From idea to market: the drug approval process. (25/767)

BACKGROUND: Each year many new prescription drugs are approved by the Food and Drug Administration (FDA). The process of developing and bringing new drugs to market is important for primary care physicians to understand. METHODS: We describe the drug development process based on a review of the literature and Web sites addressing FDA processes and policies. RESULTS: The process starts with preclinical testing. For drugs that appear safe, an investigational new drug application is filed with the FDA. If approved, clinical trials begin with phase 1 studies that focus on safety and pharmacology. Phase 2 studies examine the effectiveness of the compound. Phase 3 is the final step before submitting a new drug application (NDA) to the FDA. An NDA contains all the information obtained during all phases of testing. Phase 4 studies, or postmarketing studies, are conducted after a product is approved. Recent changes in legislation have streamlined the approval process. Critics contend that these changes have compromised public safety, resulting in the need to recall several products from the market. Proponents claim that changes in the approval process help patients with debilitating diseases, such as acquired immunodeficiency syndrome, that were previously denied critical medication because of bureaucratic regulations.  (+info)

A cost-effectiveness approach to drug subsidy and pricing in Australia. (26/767)

The Australian government offers its citizens subsidies on a select list of pharmaceuticals. For a drug to qualify for inclusion on this list, its manufacturer must demonstrate that the drug is both clinically effective and cost-effective. In part, this measure, along with others, was introduced to improve clinical and economic outcomes. Although this evidence-based system has provided transparency and consistency in decision making about which drugs will be covered, it may not have contained the rate of increase in drug costs.  (+info)

Participation of women in clinical trials of drug therapies: a context for the controversies. (27/767)

Women's participation in clinical trials, particularly those involving drugs, has been said to be both overrepresented and underrepresented. How can this be? Studies of participation are compared and contrasted to elucidate some reasons for this contradiction. The history of women's participation in clinical trials is chronicled through policies and regulations filled with restrictions. Since 1993, however, the National Institutes of Health has mandated, and the Food and Drug Administration has emphasized, inclusion of women in clinical trials, only to be thwarted by other regulations excluding many women. Gender-specific analyses are required to detect gender differences in effects of pharmaceutical and nonpharmaceutical interventions, but they are seldom performed. The exclusion of women from clinical trials means that women's healthcare is compromised by lack of sex-specific information about dosing of drugs and unique uses of drugs. A database, although currently quite limited, tracks the participation of women in clinical trials funded by federal agencies, industries, and nonprofit groups. Federal regulations have recently changed. Additional changes in access to all phases of clinical trials and enhanced monitoring of clinical trials are recommended.  (+info)

Chlorproguanil-dapsone (LAPDAP) for uncomplicated falciparum malaria. (28/767)

The synergistic antifolate combination of chlorproguanil with dapsone (CPG-DDS; LAPDAP) is being developed by a public-private partnership as a low-cost treatment for uncomplicated falciparum malaria. LAPDAP is rapidly eliminated from the body, giving it low selection pressure for drug resistance. Clinical cases with sulphadoxine-pyrimethamine (SP)-resistant infections acquired in Africa have been predicted to be responsive to LAPDAP, and clinical evidence is available to support this. A regulatory dossier is being prepared for simultaneous submission to the UK Medicines Control Agency and African licencing authorities. The team working on LAPDAP has also started to develop the triple combination of chlorproguanil-dapsone-artesunate (CDA) as a low-cost combination therapy for uncomplicated falciparum malaria. Although LAPDAP does not have regulatory approval (and development of CDA is at an early stage), the development team is keen to communicate with public health scientists to try to anticipate the policy and implementation hurdles that lie ahead. This short paper outlines the current stages that LAPDAP and CDA have reached, and sketches the anticipated public health issues.  (+info)

Challenges in the development, licensure, and use of combination vaccines. (29/767)

Before substantial public health benefits associated with use of combination vaccines can be realized, a variety of challenges must be addressed. In February 2000, the National Vaccine Program Office convened the International Symposium on Combination Vaccines to explore solutions for barriers to development, licensure, and use of safe and effective combination vaccines. The symposium focused on the following questions: (1) What immunologic standards should be used to evaluate new combination vaccines? (2) How should correlates of protection be developed, and how should the data they provide be interpreted? (3) What sample size is adequate for prelicensure safety trials of combination vaccines? (4) Should standards for evaluation of combination vaccines containing licensed components be different from standards for evaluation of combinations containing unlicensed components? (5) How can the "great expectations" of postlicensure surveillance be realized? Available data relevant to these issues were presented, providing a foundation for furthering the science of combination vaccines.  (+info)

Prelicensure evaluation of combination vaccines. (30/767)

There is considerable public health interest in licensing safe and effective combination vaccines. Because combination vaccines may progress rapidly from phase 1 to a pivotal phase 2 immunogenicity trial, a rigorous approach to address product issues early in development is warranted. Clinical studies to evaluate the safety, immunogenicity, and (when necessary) clinical end point efficacy of combination vaccines should be randomized and well controlled in most cases. A large phase 3 safety study (i.e., a study that enrolls thousands of vaccinees) should be included in the development plan if a phase 3 (clinical end point) efficacy trial will not be conducted. Often, the new combination vaccine under development contains immunogens that have all been previously licensed, have demonstrated efficacy in earlier clinical trials, or both. For such products, comparative immunogenicity data may be sufficient to support efficacy. When applicable, clinical data to support simultaneous administration with other relevant vaccines should be obtained. Given the complexity of combination vaccine development, early consultation with United States Food and Drug Administration can be invaluable.  (+info)

Assessing efficacy of Haemophilus influenzae type b combination vaccines. (31/767)

Regulatory approval of diphtheria and tetanus toxoids and acellular pertussis (DTaP)-based combination vaccines containing Haemophilus influenzae type b (Hib) has been delayed in the US because of difficulty in assessing the effect of lower Hib immunogenicity on vaccine efficacy compared with the immunogenicity of the specific Hib component administered separately. Hib conjugate vaccines confer protection by eliciting serum anticapsular antibody and priming for immunologic memory. Therefore, compelling proof of efficacy would be demonstration that a combination vaccine primes for memory and elicits antibody responses that are not inferior to those elicited by other US-licensed Hib conjugate vaccines, not necessarily the specific Hib component used in the combination. Vaccinated infants also can be considered protected if their serum anticapsular antibody concentrations are > or =0.15 microg/mL immediately before the booster dose given in the second year of life, when antibody concentrations are lowest. These alternative serologic approaches offer a strong scientific and regulatory rationale for licensure of effective DTaP-based Hib combination vaccines.  (+info)

Evaluating the immune response to combination vaccines. (32/767)

Assessment of the immune responses to combination vaccines in the United States has generally been based on randomized, controlled comparative trials, with such studies designed to rule out predefined differences. In designing clinical studies of the immune response to combination products, attention should be directed toward selecting the appropriate immunologic end points and control groups. Acceptable differences in immune responses between combination and control groups should be predefined, and an adequate statistical plan should be developed. In many cases, it may be necessary to evaluate simultaneous administration of other recommended vaccines, assess schedule changes for 1 or more components of a combination, and bridge immunologic data obtained from international studies to the population of the United States. We discuss the use of immunogenicity studies to support the licensure of combination vaccines when field efficacy studies are either not possible or not required and highlight some recent experiences with combination vaccines containing Haemophilus influenzae type b polysaccharide conjugates.  (+info)