ABSTRACT
The low productivity and escalating costs of drug development have been well documented over the past several years. Less than 10% of new compounds that enter clinical trials ultimately make it to the market, and many more fail in the preclinical stages of development. These challenges in the "critical path" of drug development are discussed in a 2004 publication by the US Food and Drug Administration. The document emphasizes new tools and various opportunities to improve drug development. One of the opportunities recommended is the application of "model-based drug development (MBDD)." This paper discusses what constitutes the key elements of MBDD and how these elements should fit together to inform drug development strategy and decision-making.
Subject(s)
Clinical Trials as Topic/methods , Dose-Response Relationship, Drug , Drug Approval , Drug Design , Models, Biological , Pharmacology , Research Design , Alzheimer Disease/drug therapy , Alzheimer Disease/psychology , Amines/pharmacology , Amines/therapeutic use , Analgesics/pharmacology , Analgesics/therapeutic use , Animals , Anticholesteremic Agents/pharmacology , Anticholesteremic Agents/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Caproates/pharmacology , Caproates/therapeutic use , Cholesterol/blood , Clinical Trials as Topic/legislation & jurisprudence , Clinical Trials as Topic/statistics & numerical data , Cognition/drug effects , Computer Simulation , Cyclohexanecarboxylic Acids/pharmacology , Cyclohexanecarboxylic Acids/therapeutic use , Gabapentin , Glycoproteins/pharmacology , Glycoproteins/therapeutic use , Guidelines as Topic , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/blood , Hypercholesterolemia/drug therapy , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Meta-Analysis as Topic , Models, Statistical , Muscarinic Agonists/pharmacology , Muscarinic Agonists/therapeutic use , Neuralgia, Postherpetic/drug therapy , Neutrophil Infiltration/drug effects , Oximes/pharmacology , Oximes/therapeutic use , Pharmacokinetics , Reproducibility of Results , Stroke/drug therapy , Stroke/immunology , United States , United States Food and Drug Administration , gamma-Aminobutyric Acid/pharmacology , gamma-Aminobutyric Acid/therapeutic useABSTRACT
The effect of a greater volume of patients with similar conditions being treated at a hospital on the outcomes achieved is studied using a variety of categories of patients, 15 surgical and 2 medical, and involving 550,000 patients treated in over 1,200 nonfederal United States acute care hospitals. After demonstrating that there are significant differences in the outcomes of patients, taking into account patient health status, the authors examine the impact of being treated in a hospital with a high or low volume of similar patients. Strong and consistent evidence is found that high volume is associated with better outcomes for surgical patients, which supports regionalizing patient care by procedure. Two additional variables, relative difficulty of the procedure and risk level of the patients, are analyzed to determine whether they change the relationship between volume and outcome. Some evidence is found that low-volume hospitals are associated with the poorest outcome for low-risk surgical patients. The evidence for medical patients is weak and mixed. Possible alternative explanations for the observed findings for surgical and medical patients are discussed.
Subject(s)
Hospitals/statistics & numerical data , Outcome and Process Assessment, Health Care , Female , Humans , Male , Regional Medical Programs , Risk , Statistics as Topic , Surgical Procedures, Operative/mortality , United StatesABSTRACT
The effect of a greater volume of patients with similar conditions being treated at a hospital on the outcomes achieved is investigated for almost 500,000 selected surgical and medical patients treated in over 1,200 nonfederal United States hospitals. In Part I the authors found strong and consistent evidence for surgical patients that high volume is associated with better outcome; evidence for medical patients was mixed. In this paper the authors include other hospital variables related both to volume and outcome--hospital size, teaching status, and expenditures--to determine whether they mask the true relationship; still, strong and consistent evidence that greater volume produces better outcome was found for both surgical and medical patients. This relation was significant for low-, medium-, and high-risk patients. Among the hospital variations added, only size was consistently and strongly related to outcome; greater size was associated with poorer outcome after accounting for volume. The potential importance of the findings for reducing deaths and days in hospital on a national level is discussed. The evidence is strongly supportive of the need for policies that would promote greater regionalization of a given service, and not greater size, to obtain better quality outcome for patients treated.
Subject(s)
Hospitals/statistics & numerical data , Outcome and Process Assessment, Health Care , Bed Occupancy , Health Expenditures , Hospital Bed Capacity , Hospitals, Teaching/statistics & numerical data , Humans , Regional Medical Programs , Regression Analysis , Risk , Surgical Procedures, Operative/mortality , United StatesABSTRACT
In this research, we examine the relative importance of different structural units in a professional organization, the hospital, as they affect organizational effectiveness. The difficulties of measuring effectiveness in a complex professional organization are discussed, and an adjusted measure of surgical outcome is developed. Data are drawn from a prospective study of over 8,000 surgical patients treated by more than 500 surgeons in 15 hospitals throughout the nation. Two different types of analyses are presented, both indicating that hospital features have more impact on surgical outcomes than do surgeon characteristics. The second analysis assesses the relative importance of specific attributes of the hospital, surgical staff organization, and surgeon characteristics on surgical outcomes.
Subject(s)
General Surgery , Hospital Departments/organization & administration , Quality of Health Care , Surgery Department, Hospital/organization & administration , Costs and Cost Analysis , General Surgery/standards , Institutional Practice/organization & administration , Management Audit , Outcome and Process Assessment, Health Care , Prospective Studies , Specialties, Surgical , Statistics as Topic , United StatesABSTRACT
Characteristics of hospitals may be useful predictors of the economy, efficiency, and effectiveness of services delivered. But it is difficult to explain the variables of cost and quality among hospitals until differences among patients and outcomes are accounted for. A promising new research approach is explored as a source of information on that most elusive of all measures in service organizations--the outcome experienced by clients.
