The major objective of the introductory chapter on Evidence-Based Practice and Recommendations is to show how observational and intervention studies that examined the role of nutrition in the prevention and treatment of TB, HIV and AIDS should be evaluated and used to grade the quality of evidence to form a basis for recommendations for nutrition policy and practice to help to prevent and treat these diseases. Evidence- based health policy and practices are defined, the different types of nutritional studies discussed, and guidelines (checklists) to evaluate these given with special reference to the complexities and potential pitfalls of nutrition studies.
The scientific process is characteristically divisible into two distinct cognitive processes. These are induction, during which generalisations are made from observations of particular instances (evidence) of what is being studied, and deduction, which is the process whereby a particular prediction is inferred logically from a general principle, often in the absence of direct evidence. Within the context of clinical science, basic
science and clinical observation constitute the general principles, from which deductions of predictable clinical events may sometimes be inferred.
Together with empirical and other observational clinical trials, an understanding of the basic science of nutrition and immunity may thus be useful in formulating hypotheses concerning possible therapeutic nutritional interventions that might be implemented with beneficial effect, but clinical science is increasingly aware of the need for direct evidence to support therapeutic intervention policy. The complexity of the field of nutrition is, however such that direct evidence to support generalisations is often fraught with confounding circumstances. For example, a policy to supplement diet with specific nutrients may have been based on study of a population that happened to be deficient in those nutrients, and may be entirely inappropriate for another population in which the prevalence of deficiency is different from that of the study population. An obvious population variable is life stage – for which reason this report considers adults children separately, but even within matched life stage populations, there are major heterogeneities in different geographical regions. Stemming from this is the difference between relative risk and attributable risk. In an individual with a documented, specific nutritional deficiency, say protein deficiency, the relative risk of an adverse outcome from say, tuberculosis, might be very high. On the other hand, if the prevalence of protein deficiency is low in the local population, then the risk of adverse outcome of tuberculosis attributable to protein deficiency will be proportionately lowered in that population. Clearly these issues are relevant to the development of locally or regionally appropriate policy guidelines based on scientific evidence.
For the purposes of this consensus study, the population is defined as African, and particularly, South African, and it is acknowledged that even within this narrow definition, there may be significant variation. A consequence of too narrow a definition of population is that the evidence base inevitably becomes proportionately restricted, which necessitates application of the deduction process from the basic science-generated hypothesis in many instances.
Another trap for the unwary in this field concerns the difference between evidence of association and evidence of causation. Observational studies frequently reveal associations between identifiable clinical states. These may be causally related, in which case it is not always clear which is cause and which is effect, or both states may have been caused independently by some third, unidentified factor. In resolving the exact nature of cause and effect relationships, and in thereby determining optimal therapy, there is no real substitute for the prospective, randomised controlled intervention trial, and this is particularly relevant to the field of nutrition, and even more so in the context of HIV, because nutritional deficiency and immune deficiency, whether caused by HIV infection or not, constitute a vicious cycle of mutually reinforcing abnormalities (Figure 1).
Another important consideration has been the recognition that nutrients, including essential nutrients, may be potentially harmful in excess. Three patterns of health benefit/dose response are recognised (Figure 2).
It appears unlikely that any substance, even water or oxygen, can be beneficial in unending proportionality to the administered dosage, and most essential nutrients would Figure 1. Conflating cause and effect
Immunodeficiency
Nutritional deficiency
Infections with various microorganisms constitute the major burden of disease in the developing world, which also happens to be plagued by inadequate food security and epidemics of under-nutrition. Undoubtedly there has long been evidence of association between infectious disease and nutritional deficiency states, and this is compounded by the synergies between immune deficiency and nutritional deficiency. HIV is detonating this vicious cycle on an unprecedented scale in the developing world particularly in sub-Saharan Africa.
Figure 2. Theoretical nutrient dose response curves
Linear Saturable Harmful in excess
be expected to exert a saturable response, viz. beneficial up to a certain level in correcting overt or sub clinical deficiency states, with diminishing returns thereafter. Some (such as vitamin A) may even be toxic at high doses. These are important considerations because they expose the flawed reasoning of those advocating unconsidered supplementation (of multi vitamins for example) as necessarily harmless.
Formulating policy for research and practice
It is a prime function of ASSAf to serve as an interface between scientists and policymakers. With regard to the current study, policymakers include those involved in health care delivery, and also those concerned with setting research policy. In other words, it has been the task of this panel not only to identify policy for best practice in relation to nutrition HIV/AIDS and TB, but also to define gaps in the evidence base as priority areas for further research.
One of the criticisms of a radical, purist evidence-based approach to medical decision-making and policy formulation is that professional caregivers and clinicians have expressed reservations that many years of hard-earned practical experience can potentially be discounted and undervalued in the evidence-based medicine (EBM).
Similarly, the National Department of Health might argue that they are accountable for the practical, real world (i.e. not the ivory tower) situation, and have special knowledge and skills relating to what can and cannot be done on a national level. The response of the panel to this has been to look at all the opinions, whether based on firm scientific evidence, or on clinical experience, or from the vantage point of a National Department of Health charged with the responsibility of forming and implementing policy on a national scale. The panel has looked at these 3 perspectives to identify commonalities or divergences of opinion, in the light of its own process and policy recommendations. The source material for each perspective is as follows:
Evidence-based guidelines from the consensus panel’s own studies and the 2005 1.
recommendations from the World Health Organization.
The 2006 guidelines from the Southern African HIV Clinicians Society.
2.
The 2006 guidelines from the National Department of Health.
3.