Background Congress has authorized the United States Food and Drug Administration (FDA) to provide industry sponsors with a 6-month extension of drug marketing rights under the Pediatric Exclusivity ...Provision if FDA-requested pediatric drug trials are conducted. The cost and economic return of pediatric exclusivity to industry sponsors has been shown to be highly variable. We sought to determine the cost of performing pediatric exclusivity trials within a single therapeutic area and the subsequent economic return to industry sponsors. Methods We evaluated 9 orally administered antihypertensive drugs submitted to the FDA under the Pediatric Exclusivity Provision from 1997 to 2004 and obtained key elements of the clinical trial designs and operations. Estimates of the costs of performing the studies were generated and converted into after-tax cash outflow. Market sales were obtained and converted into after-tax inflows based on 6 months of additional patent protection. Net economic return and net return-to-cost ratios were determined for each drug. Results Of the 9 antihypertensive agents studied, an average of 2 studies per drug was performed, including at least 1 pharmacokinetic study and a safety and efficacy study. The median cost of completing a pharmacokinetic trial was $862,000 (range $556,000 to 1.8 million). The median cost of performing safety and efficacy trials for these agents was $4.3 million (range $2.1-12.9 million). The ratio of net economic return to cost was 17 (range 4-64.7). Conclusion We found that, within a cohort of antihypertensive drugs, the Pediatric Exclusivity Provision has generated highly variable, yet lucrative returns to industry sponsors.
In 1994, the US Food and Drug Administration (FDA) proposed an approach, based on extrapolation of efficacy findings from adults to the pediatric population, to maximize the use of adult data and ...other data when designing pediatric drug-development programs. We examined the experience of the FDA in using extrapolation to evaluate how and when it was used and any changes in scientific assumptions over time.
We reviewed 370 pediatric studies submitted to the FDA between 1998 and 2008 in response to 159 written requests (166 products) issued under the Pediatric Exclusivity Provision. We identified cases in which efficacy was extrapolated from adult data or other data, we categorized the type of pediatric data required to support extrapolation, and we determined whether the data resulted in new pediatric labeling.
Extrapolation of efficacy from adult data occurred for 82.5% of the drug products (137 of 166). Extrapolation was defined as complete for 14.5% of the products (24 of 166) and partial for 68% of them (113 of 166). Approaches to extrapolation changed over time for 19% of the therapeutic indications studied (13 of 67). When extrapolation was used, 61% of the drug products (84 of 137) obtained a new pediatric indication or extension into a new age group; this number decreased to 34% (10 of 29) when there was no extrapolation.
Extrapolating efficacy from adult data or other data to the pediatric population can streamline pediatric drug development and help to increase the number of approvals for pediatric use.
In 1997, Congress authorized the US Food and Drug Administration (FDA) to grant 6-month extensions of marketing rights through the Pediatric Exclusivity Program if industry sponsors complete ...FDA-requested pediatric trials. The program has been praised for creating incentives for studies in children and has been criticized as a "windfall" to the innovator drug industry. This critique has been a substantial part of congressional debate on the program, which is due to expire in 2007.
To quantify the economic return to industry for completing pediatric exclusivity trials.
A cohort study of programs conducted for pediatric exclusivity. Nine drugs that were granted pediatric exclusivity were selected. From the final study reports submitted to the FDA (2002-2004), key elements of the clinical trial design and study operations were obtained, and the cost of performing each study was estimated and converted into estimates of after-tax cash outflows. Three-year market sales were obtained and converted into estimates of after-tax cash inflows based on 6 months of additional market protection. Net economic return (cash inflows minus outflows) and net return-to-costs ratio (net economic return divided by cash outflows) for each product were then calculated.
Net economic return and net return-to-cost ratio.
The indications studied reflect a broad representation of the program: asthma, tumors, attention-deficit/hyperactivity disorder, hypertension, depression/generalized anxiety disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The distribution of net economic return for 6 months of exclusivity varied substantially among products (net economic return ranged from -$8.9 million to $507.9 million and net return-to-cost ratio ranged from -0.68 to 73.63).
The economic return for pediatric exclusivity is variable. As an incentive to complete much-needed clinical trials in children, pediatric exclusivity can generate lucrative returns or produce more modest returns on investment.
To develop clinical practice guidelines for cervical screening and the primary management of abnormal cytology in Ontario, using an established methodological process.
Primary data sources were ...relevant articles listed in the Medline (1998 to July 2004), Embase (1998 to July 2004), and Cochrane Library (2004, Issue 2) databases.
Studies addressing quality or the optimization of cervical screening were considered eligible in the systematic review of the evidence. Specifically, clinical practice guidelines, technology assessments, systematic reviews, and randomized controlled trials were of primary interest. Given the variability of the data, other information sources were considered eligible if there was a demonstrated gap in the published literature.
Data were identified and extracted by a methodologist and reviewed by four authors. Results were reviewed and discussed by members of an expert working group consisting of a diverse group of health professionals with expertise in cervical cancer. Data audits were conducted by independent reviewers.
recommendations with evidence ratings were developed through a review of the evidence with expert consensus and were approved by more than 80% of 40 external practitioners who reviewed the document and responded to a standardized survey.
The development of comprehensive recommendations on cervical screening in Ontario was feasible using a rigorous methodological process. Recommendations for practice are provided.
A study of 301 children who had been immunized two to 19 months previously with measles, mumps, and rubella (MMR) vaccine at 36 different sites in San Antonio, Tex, including physicians' offices and ...clinics, revealed that 99.7% had antibody against rubella and 98.3% had antibody against measles and mumps. None of the 49 infants who were tested prior to receipt of MMR vaccine had antibody against any of these viruses, indicating that the antibody found after immunization was unlikely to be due to false-positive results. The lack of antibody in these infants confirmed that there had not been a significant number of cases of these diseases that could contribute to the high frequency of antibody found after immunization. A single dose of MMR vaccine administered under customary conditions appears to be an effective method of conferring immunity against these diseases.
Eight small, premature infants developed an unusual symptom complex of pulmonary deterioration, thrombocytopenia, liver failure, ascites, and renal failure. Five infants died; the health of the other ...three infants improved and they were discharged from the hospital. This unusual syndrome occurred after introduction of a new intravenous vitamin E product (E-Ferol, alpha-tocopherol acetate) for routine use in the intensive care nursery. Even though no definite conclusion was reached as to its cause, the administration of this intravenous vitamin E product appears to be a significant risk factor.
Extract: A survey of two groups of healthy children was performed to evaluate their vitamin E status and to determine if they differed from adults with respect to plasma tocopherol concentration and ...its relationship to circulating lipids. Results indicated that 1- to 12-year-old children showed lower plasma tocopherol values with a mean of 0.59 mg/dl, compared to 0.79 mg/dl in adults. Both populations manifested linear correlations when tocopherol data were graphed as a function of blood lipid constituents. The ratio of tocopherol to total lipids, however, was significantly lower in children. Thus, the difference in tocopherol concentration cannot be explained on the basis of decreased blood lipids alone. It is concluded that the range of normality established for adults with respect to tocopherol concentrations and tocopherol/lipid ratios cannot be applied to children and that new norms need to be used in assessing pediatric patients
A measles epidemic in San Antonio, Texas provided a population of children who were immunized at less than or equal to 10 months of age and reimmunized at greater than or equal to 15 months of age. ...Of these children, 302 were evaluated for measles antibody by the sensitive enzyme-linked immunosorbent assay (ELISA), and their responses were compared with those of 300 children who had been immunized at the customary time (greater than or equal to 15 months) with a single immunization. There were only five seronegative findings in each group. The children immunized at the customary time did have significantly higher (P less than .001) antibody titers than the children immunized at less than or equal to 10 months and reimmunized at greater than or equal to 15 months. These results indicate that early immunization followed by reimmunization may be indicated when young infants are at significant risk of measles exposure. This approach should not create an increased number of serologically nonresponsive children when reimmunized at greater than or equal to 15 months.
In summary residents entering our program lacked many basic clinical laboratory skills. Without an organized curriculum in this area, residents make marginal or no gains in competence. A clinical ...laboratory program which is accessible and clinically relevant does influence residents' knowledge and skills. Whether supervised performance of tests or didactic teaching was responsible for improved test results in our residents remains to be determined. This is important to determine because of the financial restraints of most programs and the demands already present on most residents' time.
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