Aşı epidemiyolojisi: Gözlemsel aşı güvenliliği çalışma tasarımları

Bir aşı programının bir toplumda uygulanmaya başlanmasından itibaren aşının etkililiğinin izlemi kadar önemli bir husus da aşı güvenliliğinin izlemidir. Her ne kadar ruhsat öncesi dönemde güvenliliği kanıtlanmış olsa da, toplumda uygulanan aşının güvenliliği ile ilgili endişeler devam edebilir. Aşı programı sürerken toplumun aşı güvenliliği ile ilgili sorularına aşı etkililiği ile ilgili sorulardan daha çabuk yanıt vermek gerekebilir. Farmakovijilans raporları ve aktif sürveyans yoluyla ortaya çıkacak bu endişelerin gözlemsel epidemiyolojik çalışma tasarımları ile giderilmesi veya doğrulanması önemlidir. Ayrıca ruhsat öncesi tespit edilmiş advers etkiler de daha doğru ve kesin bir şekilde belirlenmelidir. Bu nedenle aşı güvenliliğinin gözlemsel çalışmalarla izlenmesi aşı programlarının bir parçası olmalıdır. Geleneksel kohort ve olgu kontrol çalışmalarında yüksek aşı kapsayıcılığı nedeniyle aşısız grup bulmanın ve aşılılar ve aşısızlar arasında karşılaştırılabilirliği sağlamanın zorluğu gibi nedenlerle aşı güvenliliğinin ruhsat sonrası dönemde incelenmesi için alternatif tasarımlar geliştirilmiştir. Ancak aşılamanın uzun dönem advers etkilerinin değerlendirilmesi, kısa dönemde görülen advers etkilerinin değerlendirilmesinden daha zordur. Çünkü aşının uzun dönemdeki advers etkileri yalnızca aşılı ve aşısızların izlenerek karşılaştırılması ile belirlenebilir. Aşı güvenliliğini değerlendirmek için geleneksel gözlemsel çalışma tasarımlarına alternatif olarak kullanılan çalışma tasarımları ise daha çok kısa dönemde ortaya çıkan ve özellikle nadir advers etkilerin değerlendirilmesini sağlamaktadırlar. Bu tasarımlar; ‘risk aralığı tasarımı’, ‘kendi kendine kontrollü risk aralığı tasarımı’, ‘kendi kendine kontrollü olgu serisi tasarımı’, ‘olgu merkezli yaklaşım’, ‘olgu çaprazlama tasarımı’, ‘olgu zaman kontrol tasarımı’, ‘olgu kapsayıcılık tasarımı’, ‘ekolojik çalışmalar’ olarak sayılabilir. Aşı güvenliliği çalışmasında cevap aranan soruya ve mevcut veri kaynaklarına göre bu geleneksel ve alternatif tasarımlar arasından uygun olanın seçilmesi doğru çıkarımlar yapılabilmesi açısından gereklidir. Bu nedenle aşı güvenliliği çalışma tasarımlarının kısıtlılıkları, güçlü yönleri ve varsayımları mutlaka bilinmeli ve göz önünde bulundurulmalıdır.

Vaccine epidemiology: Observational vaccine safety study designs

After a vaccine programme introduced into a population, vaccine safety monitoring is an important issue as much as vaccine effectiveness monitoring. Concerns about vaccine safety may continue in a population after licensure, although vaccine safety was proven before licensure. While a vaccination programme implemented, it may need to respond questions about vaccine safety more quickly than questions about vaccine effectiveness. These concerns that will be revealed by pharmacovigilance reports and active surveillance should be eliminated or verified. In addition adverts events that were detected before licensure should be shown more accurately and more precisely. Therefore vaccine safety monitoring with observational studies should be a part of a vaccine programme. In traditional cohort and case-control studies finding unvaccinated groups is difficult due to high vaccine coverage and providing comparability between vaccinated and unvaccinated groups is rarely possible. Therefore alternative study designs have been developed for vaccine safety monitoring at post-licensure stage. However evaluation of long term adverse events associated with vaccines is more difficult than evaluation of short term adverse events. Long term adverse events can only be determined with studying vaccinated and unvaccinated groups over a period of time and comparing them. However alternative designs are used for investigation of short term and rare adverse events. The alternative vaccine safety study designs are ‘risk interval design’, ‘selfcontrolled risk interval design’, ‘self-controlled case series method’, ‘case-centered approach’, ‘casecrossover design’, ‘case-time-control design’, ‘casecoverage design’ and ‘ecologic studies’. According to the question sought in the vaccine safety study and available data sources, choosing the appropriate one from among these traditional and alternative designs is necessary to make correct conclusions. Therefore limitations, strenghts and assumptions of the vaccine safety study designs should be necessarily known and considered.

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