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At least 19 recordsLinked to original sources
PubMed1991

The United States Food and Drug Administration guidelines on ambulatory blood pressure monitoring.

The United States Food and Drug Administration (FDA) does not require the use of ambulatory blood pressure monitoring in the evaluation of antihypertensive drug efficacy. It has not so far been found useful in decision-making and there is no consensus on its use. As more ambulatory blood pressure data accumulate, however, there may be a role for this technique in helping to solve particular problems in evaluating the effects of antihypertensive drugs.

Antihypertensive Agents↗
PubMed1994

FDA guidelines on trough: peak ratios in the evaluation of antihypertensive agents. United States Food and Drug Administration.

The proposed guidelines for antihypertensive drugs from the United States Food and Drug Administration (FDA) suggest that a trough: peak ratio (placebo corrected) of at least 50% should be a requisite for approval in the United States. It is apparent that many existing antihypertensive agents fail to meet this criterion. In contrast, the newer dihydropyridine calcium antagonist lacidipine has a trough:peak ratio greater than 60% which, combined with its other properties, indicates that it is suitable for once-daily administration in hypertension. There is evidence to suggest that a favorable trough:peak ratio may be beneficial in patients who are not fully compliant with the dosage regimen. In addition, a high ratio is indicative of small pharmacologically induced variability in blood pressure: indeed, lacidipine significantly reduces both systolic and mean blood pressure variability. Because blood pressure variability, independent of absolute pressure, is an important determinant of target-organ damage, there is reason to believe that agents that reduce variability may improve the morbidity associated with hypertension.

Antihypertensive Agents↗
PubMedDate not supplied

Analgesics for acute pain: Meeting the United States Food and Drug Administration's requirements for proof of efficacy.

OBJECTIVE: To examine the United States Food and Drug Administration's (FDA) standards for reviews of the scientific basis for efficacy claims for newly approved oral analgesics. METHODS: Comparison of the trial methodologies and results provided by the FDA's medical reviewer in the Summary Bases of Approval (SBA) for the 9 oral acute analgesics approved in the last 10 years: ketorolac, diclofenac potassium, bromfenac, tramadol, hydrocodone/ibuprofen fixed combination, celecoxib, rofecoxib, tramadol/acetaminophen, and valdecoxib. RESULTS: For all 9 new analgesics, studies were conducted in patients with postoperative dental pain and nondental surgical pain. The relief of gynecologic pain was examined for 5 of the new drugs. No studies in other pain models (such as infection, neuropathy, and nonsurgical trauma) supported claims of efficacy for any of the new drugs. The overall designs of the dental and nondental surgical studies, including timing of the single dose of trial drug, timing of evaluations, scales used for evaluations, and the use of both measured and derived outcome variables, were similar across the 8 development programs fully described in SBAs. Other characteristics of the trials, including choice of population for efficacy analyses, methods of carrying forward pain intensity and pain relief scores, and the length of time patients were encouraged to refrain from use of rescue medication differed across the development programs. CONCLUSION: The requirements for approval of new analgesics in the United States encourage the pharmaceutical industry to perform efficacy studies using stylized designs in dental and nondental surgical pain. Studies of the efficacy of new analgesics in other common clinical settings are rarely or never included in development programs.

Acute Disease↗
PubMed1979

The United States Food and Drug Administration and the practice of optometry.

In the past decade the United States Food and Drug Administration has become increasingly involved with the regulation of materials used in the practice of optometry. It is the purpose of this paper to help the practitioner understand the FDA involvement, historically and legally, organization, how one can have input into the process, the procedures for testing and approving new drugs and devices, their regulation and the advantages and disadvantages of such control.

History, 20th Century↗
PubMed2006

Brief report on the United States Food and Drug Administration Blood Products Advisory Committee recommendations for management of donors and units testing positive for hepatitis B virus DNA.

BACKGROUND AND OBJECTIVES: This article briefly recounts the 21st July 2005, Blood Products Advisory Committee (BPAC) meeting concerning recommendations for management of donors and units testing positive for hepatitis B virus (HBV) DNA. MATERIALS AND METHODS: The author attended the meeting. The United States Food and Drug Administration (FDA) web site was used for meeting materials, and handouts were collected at the meeting to provide narrative information. Two European experts assisted with HBV subject matter. RESULTS: The proceedings of the advisory committee, the issue briefing materials, and testing algorithms are presented. CONCLUSION: BPAC voted concurrence with the FDA algorithm for Management of Donors and Units Testing Positive for Hepatitis B Virus DNA.

Advisory Committees↗
PubMed2006

Autologous cultured chondrocytes: adverse events reported to the United States Food and Drug Administration.

BACKGROUND: Carticel is an autologous cultured chondrocyte product that has been approved by the United States Food and Drug Administration for the repair of symptomatic cartilaginous defects of the femoral condyle that are caused by acute or repetitive trauma in patients who have been previously managed with arthroscopy or other surgical procedures. The present report describes the adverse events following Carticel implantation as reported to the Food and Drug Administration from 1996 to 2003. METHODS: We reviewed adverse event reports that had been submitted to the Food and Drug Administration's MedWatch system for information on demographic characteristics, adverse events, and surgical revisions. Adverse events were categorized into sixteen non-mutually exclusive groups. Five categories were used to classify reoperations. Food and Drug Administration regulations require manufacturers to report adverse events; however, reporting by clinicians and others is voluntary. Therefore, adverse event reporting is likely to underestimate the number of event occurrences. Adverse events may be either causally or coincidentally related to the product. RESULTS: A total of 497 adverse events among 294 patients receiving Carticel were reported. The median interval from Carticel implantation to the diagnosis of an adverse event was 240 days (range, one to 2105 days). The median age of the patients was thirty-eight years, and 63% of the patients were male. Of the 270 events for which the anatomic site was noted, 258 (96%) involved the femoral condyles. More than one adverse event was reported for 135 patients (46%). The most commonly reported events were graft failure (seventy-three patients; 25%), delamination (sixty-five patients; 22%), and tissue hypertrophy (fifty-two patients; 18%). In addition, eighteen surgical site infections were reported, including eleven joint and seven soft-tissue infections. Surgical revision subsequent to Carticel implantation was mentioned in the records for 273 patients (93%). The reasons for the 389 revision procedures included graft-related problems (187 procedures; 48.1%), periarticular soft-tissue problems (ninety-seven procedures; 24.9%), and intra-articular problems (sixty-three procedures; 16.2%). Eight patients had a total knee replacement. Based on the manufacturer's reported distribution of 7500 Carticel lots between 1995 and 2002, 285 patients (3.8%) had an adverse event that was reported to the Food and Drug Administration. CONCLUSIONS: The most common adverse events reported in association with the Carticel technique involved graft failure, delamination, and tissue hypertrophy.

Adult↗
PubMed2003

End points and United States Food and Drug Administration approval of oncology drugs.

PURPOSE: To summarize the end points used by the United States Food and Drug Administration (FDA) to approve new cancer drug applications over the last 13 years. MATERIALS AND METHODS: The FDA granted marketing approval to 71 oncology drug applications between January 1, 1990, and November 1, 2002. The end points used as the approval basis for each application are presented, and the rationale for each end point is discussed. RESULTS: The FDA grants either regular marketing approval or accelerated marketing approval for oncology drug applications. Regular approval is based on end points that demonstrate that the drug provides a longer life, a better life, or a favorable effect on an established surrogate for a longer life or a better life. Accelerated approval (AA) is based on a surrogate end point that is less well established but that is reasonably likely to predict a longer or a better life. Tumor response was the approval basis in 26 of 57 regular approvals, supported by relief of tumor-specific symptoms in nine of these 26 regular approvals. Relief of tumor-specific symptoms provided critical support for approval in 13 of 57 regular approvals. Approval was based on tumor response in 12 of 14 AAs. CONCLUSION: End points other than survival were the approval basis for 68% (39 of 57) of oncology drug marketing applications granted regular approval and for all 14 applications granted accelerated approval from January 1, 1990, to November 1, 2002.

Antineoplastic Agents↗
PubMed2004

A study of warning letters issued to institutional review boards by the United States Food and Drug Administration.

PURPOSE: This study explores the ethical issues contained in warning letters (WLs) issued to institutional review boards (IRBs) by the United States Food and Drug Administration (FDA). METHODS: The online FDA Warning Letter Index was reviewed for letters issued to IRBs in the United States under the violation categories "Institutional Review Board" and "IRB" for the period January 1997 through July 2004. The resultant letters were evaluated for violations in 4 regulatory themes: having and following written procedures for research review; documentation of research review; IRB membership and conflict of interest; and informed consent. RESULTS: Fifty-two (52) FDA WLs were issued to IRBs during this period. Hospital/medical centre IRBs received the most letters (n = 34), followed by university IRBs (n = 9) and private IRBs (n = 9). The most common regulatory violations were failure to have and follow adequate written procedures about how the review of research is conducted (50 WLs); failure to prepare and maintain adequate documentation of IRB activities (47 WLs); and failure to provide adequate continuing review of approved studies (36 WLs). Nineteen WLs were issued for consent form issues. CONCLUSIONS: Warning letters are informative with regard to clinical research regulations and research subject protection. The content of these letters consistently indicates weaknesses in review and documentation activities of audited IRBs, potentially signalling similar issues among IRBs across the United States. Our findings, in a setting of overburdened IRBs who, in general, passively monitor studies, raise concerns about study oversight and optimal protection of research subjects.

Biomedical Research↗
PubMed2000

Regulatory science: a special update from the United States Food and Drug Administration: Preclinical issues and status of investigation of botanical drug products in the United States.

A recent survey was conducted across the therapeutic divisions within the CDER, U.S. FDA regarding the number of submissions related to botanical drug products over the past ten years. The overall number of botanical submissions as expressed in the parenthesis are as follows: 1990 (1), 1991 (4), 1992 (4), 1993 (5), 1994 (6), 1995 (5), 1996 (13), 1997 (16), 1998 (10). In the total of 64 counted, 50 of them are submitted in original IND and the rest (14) in pre-IND format. The therapeutic categories are focused on dermatological and topical (19), anti AIDS/antiviral (12), oncologic (13), neuropharmacologic (8), endocrine and metabolic (3), urologic (2), tobacco (2), and cardio-renal products (1). The regulatory actions taken on these submissions showed that 68% of them are evaluated as safe to proceed for the human trials, while the rest (32%) of submissions required agency's regulatory guidance. Among the submissions that required further guidance, 81% were deficient in preclinical pharmacology/toxicology information and the rest (19%) lacks information in other areas (chemistry, clinical protocols). Following agency's guidance, 93% of the submissions that were put on hold were allowed to proceed. In summary, a total of 94% of all the botanical INDs submitted to the agency were allowed to proceed without additional animal toxicity studies conducted. In conclusion, this survey indicates that the growing public interest in botanical supplements has prompted more formal evaluation of the efficacy/safety claims of these products.

Databases, Factual↗
PubMed2002

Oncology drug development: United States Food and Drug Administration perspective.

The Food and Drug Administration (FDA) in the United States has multiple roles. The primary responsibilities for oncology drug products are the supervision of clinical research, the evaluation of marketing claims for new and previously approved drugs, the granting of exclusive marketing licenses for approved claims, and the monitoring of post-marketing activity for safety. Additional roles include providing incentives for developing products for rare diseases and children. The principles used for monitoring clinical studies are based on science, law and ethical guidelines. The principles used for evaluation of evidence to support marketing claims are based in science, law, regulation, and frequently the advice of a panel of external experts. Approved products should demonstrate patient benefit that is commensurate with the probable risks. The types of endpoints and their advantages and disadvantages for regulatory review are discussed. There are regulatory options available for conditional approval based on surrogate endpoints that are likely to predict patient benefit, a mechanism for reducing the time to review an application for indications with no known effective therapy, and procedures for providing access to patients for unapproved drugs.

Antineoplastic Agents↗
PubMed1995

Ventricular fibrillation, automatic external defibrillators, and the United States Food and Drug Administration: confrontation without comprehension.

More people die in the United States each day of potentially reversible VF than of any other cause of death, reversible or not. Early defibrillation is the definitive treatment. Automated external defibrillation is a proven technology now confirmed to have saved thousands of lives. As with all medical devices and technology, perfection is not possible. Some problems, such as those represented by the two cases discussed in this article, are inevitable and acceptable and give little cause for alarm. One would not stop penicillin from being manufactured and distributed because of a sudden, unexpected allergic reaction in one patient (error of commission) or an unexpected resistant organism in another (error of omission). The FDA must understand that AEDs, even if they are imperfect, are not anywhere near as dangerous as no defibrillator at all. AEDs have finally allowed many EMS systems to achieve early defibrillation. Discontinuing use of AEDs or closing AED manufacturers could mean a significant number of lives lost unnecessarily. Therefore EMS agencies planning to implement early-defibrillation programs should continue with such plans. Why the agents of an important federal regulatory agency have singled out this technology for an intense review puzzles many observers in the medical-device field. Two meetings have been hosted by officials of the FDA to discuss the continuing concern the FDA officials have expressed over automated defibrillation technology. These meetings included representatives from the AHA, the American College of Cardiology, ACEP, defibrillator manufacturers, and other interested organizations. The FDA leadership has repeatedly focused on data acquired through the FDA Medical Device Reporting systems. Congress requires the FDA to investigate reports of problems with "critical medical devices." Because the indication for the use of a defibrillator is cardiac arrest, there will inevitably be a high association between defibrillator use and patient deaths. FDA personnel may view such reports of device problems in association with patient deaths as evidence that an intrinsically flawed technology has reached the marketplace without rigorous testing and evaluation. From the clinician's perspective, however, these reports represent a small numerator over a huge denominator of daily, lifesaving clinical use. The non-FDA participants at the two meetings have stated that the FDA complaints appear to be random and reveal a lack of understanding of AED technology.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗
PubMed2000

Update on regulatory review intervals for ophthalmic new drug applications at the United States Food and Drug Administration.

PURPOSE: To update the analysis of the regulatory review interval for ophthalmic new drug applications at the United States Food and Drug Administration for the years 1997 to 1999, based on the previous review by the author of the period 1990 to 1996. METHODS: Publicly available records on ophthalmic drugs approved by the Food and Drug Administration in this time period were reviewed. RESULTS: Of the seven ophthalmic new drug applications approved during the years 1997 to 1999, the range of approval intervals was 5 to 22 months. With only one approval in 1997, the mean was the same as that single product, 22 months. The mean approval time for 1998 was 10.3 months, and for 1999 it was 8.7 months. CONCLUSION: The ophthalmology division continues its rapid rate of New Drug Application review.

Drug Approval↗
PubMed2004

Replication of the Weber effect using postmarketing adverse event reports voluntarily submitted to the United States Food and Drug Administration.

STUDY OBJECTIVE: To validate or refute a widely accepted epidemiologic phenomenon known as the Weber effect by replicating Weber's original observation by using drugs that were marketed in the United States and using reports from a U.S. database. DESIGN: Retrospective analysis of adverse event databases. SETTING: University research center. DRUGS: The original nonsteroidal antiinflammatory drugs studied by Weber that were approved by the U.S. Food and Drug Administration (FDA) and marketed in the United States: diclofenac sodium, diclofenac potassium, diflunisal, sulindac, flurbiprofen, and piroxicam. INTERVENTION: Reports of adverse events submitted to the FDAs Spontaneous Reporting System and the Adverse Event Reporting System from January 1969-December 2000 for these drugs were analyzed according to the number of adverse events reported for each drug per year from the time the drug was approved until December 2000. MEASUREMENTS AND MAIN RESULTS: Reporting patterns were considered to demonstrate the Weber effect if the highest peak in reports during the first 5 years after product approval occurred during year 2. All five drugs analyzed in this study demonstrated the Weber effect. CONCLUSION: The Weber effect was replicable by using drugs marketed in the United States and using reports that were submitted to a U.S. database. Various other factors affected spontaneous reporting of adverse events, as peaks in the number of reports were seen numerous times for each drug after the initial 5-year marketing period.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

United States Food and Drug Administration Drug Approval summary: Gefitinib (ZD1839; Iressa) tablets.

On May 5, 2003, gefitinib (Iressa; ZD1839) 250-mg tablets (AstraZeneca Inc.) received accelerated approval by the United States Food and Drug Administration as monotherapy for patients with locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies. Information provided in this summary includes chemistry manufacturing and controls, clinical pharmacology, and clinical trial efficacy and safety results. Gefitinib is an anilinoquinazoline compound with the chemical name 4-quinazolinamine,N-(3-chloro-4-flurophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]. It has the molecular formula C(22)H(24)ClFN(4)O(3). Gefitinib is often referred to as a "specific" or "selective" inhibitor of epidermal growth factor receptor. Studies demonstrate, however, that gefitinib inhibits the activity of other intracellular transmembrane tyrosine-specific protein kinases at concentrations similar to those at which it inhibits the epidermal growth factor signal. Maximum plasma concentrations resulting from clinically relevant doses are 0.5-1 microM or more, well within the IC(50) values of several tyrosine kinases. No clinical studies have been performed that demonstrate a correlation between epidermal growth factor receptor expression and response to gefitinib. Gefitinib is 60% available after oral administration and is widely distributed throughout the body. Gefitinib is extensively metabolized in the liver by cytochrome P450 3A4 enzyme. Over a 10-day period, approximately 86% of an orally administered radioactive dose is recovered in the feces, with <4% of the dose in the urine. After daily oral administration, steady-state plasma levels are reached in 10 days and are 2-fold higher than those achieved after single doses. Gefitinib effectiveness was demonstrated in a randomized, double-blind, Phase II, multicenter trial comparing two oral doses of gefitinib (250 versus 500 mg/day). A total of 216 patients were enrolled. The 142 patients who were refractory to or intolerant of a platinum and docetaxel comprised the evaluable population for the efficacy analysis. A partial tumor response occurred in 14% (9 of 66) of patients receiving 250 mg/day gefitinib and in 8% (6 of 76) of patients receiving 500 mg/day gefitinib. The overall objective response rate (RR) for both doses combined was 10.6% (15 of 142 patients; 95% confidence interval, 6.0-16.8%). Responses were more frequent in females and in nonsmokers. The median duration of response was 7.0 months (range, 4.6-18.6+ months). Other submitted data included the results of two large trials conducted in chemotherapy-naive, stage III and IV non-small cell lung cancer patients. Patients were randomized to receive gefitinib (250 or 500 mg daily) or placebo, in combination with either gemcitabine plus cisplatin (n = 1093) or carboplatin plus paclitaxel (n = 1037). Results from this study showed no benefit (RR, time to progression, or survival) from adding gefitinib to chemotherapy. Consequently, gefinitib is only recommended for use as monotherapy. Common adverse events associated with gefitinib treatment included diarrhea, rash, acne, dry skin, nausea, and vomiting. Interstitial lung disease has been observed in patients receiving gefitinib. Worldwide, the incidence of interstitial lung disease was about 1% (2% in the Japanese post-marketing experience and about 0.3% in a United States expanded access program). Approximately one-third of the cases have been fatal. Gefitinib was approved under accelerated approval regulations on the basis of a surrogate end point, RR. No controlled gefitinib trials, to date, demonstrate a clinical benefit, such as improvement in disease-related symptoms or increased survival. Accelerated approval regulations require the sponsor to conduct additional studies to verify that gefitinib therapy produces such benefit.

Adolescent↗