Article type
Year
Abstract
Background: Assessment of possible harm is a major part of vaccines evaluation
Objective: We report the methodological challenges of assessing evidence of possible harm following vaccination within systematic reviews.
Methods: We have conducted a series of systematic reviews assessing the evidence of possible harm of major vaccines (DTP, MMR and Hepatitis B - HB) and an adjuvant (aluminium salts), added to vaccines to stimulate immunity. All three childhood vaccines have achieved high coverage in the target populations and have been the object of safety concerns. Evidence of vaccine safety within formally conducted studies comes from two main sources: randomised evidence (RE) and observational evidence (OE). RE is useful in assessing causality of the most common and short-latency adverse events (such as fever) but is not available or inappropriate to assess rare and/or long-term events. To assess causality, studies designed to test single hypothesis (case-controls) must then be taken into consideration but their use depends on the availability of representative non-exposed controls, an increasingly rarity in the case of childhood vaccines. Available OE is presented in studies in which cases act as their own controls, either prior to exposure (before-and-after designs), or during predefined time-periods since exposure (case-crossover designs) or at different clustering times since exposure (case-base designs).
Conclusions: Issues relating to the use of RE and OE are: - Limitations and opportunities. - Difficulties in developing a classification. - Difficulties in assessing methodological quality of OE, especially case-base designs. - Difficulties in adapting review methods to include OE, especially in designs in which cases act as their own controls.
References: 1. Jefferson TO, Rudin M, Dipietrantonj C. Systematic review of the effects of DTP vaccines in children. Vaccine. 2003;21(17-18):2012-2023. 2. Demicheli V, Rivetti A, Di Pietrantonj C et al. Hepatitis B vaccination and multiple sclerosis - Evidence from a systematic review. J Viral Hepat. 2003;10(5):343-4. 3. Jefferson TO, Price D, Demicheli V, Bianco E. Unintended Events following immunisation with MMR: a systematic review. Vaccine. 2003;21(25-26):3954-60. 4. Jefferson TO, Rudin M, Dipietrantonj C. Adverse events following immunization with aluminium-containing DTP vaccines - systematic review of the evidence. Lancet Infect Dis. 2004;4: 84-90.
Objective: We report the methodological challenges of assessing evidence of possible harm following vaccination within systematic reviews.
Methods: We have conducted a series of systematic reviews assessing the evidence of possible harm of major vaccines (DTP, MMR and Hepatitis B - HB) and an adjuvant (aluminium salts), added to vaccines to stimulate immunity. All three childhood vaccines have achieved high coverage in the target populations and have been the object of safety concerns. Evidence of vaccine safety within formally conducted studies comes from two main sources: randomised evidence (RE) and observational evidence (OE). RE is useful in assessing causality of the most common and short-latency adverse events (such as fever) but is not available or inappropriate to assess rare and/or long-term events. To assess causality, studies designed to test single hypothesis (case-controls) must then be taken into consideration but their use depends on the availability of representative non-exposed controls, an increasingly rarity in the case of childhood vaccines. Available OE is presented in studies in which cases act as their own controls, either prior to exposure (before-and-after designs), or during predefined time-periods since exposure (case-crossover designs) or at different clustering times since exposure (case-base designs).
Conclusions: Issues relating to the use of RE and OE are: - Limitations and opportunities. - Difficulties in developing a classification. - Difficulties in assessing methodological quality of OE, especially case-base designs. - Difficulties in adapting review methods to include OE, especially in designs in which cases act as their own controls.
References: 1. Jefferson TO, Rudin M, Dipietrantonj C. Systematic review of the effects of DTP vaccines in children. Vaccine. 2003;21(17-18):2012-2023. 2. Demicheli V, Rivetti A, Di Pietrantonj C et al. Hepatitis B vaccination and multiple sclerosis - Evidence from a systematic review. J Viral Hepat. 2003;10(5):343-4. 3. Jefferson TO, Price D, Demicheli V, Bianco E. Unintended Events following immunisation with MMR: a systematic review. Vaccine. 2003;21(25-26):3954-60. 4. Jefferson TO, Rudin M, Dipietrantonj C. Adverse events following immunization with aluminium-containing DTP vaccines - systematic review of the evidence. Lancet Infect Dis. 2004;4: 84-90.