Table 5.

Evidence needed in specific antibody deficiency (SAD) (24, 35).

Evidence gap	Studies required
The diagnosis of SAD is not standardized	Good quality clinical studies are needed to facilitate accurate and early identification of the deficiency and to clearly define antibody responses that are indicative of SAD
Specific evidence gaps regarding diagnosis based on response to pneumococcal vaccines Normal response to polysaccharide vaccines Specific cutoff values Effect of repeat vaccination on antibody response
Responses resulting from different sequential administration of different vaccine formulations
The prevalence of SAD is unknown, which may hinder diagnosis	Epidemiological studies are required, especially with regard to incidence in patients with specific types of infection
The natural history of SAD remains elusive	An improved understanding of the immunobiology of the disease could better inform treatment decisions
It is not known which patients will improve over time and which will have a permanent deficiency
Unclear who will benefit from IgG replacement therapy	Studies are needed to determine which patients with SAD will benefit from IgG replacement therapy, and when it should be administered
The number of cessations of IgG therapy before lifetime IgG replacement therapy is undefined
Long-term outcome of patients who improve over time is unknown	Long-term studies are required to determine the outcome for patients who improve over time
Current recommendations are based on expert opinion and there is a lack of unified guidelines	Randomized, controlled trials are needed to determine the benefit of IgG replacement therapy in patients with SAD Data from good quality clinical trials will help to form unified guidelines