The doctrine of informed consent is fundamental to all medical personnel involved in investigational research. Informed consent arose from the Helsinki declaration that stated, “concern for the interests of the subject must always prevail over the interests of science and society.” (6) As clinical research is a part of medical practice, it is reasonable to assume that exceptions to fully informed consent that are defendable in medical practice can be applied to clinical research as well. The exceptions to fully informed consent are waiver, incompetence, therapeutic priviledge, emergency, or proxy.
The FDA's Spontaneous Reporting System (SRS) has unique public health utility in monitoring drug safety but its functioning requires attention to encourage physician participation. The State of Maryland undertook an FDA-sponsored project to promote direct physician reporting in 1985. During the first year, intervention consisted of education and a telephone reporting service. The effect of the intervention was evaluated by survey. Knowledge of the FDA-SRS increased (p<.001) but no statistically significant difference in reporting between study and control groups was observed. However, overall state reporting increased four-fold over the previous year's performance (p<.001). In the project's second year, a hospital network was added before funding for the Maryland project was unexpectedly discontinued. The project concludes that physician reporting can be encouraged but that any program directed at accomplishing this objective must have long range planning, a guaranteed source of funding, and employ a wide array of strategies.
In an effort to understand physician behavior in reporting adverse drug reactions (ADRs) and to assess ways to improve direct reporting of ADRs, the FDA initiated a contract research program through state health departments in 1985. Maryland and Rhode Island were awarded the first two pilot test contracts to survey physicians' existing attitudes and to design interventions to promote and increase ADR reporting. To investigate the feasibility of increasing ADR reporting within hospitals, a third pilot contract was awarded to Mississippi in 1986. In 1987, Massachusetts and Colorado were awarded contracts to use and build on the interventions developed by the first three states. The program has been successful in stimulating the reporting of ADRs by physicians. However, ongoing interventions are needed to sustain the higher reporting rates. Ideally, five to six ADR reporting centers in different geographic regions should be established nationally.
Physician knowledge and attitudes relating to the spontaneous reporting of adverse drug reactions (ADRs) were investigated using a survey of Rhode Island physicians. The survey confirmed physician underutilization of the FDA reporting system. Respondents (75% response rate) displayed a poor knowledge and understanding of the system. A lack of availability of report forms, lack of certainty the drug caused the reaction, and a previous knowledge of the reaction were identified as the major impediments to reporting. Two years later, after the Rhode Island Department of Health implemented various interventions, physicians were resurveyed. At this time, respondents (69% response rate) displayed an improved knowledge and understanding of the ADR reporting system. Compared with the baseline survey all the major impediments, except for lack of certainty the drug caused the reaction, were dramatically reduced. Concern about legal liability and the time involved in reporting were important to a greater percentage of follow-up respondents than baseline respondents.
Computer simulations were used to evaluate the truncated area under the plasma level-time curves (AUC.) as indicators of the bioequivalence between test and reference products. Plasma concentrations were simulated from one and two compartment open models using first order absorption rate constants (Ka) and bioavailability (F) ranging respectively from 45 to 200% and 60 to 140% of the reference values. The pharmacokinetic parameters were selected to cover a wide range of disposition rate constants (0.01-0.79 hr.−1). The area under the blood level-time curves was calculated using the trapezoidal rule at each time point (t) according to a conventional sampling regimen. The extent of absorption (AUC.inf) was calculated, using integrals of the general blood equations. The ratios of AUC.: test to reference and AUCL to AUC.were determined. For most simulations, the ratios changed very little between the end of the absorption period, the last time point and the time infinity. AUC, was not a good parameter to compare the bioavailability of two drug products. Three groups of different mathematical behavior were identified, in which bioequivalence determination might present some problems when using a single AUC. Several truncated AUC ratios, however, could provide meaningful information on absorption rates for bioequivalence testing. In our study the AUC80 was consistently a good indicator of bioequivalence.
The Mississippi Adverse Drug Reaction Reporting Program was instituted in 1986 and is to be funded through 1992. The project was designed to stimulate the reporting of ADRs on a statewide basis. The project has been successful in increasing the numbers of ADRs reported from Mississippi, as well as enhancing the awareness of the positive features inherent in the reporting of ADRs externally from practitioners' practice sites. The project has encompassed a community and hospital component throughout. This manuscript lists activities to date, the analyses accomplished to analyze data derived from the project, and plans for the remaining three years of the project.
Concern for outside review of medical research involving human subjects has been documented as far back as the early Nineteenth Century. It was not until 1966, however, when applicants for Public Health Service grant funding were subjected to such a requirement, that researchers were required to undergo review. Institutional Review Boards (IRB) and Noninstitutional Review Boards (NRB) are the bodies charged with performing the mandated screening functions by the Department of Health and Human Services (HHS) for federally funded projects and by the Food and Drug Administration (FDA) in the drug and device approval process.This paper explores Board responsibilities under the HHS and FDA regulations generally, and emphasizes several critical attendant issues including: Manufacturer'-Boards members' individual liability; compensation for research injuries; civil rights protections afforded subjects; impact upon academic and health practitioner research; and effect upon drug and device approvals.
The Food and Drug Administration (FDA) has maintained a spontaneous voluntary system for the reporting of adverse drug events for over three decades. Based on the experience of the American Medical Association Registry for drug-related aplastic anemia, the current FDA spontaneous reporting system (FDA-SRS) was initiated in response to the public reaction to thalidomide induced phocomelia (1). A serious omission of the system has been a lack of focus on ADR observations by the health care provider. The Massachusetts Division of Food and Drugs was selected to participate in the pilot projects to promote reporting of adverse drug events. The Massachusetts Adverse Drug Reaction Project tried to increase the quantity and quality of adverse drug reaction reports filed by physicians. The basic focus of the project was to utilize various promotional mechanisms to convince providers that ADR reporting is an important public health safeguard. The project also attempted to facilitate access to reporting mechanisms.
The classical compartmental analysis and the curve fitting procedure provide appropriate representations of pharmacokinetics of drugs. However, in the case of drugs given with a carrier, the interpretation of the calculated data may often be ill-defined due to the method of measurement of the concentration in the plasma or their physical adsorption or desorption. One of the relevant
Biotechnology is defined as biology-based technology using organisms or their parts to make or modify products or to improve characteristics of plants, animals, and microorganisms for the demands of human beings. Biotechnology profoundly impacts various fields such as agriculture, animal husbandry and veterinary, industry, food science, pharmaceutics and medicine, environment, fine chemistry, biofuels, forensics, and nanotechnology. Nowadays, biotechnology and bioindustries are becoming integral parts of the knowledge-based economy, and therefore, biotechnology has become a powerful and indispensable tool for the development of all countries in the world. As a rule, biotechnology also requires regulatory policies to control genetically modified organisms and derived products to avoid risks to biodiversity, human health, the environment, and ethical issues. This article reviews the current research, challenges, and perspectives of biotechnology as an integration of both life sciences and applied sciences.
Home health care is one of the fastest growing segments of the health care delivery system in the United States. The scope of medications administered in the home setting have expanded from traditional TPNs and chronic pain manage-ment to include dopamine infusions and other medications previously reserved to the hospital setting. However, little information is available regarding the adverse drug reactions (ADRs) encountered in the home infusion environment, including the degree of severity, the incidence and the patient outcome. Establishing an effective ADR program in the home setting may optimize patient safety and provide valuable information regarding the nature and significance of reactions that occur in this population.The University of Rhode Island has established a dedicated phone line which enables home health care pharmacists to monitor and report ADRs. After 13 months of operation, 125 adverse drug reaction reports were received by the center from two national home infusion providers.
Alzheimer’s disease (AD) is the most common cause of dementia. In the United States, an estimated 5.3 million people had AD dementia in 2015, including 200,000 individuals younger than age 65 years. The number of people who are affected by AD is projected to reach 16 million in 2050. There is a tremendous cost associated with caring for people with AD. In 2015, the direct costs to US society of caring for those with AD totaled an estimated $226 billion, and if no effective disease-modifying treatments become available, this could increase to $1.1 trillion in 2050. In addition to medical costs, in 2014, caregivers of people with AD and other dementias provided an estimated 17.9 billion hours of unpaid assistance, which translates to a value of $217.7 billion. Therefore, cognitive enhancers for AD by improving cognition could address symptoms associated with AD, reduce caregiver burden, and limit health care costs.
