Biofactures Corp. and sold as Santyl Ointment. The recalled lot bears the expiration date 11/2002. According to the FDA's Center for Biologics Evaluation and Research, this lot of collagenase has a lower potency than required by product specifications.
Earlier this year, two lots of Santyl Ointment were recalled because they exceeded potency specifications, and last August, one lot was recalled because testing showed it to be unsterile.
Santyl is distributed by Abbot Laboratories, which acquired the product as part of its Knoll Pharmaceuticals Co. acquisition earlier this year. The recall is occurring at the wholesale level.
Aventis Pasteur resumes restrictions on Td toxoids
On Sept. 11, Aventis Pasteur suspended filling orders for tetanus and diphtheria (Td) toxoids in an effort to respond to emergency management officials in New York and Washington, DC.
Aventis Pasteur — now the main U.S. manufacturer of Td’s — is accepting orders, but will continue to limit the distribution of Td to urgent-care facilities and hospitals nationwide.
Facilities should order in four-week supply increments to help Aventis Pasteur estimate product need. The company will ship orders from the warehouse closest to the requesting facility to minimize potential fulfillment delays.