Tom Jefferson

The effectiveness and safety of vaccines against human anthrax: a systematic review

We report on the results of a systematic review of existing controlled clinical trials undertaken to assess the effectiveness and safety of vaccines against human anthrax in relation to disease incidence and side-effects. Two articles retrieved by electronic and hand search fulfilling some of the inclusion criteria underwent a quality assessment by a group of reviewers. Data synthesized from the two trials showed that estimates of overall effectiveness and safety favour treatment (overall odds ratio 0.16; 95% confidence interval 0.07-0.34). The route of inoculation appears to make little difference to the effectiveness of the vaccines; however, one study shows that the incidence and severity of side-effects are significantly higher with the killed vaccine than with the alum-based placebo (overall odds ratio 0.16; 95% confidence interval 2.38-27.17).

An exercise on the feasibility of carrying out secondary economic analyses

Purchasers of health services need up to date information on cost-effectiveness of interventions to help in prioritising spending. But economists have not yet developed a formal methodology for reviewing and summing up evidence from individual economic evaluations which may have been conducted at different times and in different places, or indeed for assessing whether such systematic reviews are possible in this context. This paper discusses the problems of reviewing available economic information, using a body of literature on the economics of influenza vaccination to illustrate some relevant issues. First, the paper examines alternative methods for adjusting prices to take into account differences in currency and time periods: Retail Price Indices are compared with health specific inflation indices, and exchange rates are compared with Purchasing Power Parity (PPP) data. For the studies reviewed, the choice of conversion method made little practical difference. Secondly, the paper explores the possibility of summarising the results of a review in terms of quantities of resources used, rather than prices. This method is constrained by the available data, but could be more generally useful as it allows direct comparison of underlying technologies, and calculation of costs by attaching local unit costs to the resources associated with an intervention. These two exercises highlight many of the problems that arise in generalising from economic studies. Both methods need to be developed further if they are to be useful to decision makers.

The quest for trials on the efficacy of human vaccines. Results of the handsearch of Vaccine

We report the results of the handsearch of all the issues of Vaccine from 1983 to 1994 to identify randomized and controlled clinical trials (RCTs and CCTs) with the aim of setting up a Cochrane data base of vaccine trials. We read 1119 original papers and located 231 trials of which 117 (50.6%) were RCTs and 114 (49.4%) were CCTs. This compared with a MEDLINE search yield of only 60 trials (25.9% of reports identified by handsearching). Hepatitis B vaccine was the most popular topic (25.5% of trial reports), followed by influenza (13.4% of trial reports) and Hepatitis A (10.4% of trial reports). Seventy per cent of trials had been carried out in Europe or North America and mean overall trial size was 1136 patients (median 110). Overall only 20 trial reports mentioned placebo explicitly, while 22 reports contained data on both overall and arm size which could not be reconciled. Reviewers of vaccine trials should not base searches exclusively on MEDLINE as they are likely to miss up to 75% of trial reports. Vaccine should adopt a standardized format of reporting of trials and contributors should conform to these rules.

Methodological quality of economic modelling studies. A case study with hepatitis B vaccines.

The notable increase in the quantity of economic evaluations in the last 2 decades has not been matched by good methodological standards. This problem is particularly evident in the field of economic evaluations of hepatitis B vaccines. The results of 2 systematic reviews conducted by us in 1993 and 1996 showed three problem areas. A sizeable minority of study reports failed to provide a clear study aim, showing a basic ignorance of the first rule of conducting scientific research. The basic epidemiological assumptions upon which the economic models were based showed variability which persisted even after stratification, raising the question of the accuracy of the epidemiological knowledge base of hepatitis B infection and its progression. Lastly, many of the studies showed weaknesses in basic methods of conducting and reporting economic evaluations.Examination of these problem areas led us to conclude that no conclusions about the efficiency of hepatitis B vaccines could be drawn from the available evidence. Addressing the problem of poor methodological standards concerns the whole research community. However, as a proportion of economic evaluations are published, one obvious means of exerting pressure to increase and maintain methodological standards is the editorial and peer review process. Editors of specialist and general medical journals should agree on and enforce common explicit guidelines for study conduct and reporting, following the example of the British Medical Journal.

Economic aspects of a small epidemic of hepatitis A in a religious community in Northern Italy

We report on a small (11 cases) outbreak of hepatitis A (HA) which occurred in the village of Narzole in the province of Cuneo, Northern Italy. Cases were reported during the period December 1993-March 1994 and centred around a Christian community centre caring for broken homes. Eight cases were children aged 7-13 and three were adults. The incidence for all ages was 354.8 per 100,000 inhabitants. Due to local resistance to the investigation of the outbreak we were unable to identify the source of the outbreak. Marginal and average costs were identified during the outbreak using a proforma and include costs of the investigation. The mean costs per case were

Redundant publication in biomedical sciences: scientific misconduct or necessity?

7899 (average) and

Are guidelines for peer‐reviewing economic evaluations necessary? A survey of current editorial practice

1793 (marginal). The main cost generators were costs of care if average costs only are considered (81% of total costs) or loss of productivity if only marginal costs are calculated (60% of total marginal costs). Small epidemics such as the one described appear to use a considerable amount of health care and personal resources. However, when marginal and opportunity considerations are applied (value of opportunities foregone for alternative use of resources), such costs decrease. This is especially valid for all treatment costs, as the majority of hospital running costs are fixed. The small number of cases and the high hospitalization rate (100%) make the epidemic of uncertain extrapolation.