Technological Innovation Comparing Development of Drugs, Devices, and Procedures in Medicine, Background Paper (1989) / Chapter Skim
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2. The Development of Drugs
2. The Development of Drugs
Pages 8-22
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From page 8... ...
On the one hand, industrial laboratories exploit basic biomedical and clinical knowledge accumulated in academic and governmental settings, including the discovery of biologically active compounds (93~. On the other hand, basic research findings are also made in industrial laboratories, whereas the availability of new drugs often permits advances in basic, non-industrial, research to be made (31~.
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; thiazide drugs for diabetes insipidus; anti-parkinson action of amantadine; antiinflammatory action of steroids and pheny~butazone; anti-gout action of abopurinol; anti-arrhythmic action of phenytoin and lidocaine; uricosuric action of probenecid; acetazolamide for glaucoma and epilepsy; diazepam for status epilepticus; protective effects of beta blockers (and the probable protective effects of platelet modulators, including aspirin) against myocardial infarction and coronary death; use of aspirin and sulfinpyrazone in preventing stroke; non surgical closure of patent ductus arteriosus in premature babies by indomethacin".
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introduced a more rational approach based on the understanding of basic biochemical and physiological processes" (109~. Following the introduction of beta-blockers into clinical practice, it was observed that beta-blockers also played a role in lowering blood pressure, preventing heart attack and coronary death.
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An 7~ Drug discovery and preclinical research is governed directly by federal Good Laboratory Practices (GEP) regulations, however, the investigational new drug regulations exert strong feedback pressures on how research is undertaken, especially to~cologica]
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The FDA classifies IND applications according to a compound's chemical type and its potential benefit, to determine priority for review. In principle, clinical trials can start 30 days after the FDA receives an IND application, unless the agency orders a "clinical hold".
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A major issue is the choice of endpoint, should one focus solely on intermediate endpoints, such as changes in biochemical, physiological and anatomical parameters, or should one also include clinical endpoints, such as effect on mortality, morbidity, or quality of life. These decisions, involving complex considerations regarding the disease, 14 This FDA study (136)
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Traditionally, a number of intermediate endpoints, such as lowering blood sugar in diabetes or lowering blood pressure in severe hypertension, have been accepted as valid by the various parties involved in drug development. In other, more recent cases involving intermediate endpoints, such as clot lysis in myocardial re-infarction or the increase of hematocrit levels in anemic dialysis patients, there has been considerable disagreement about their value.
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consisting of adequate and well-controlled investigations". Phase IT studies mostly are double-blinded, randomized controlled clinical trials.
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The scaling up for ail efficient production process, Involving pilot plant operations and various other process and quality control measures, is a crucial part of the development process. By the time an investigational drug is ready for Phase Ill studies, quite a good picture of its safety and efficacy usually has emerged, at least for a market approval decision.
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These Phase Ill studies are important in determining what wall be in a package insert for the drug and thus what market claims can be made for a new entity in advertising. There are inherent limits to how much can be known about a drug prior to its general use in everyday practice.
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essentially offers similar therapeutic benefit as already marketed drug. Orphan drugs, i.e.
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In view of rising health care costs, 3rd party payers are sometimes refusing to reimburse even the routine costs of medical care associated with clinical trials of experimental drugs.
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One approach depends on adverse effect reporting (75~. In the United States, physicians traditionally report suspected adverse effects voluntarily to the company (the FD&C Act requires manufacturers in turn to immediately report these effects to the FDA)
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in the United Kingdom in 1980, is based on this principled. In the same vein, the FDA has carried out a number of hypothesis testing studies using Medicaid and other medical record linkage data bases.
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Cohort studies, for example, may include limitations such as the exact specification of the cohorts, limited quality of the data in terms of reproducibility and validity, difficulty to analyze the attributable agents, and the occurrence of detection bias. The US Surgeon General's first report on smoking listed 5 supporting criteria to establish a cause-effect relationship: consistency of the association; temporal relationship between cause and effect; coherence with existing insights; specificity of the relationship; strength of the association.
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