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Biomedical subjects

G R Venning

Publications and source records attributed to G R Venning.

At least 19 recordsLinked to original sources
PubMed1992

AIDS and activists.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1992

New drug treatments for HIV infection and AIDS. A review following the Seventh International Conference on AIDS, Florence 16-21 June 1991.

1. OBJECTIVE--To evaluate the status of clinical development of zidovudine and new drugs for the treatment of Human Immunodeficiency Virus (HIV) infections. 2. METHOD--A critical review of the clinical trial reports and assessment of the design and methodology of the therapeutic trials. Evaluation of the drugs being tested and of the specific difficulties in testing drugs in AIDS. 3. CONCLUSIONS--Drugs are being tested in a unique climate of public opinion characterised by (1) fast track criteria for regulatory approval (2) parallel track (compassionate release) of new drugs before adequate determination of safety and efficacy (3) resistance to the use of placebos in controlled trials.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Priorities in the benefit-risk assessment of new drugs.

With the present emphasis on animal safety data, human benefit and risk may be inadequately quantified at the clinical trial stage and the assessment of risk from adverse reaction reporting is also based on methods that lack epidemiological precision. Under these conditions there must be serious doubts about the accuracy of assessment of some of the new drugs that come under suspicion. Suggestions have been made for improving the situation. A closer scrutiny of human data at the clinical trial stage, while involving some increase in the requirements for clinical trial data, would be advantageous for the pharmaceutical industry as well as for other interested parties if it were part of a deliberate change of emphasis from animal to human evidence of safety and from absolute to relative efficacy data in the assessment of product licenses.

Animals↗
PubMed1983

Identification of adverse reactions to new drugs. IV--Verification of suspected adverse reactions.

The verification processes were assessed for 18 important adverse drug reactions. Verification when achieved by formal studies was not obtained through cohort studies such as postmarketing surveillance or other follow up of drug users but through case-control studies or a similar disease orientated approach. When not achieved in this way the most useful aspects of uncontrolled studies were rechallenge and dose-response data. Analysis of the data and of the characteristics of different methods of verification suggested that there were four approaches to earlier discovery. (1) The best system seemed to be some form of record linkage, capable of providing at the same time data on incidence of adverse reactions and on prevalence of drug usage in patients with disease suspected of being drug induced. Until such a system can be established the relative efficacy of alternative approaches appears to be (2) review of all published first alerts, with prompt initiation of case-control or disease orientated studies for verification, (3) postmarketing surveillance of cohorts of drug users, and (4) voluntary reporting systems.

Clinical Trials as Topic↗
PubMed1983

Identification of adverse reactions to new drugs. III: Alerting processes and early warning systems.

The process of discovery for 18 important adverse drug reactions was analysed in terms of study designs and other features which determined whether published reports of suspected adverse reactions were convincing or provided valid evidence of causality. First alerts were almost always anecdotal reports. For earlier alerting during clinical trials event recording is needed, associated with dose-response data and the use of patients as their own controls.

Australia↗
PubMed1983

Identification of adverse reactions to new drugs. II--How were 18 important adverse reactions discovered and with what delays?

The process of discovery of 18 important adverse drug reactions was reviewed. For each adverse reaction the dates were noted of the report which first alerted the medical profession to the suspected reaction, the report which resulted in verification of causality beyond reasonable doubt, and the first regulatory action or warning to the medical profession in Britain by the Committee on the Safety of Medicines.

Chloramphenicol↗
PubMed1983

Identification of adverse reactions to new drugs. I: What have been the important adverse reactions since thalidomide?

A consensus process was used to establish an agreed list of important adverse reactions to drugs identified since thalidomide. Ten physicians working in medicine in Britain and 10 physicians responsible for drug regulatory agencies in different countries were asked to list 10 important adverse reactions to drugs since thalidomide. From these 20 lists a measure of agreement was apparent. Eighteen important adverse reactions were identified for further study of the discovery processes now operating and of the delays occurring from marketing to alerting, from alerting to verification, and from verification to regulatory action. The results suggest that an empirical review of this type is necessary as a starting point for discussion of better systems to reduce delays in the discovery of adverse reactions to new drugs.

Drug Evaluation↗
PubMed1982

Validity of anecdotal reports of suspected adverse drug reactions: the problem of false alarms.

Suspected adverse drug reactions first reported in 1963 in the "British Medical Journal," the "Lancet," the "Journal of the American Medical Association," and the "New England Journal of Medicine" were reviewed 18 years later to assess their initial validity and subsequent verification. Of 52 first reports, five were deliberate investigations into potential or predictable reactions, and in each case causality was reasonably established; the other 47 reports were essentially anecdotal. Of these 47 reports, 14 related to categories of adverse reaction where false-positive reports were unlikely: immediate reactions, local reactions, and known reactions caused by a different mode of administration or a brand previously thought or claimed to be safe. The problem of false alarms rose in the remaining types of reactions: general reactions that did not occur immediately after administration and arose for the first time with a new chemical entity. Of 33 reports of such suspected adverse reactions, validity was satisfactorily established in 14 cases on the basis of rechallenge, predictability from known pharmacology, or the unique nature of the reaction. Of the remaining 19 reports, further verification still has not been satisfactorily established in 12. Seven of these possible false alarms were haematological reactions.Although 35 of the 47 anecdotal reports were clearly correct, of the 19 reports that were not reasonably validated at the time of the report, only seven were subsequently verified. This suggests that agencies monitoring adverse drug reactions should adopt criteria for assessing the validity of first reports of suspected adverse reactions. Such criteria should include: reactions on rechallenge, a pharmacological basis for the adverse reaction, immediate acute reactions, local reactions at the site of administration, reactions with a new route of administration of a drug known to provoke such reactions by another route, and the repeated occurrence of very rare events.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1982

Relative potency and structure activity relationships of aldosterone antagonists in healthy man: correlation with animal experience.

1 The renal antimineralocorticoid potency of single doses of thirteen compounds with properties in animals compatible with competitive aldosterone antagonism was compared to that of spironolactone in healthy men. 2 Twelve compounds showed significant activity when compared to placebo but only one, prorenoate potassium, was significantly more potent than spironolactone on a weight basis. 3 The results allowed ranking of the compounds in order of potency relative to spironolactone and general observations on structure activity relationships in man. 4 Animal bioassays and in vitro aldosterone binding studies are unreliable predictors of the human activity of competitive mineralocorticoid antagonists.

Animals↗
PubMed1981

Bioassay of a new aldosterone antagonist and evaluation of a simple method of quantitative comparison.

The renal antimineralocorticoid activity of single oral doses of a new aldosterone antagonist OH OPC(ME)-K was compared to that of spironolactone in two studies in healthy men. OH OPC(ME)-K reversed the urinary electrolyte response to fludrocortisone in the period up to 16 hr after treatment, but it was less potent than spironolactone on a weight basis. The best estimate of the relative potency of OH OPC(ME)-K: spironolactone (derived from a simple protocol using equal single doses of the two drugs) was 0.60:1 (95% confidence limits 0.24:1 to 1.42:1), in good agreement with the estimate from a more complex three-dose parallel-line bioassay (0.61:1, 95% confidence limits 0.48:1 to 0.79:1). The results of simple single-dose studies can be used, with certain assumptions, to provide a useful estimate of the relative potency of new aldosterone antagonists at an early stage of development.

Double-Blind Method↗