John D. Clemens

Developing improved observational methods for evaluating therapeutic effectiveness

Therapeutic efficacy is often studied with observational surveys of patients whose treatments were selected nonexperimentally. The results of these surveys are distrusted because of the fear that biased results occur in the absence of experimental principles, particularly randomization. The purpose of the current study was to develop and validate improved observational study designs by incorporating many of the design principles and patient assembly procedures of the randomized trial. The specific topic investigated was the prophylactic effectiveness of beta-blocker therapy after an acute myocardial infarction. To accomplish the research objective, three sets of data were compared. First, we developed a restricted cohort based on the eligibility criteria of the randomized clinical trial; second, we assembled an expanded cohort using the same design principles except for not restricting patient eligibility; and third, we used the data from the Beta Blocker Heart Attack Trial (BHAT), whose results served as the gold standard for comparison. In this research, the treatment difference in death rates for the restricted cohort and the BHAT trial was nearly identical. In contrast, the expanded cohort had a larger treatment difference than was observed in the BHAT trial. We also noted the important and largely neglected role that eligibility criteria may play in ensuring the validity of treatment comparisons and study outcomes. The new methodologic strategies we developed may improve the quality of observational studies and may be useful in assessing the efficacy of the many medical/surgical therapies that cannot be tested with randomized clinical trials.

User fees for health care in developing countries: A case study of Bangladesh

In designing country health care programs to achieve the goals of the Alma Alta declaration of Health for All, developing countries have been confronted with the problem of increased health care needs and decreased available resources. Health economists have proferred several possible solutions to this fiscal shortfall, including cost-recovery measures through the imposition of user fees for curative services at government health facilities. Health care providers have been noticeably absent from discussions of the many possible implications of these fees; consequently, resultant programs and policies may be economically sound but may fail to place a sufficient emphasis on features designed to maintain and improve the health of the population. In the present paper we examine the possible impact of user fees on the health of individuals residing in Bangladesh, one potential candidate country for user fees. We note evidence that the existing government health care system appears already to be providing care to two of the most medically vulnerable groups in Bangladesh, the poor and women, and provide evidence that such fees may seriously interfere with maintaining this patient profile. We discuss the significant public health role that curative care provides for the individuals, their families and the wider community. We suggest that additional questions should be asked by health care providers, anthropologists and economists prior to institution of user fees in the government system and that such measures should first be introduced in an experimental format with a rigorous and comprehensive impact evaluation.

Field trial of oral cholera vaccines in Bangladesh: evaluation of anti-bacterial and anti-toxic breast-milk immunity in response to ingestion of the vaccines

In a field trial conducted in Bangladesh, ingestion of either B subunit-killed whole cell (BS-WC) or killed whole cell (WC) oral cholera vaccines by mothers was associated with a 47% reduction of the risk of cholera in their non-vaccinated children aged under 36 months. Because vaccine-induced breast-milk immunity seemed a possible explanation for these findings, we evaluated anti-lipopolysaccharide (LPS) and anti-cholera toxin (CT) IgA antibody responses in breast milk collected during the trial from 53 lactating women who ingested three doses of BS-WC, WC, or an Escherichia coli K12 strain (K12). Despite induction of moderate vibriocidal (1.4 to 2.0-fold) and anti-CT (4.5-fold) serum antibody responses, the vaccines did not elicit significant rises of anti-LPS or anti-CT IgA breast-milk antibodies. The failure of the vaccines to elicit significant levels of breast-milk anti-cholera antibodies suggests an alternative explanation for protection of young children by maternal vaccination, such as interruption of maternal-child transmission of Vibrio cholerae 01.

11 – Cholera vaccines

The currently licensed parenteral cholera vaccine has not been a useful public health tool in the control of cholera. Building on the knowledge that primary infection offers significant protection against reinfection and that mucosal immunity mediates this protection, several oral cholera vaccines have been developed. These vaccine candidates or future candidates derived using the techniques of molecular biology will no doubt contribute to the control of cholera.

Oral B Subunit-Whole Cell Vaccine Against Cholera: From Basic Research to Successful Field Trial

Cholera is an important cause of morbidity and mortality in many devel-oping countries. Cholera is also the prototype for a large group of diarrheal diseases—the “enterotoxic enteropathies”—which may be responsible for roughly half of all diarrheal disease episodes in the world. These dis¬eases are caused by various bacteria that produce one or more toxins, which by upsetting normal fluid transport processes in the gut give rise to watery diarrhea.