"A temporary moratorium on DTC advertising of prescribed drugs and medical devices will benefit both the patient and physician," said Ronald M. Davis, MD, AMA president-elect. "Physicians will have the opportunity to become better educated on the pros and cons of prescription drug uses before prescribing them, and will be better able to determine when they are best suited for their patients' medical needs."
In addition, the group's guidelines recommend that such ads:
• should provide objective information about drug benefits that reflect the true efficacy of the drug, as determined by clinical trials;
• should show fair balance between the benefits and risks of the advertised drugs by providing comparable time or space and cognitive accessibility, and by presenting warnings, precautions and potential adverse reactions in a clear and understandable way without distraction of content;
• should clearly indicate that the ad is for a prescription drug and refer patients to their physician for more information and appropriate treatment;
• should be targeted for age-appropriate audiences; and
• should receive pre-approval from the FDA.
The AMA also calls for additional research into the effects of DTC advertising on the patient-physician relationship, overall health outcomes and health-care costs.
"The AMA will work with the pharmaceutical industry for universal acceptance of the guidelines so that physicians can help patients obtain appropriate medications," said Dr. Davis.
First-line Approval For Lumigan
The FDA approved Allergan's once-daily prescription eye drop Lumigan (bimatoprost ophthalmic solution) 0.03% as a first-line treatment for elevated intraocular pressure associated with open-angle glaucoma or ocular hypertension. The first-line indication is in addition to the product's established use as a second-line treatment.
"This first-line indication supports the initial use of Lumigan to lower elevated IOP associated with open-angle glaucoma or ocular hypertension," said Scott Whitcup, MD, Allergan's executive vice president of Research and Development. "We are pleased to offer eye-care professionals this effective therapy to treat elevated IOP in their glaucoma patients at any point in the course of the disease."
The FDA approved Lumigan in 2001 as an IOP-lowering medication for second-line use. "The FDA's first-line indication helps to validate that the lipid class of medications has become the mainstay of IOP-lowering therapy and that once-a-day lipids are becoming the therapy of choice based on their efficacy, systemic safety and ease of use," said Paul P. Lee, MD, JD, professor of ophthalmology at Duke University.
Study Discounts Antioxidant/Cataract Connection
Antioxidant supplementation with ß carotene, vitamins C and E did not affect cataract progression in a population with a high prevalence of cataract whose diet is generally deficient in antioxidants, according to a recent report in the British Journal of Ophthalmology.
The five-year Antioxidants in Prevention of Cataracts Study (APCS) is the first prospective interventional trial for cataract prevention to take place in a developing country and includes baseline cataract evaluation. Investigators enrolled 798 subjects and looked at effects of antioxidant supplements on cataract progression in rural South India. The primary outcome variable was change in nuclear opalescence over time in the randomized, triple-masked (meaning the biostatistician is also masked, along with the subjects and investigators), placebo-controlled, field-based clinical trial.
Secondary outcome variables were cortical and posterior subcapsular opacities and nuclear color changes; best corrected visual acuity change; myopic shift; and failure of treatment. Annual examinations were performed for each subject by three examiners, in a masked fashion. Multivariate modeling using a general estimating equation was used for analysis of results, correcting for multiple measurements over time.
There was high compliance with follow-up and study medications. There was progression in cataracts. There was no significant difference between placebo and active treatment groups for either the primary or secondary outcome variables.
In India, there may be earlier development and more rapid progression of cataracts than in other regions. Despite efforts to increase availability of high-quality surgery with acceptable visual outcomes, there is still a growing backlog of patients who are blind from cataracts. If a practical, large-scale intervention could slow the onset of cataract by 10 years, the need for cataract surgery would be decreased by 45 percent. This would have a profound effect on the increasing backlog of patients who cannot be reached by surgery given the available resources.
Although the majority of epidemiological studies have shown a positive correlation between higher dietary antioxidant intake and decreased cataract formation, conflicting conclusions exist. Also, as studies on ß carotene and lung cancer have shown, epidemiological evidence does not guarantee positive findings in interventional studies. This study, based in five villages surrounding Madurai, Tamil Nadu, India, was a collaboration between the Aravind Eye Hospital in Madurai, India, and the Francis I. Proctor Foundation for Research, in San Francisco.
Inclusion criteria were age 35 to 50 years, BCVA of 20/40 or better in both eyes, and no history of diabetes mellitus, intraocular surgery, radiation therapy, corticosteroid therapy or active use of vitamin supplements. The relatively young age was included because of the early progression of cataracts in south India.
Compliance with the study medication was excellent with 90.1 percent of subjects receiving 95 percent of the intended doses and an additional 6.1 percent of subjects receiving between 90 and <95 percent of their intended doses. Only 0.8 percent of subjects received <85 percent of intended tablets. There were no differences in compliance based on sex (p=0.55) or age (p=0.71) of subjects.
The intervention doses of antioxidant vitamins given in the APC study exceeded the U.S. recommended minimum daily allowance of 5,000 IU for vitamin A, 60 mg for vitamin C, and 30 IU for vitamin E. The U.S. recommended minimum daily allowance, however, is based on the minimal dose required to avoid vitamin deficiency diseases. The "optimal" dose of vitamins for maximum health has not been established.
The study demonstrated no effect of the antioxidants ß carotene and vitamins E and C on cataract progression. The findings, while negative, are important, the authors say, because previously it was not known whether intervention with vitamin C, E, and A supplements could decrease cataract formation in this setting. The fact that this study was negative in a population that may have been most likely to benefit from intervention (one in which the dietary antioxidant intake is low) should put to rest thoughts that ß carotene and vitamins C and E, in isolation, can influence cataract progression, they conclude. The model used to test this intervention was robust and could be applied to other interventions to assess cataract prevention. This study also demonstrates that a long-term clinical trial performed in rural south India can have excellent follow up and robust data and results.
Phase IV Macugen Maintenance Trial Launched
OSI Pharmaceuticals and Pfizer announced the initiation of LEVEL (EvaLuation of Efficacy and safety in maintaining Visual acuity with sEquential treatment of neovascuLar AMD), a Phase IV trial that will explore the safety and efficacy of Macugen (pegaptanib sodium injection) as a maintenance therapy for patients who have received prior neovascular AMD treatment and experienced improvement in macular disease. The 54-week trial, comprising up to 1,000 patients at 100 sites across the country, was scheduled to begin enrollment in late June.
Nearly 70,000 patients have already been treated with Macugen, according to the manufacturer. Safety may be an important consideration when choosing a maintenance therapy. According to retrospective Medicare data presented at the annual meeting of the Association for Research in Vision and Ophthalmology, patients with neovascular AMD are typically older, with significantly more co-morbid conditions such as hypertension, diabetes, lipid disorders, stroke and heart attack than those who do not have neovascular AMD.
"Armed with a growing number of treatment options, we should explore new regimens that may be capable of providing beneficial patient outcomes while addressing long-term safety and dosing considerations," said Thomas R. Friberg, MS, MD, professor of Ophthalmology and Bioengineering at University of Pittsburgh Medical Center and a lead investigator in the LEVEL trial. "For example, clinical data suggest that a non-selective anti-VEGF-A therapy can improve vision in a significant portion of patients and that this improvement may stabilize after a few injections. It makes sense to study whether these gains can also be maintained using a selective anti-VEGF therapy."
By specifically targeting and suppressing vascular endothelial growth factor 165, Macugen has been shown to reduce blood vessel growth and preserve vision by slowing vision loss. In addition, Macugen has an excellent long-term safety profile that has been evaluated in controlled clinical trials up to two years. Patients were then followed for a third year of treatment in an uncontrolled extension study.
In this open label, multicenter trial, subjects must have had at least one, but no more than three treatments for neovascular AMD within 30 to 120 days prior to study entry leading to an improvement in macular disease. Macugen will be administered once every six weeks for 48 weeks. Booster treatment with additional neovascular AMD therapy may be employed if the investigator believes macular disease has progressed.
The primary endpoint is the percentage of subjects who remain at baseline vision or gain (> 0 lines) vision from baseline to 54 weeks. Secondary endpoints include the percentage of subjects maintaining or gaining one, two and three lines of visual acuity at week 54 compared to pre-enrollment baseline vision (treatment initiation baseline); the mean change of visual acuity from baseline to week 54; the percentage of subjects losing less than three lines of vision at 54 weeks; and anatomical outcomes on fluorescein angiography and optical coherence tomography.
