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Studii interventionale

Studii interventionale. LP epidemiologie An II. Studii interventionale. Primele trialuri clinice randomizate: anii 1940 sub egida Medical Research Council. → trialuri cu evaluarea streptomcinei in tratamentul tuberculozei (1948)

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Studii interventionale

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  1. Studii interventionale LP epidemiologie An II

  2. Studii interventionale

  3. Primele trialuri clinice randomizate: anii 1940 sub egida Medical Research Council. → trialuri cu evaluarea streptomcinei in tratamentul tuberculozei (1948) • 1950 - Cochran si Cox publica primul tratat asupra trialurilor clinice randomizate • 1965 – Bradford Hill & Richard Doll - Principles of medical statistics.

  4. Interpretarea efectelor terapeutice • se face pe baza riscului relativ(ca în studiile de cohortă ) • expunerea este reprezentată de tratament RR < 1→ beneficiu terapeutic Riscul evenimentului negativ la “expuşi”: • este riscul la cei trataţi • sa fie mai mic decât la cei netrataţi

  5. Riscul relativ( RR )Reducerea absolută a riscului (RAR) 1.R= Riscul (decesului) la trataţi / Riscul (decesului) la cei netrataţi • Ex: RR = 0,15/ 0,20 = 0,75 2. Reducerea absolută a riscului (ARR absolute risk reduction) • RAR= R netrataţi - R la trataţi • Ex. RAR = 0,20-0,15 = 0,05 sau 5%

  6. Reducerea riscului relativ Număr de indivizi necesar de tratat pentru evitarea unui eveniment negativ 3.Reducerea riscului relativ, RRR = 1- RR Ex. RRR = 1- 0,75 = 0,25 sau 25% 4.Număr de indivizi necesar de tratat pentru evitarea unui eveniment negativ= NNT = 1/ RAR Ex. NNT = 1/0,05 = 20 indivizi. • NNT variaza in timp( studiu care a durat 1 an, comparativ cu 5 ani) • Nu inseamna ca evenimentele respective( fractura, stroke, IMA) sunt eliminate, doarsuntamanate • Important:duratastudiuluisicosturiletratamentului • Nu esteintotdeaunaprecizat in studiileclinice • Varianta a NNT, Number needed to vaccinate

  7. Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm( ASCOT-LLA) • studiusponsorizat de producator • beneficiileadministrarii a 10 mg de Atorvastatina   (hipolipemiant) la pacientii cu HTA( hipetensiunearteriala) sifaraboalacardiovasculara in APP( profilaxieprimara). • duratatrialului: 3,3 ani • Risculrelativ al aparitieievenimentului ( IMA) a fostredus cu 36% (relative risk reduction, RRR). RRR=36% • reducereaabsoluta a riscului =The absolute risk reduction (ARR), a fostmultmai mica (esantionul nu a avut o rata mare a BCV peduratastudiului) RR=2,67% lotulmartor , comparativ cu 1.65% la lotultratat Administrarea de Atorvastatinatimp de 3,3 ani , duce la o valoare a RAR=1,02% (2,67% minus 1,65%). • NNT=1/1,02=98,04 ,timp de 3,3 ani( numarul de indivizi care trebuietratatipentru a evita un IMA este de 98, timp de 3,3 ani).

  8. McAlister FA. The “number needed to treat” turns 20 — and continues to be used and misused. CMAJ : Canadian Medical Association Journal. 2008;179(6):549-553. doi:10.1503/cmaj.080484.

  9. NNT • reduceri la magazine in termeni de : • Reducerearisculuirelativ (RRR) ex. “economisiti 20% din pretul anterior” • Reducereaabsoluta a riscului(RAR) (ex. “economisiti 50 de lei din pretul anterior”) si nu de NNT(numbers needed to treat) “numarul de produse cu pretreduspe care trebuiesa le achizitionatipentru a abtine 1 produs gratis este….) 

  10. Douatipuri de studiu In functie de: • unitateaevaluata • expunerea 1. individualizata 2. obtinutapopulational

  11. 1.Studiile interventionaleindividualizate Dupanivelulefectului : • Trialuriclinicerandomizate (terapeutice) /nerandomizate • Trialuri in teren(trialuri de profilaxieprimara) • subiectiisuntprotejatiprintr-o masuraprofilactica • subiectii nu vordezvoltaboala.

  12. 1.Trialul clinic randomizat (TCR) Experiment stiintific : • apreciereaeficacitatiisieficienteiserviciilor de sanatate • masurareaeficacitatiiterapeuticea unorproceduriterapeutice(trial in teren) • testareaproduselorfarmaceuticeinaintede intrareapepiata

  13. Trialul clinic randomizat (TCR) • Implicaalocarearandom (dependenta de sansa) a interventieiasuprasubiectiloreliminaeroareasistematica de selectie (R) • Investigatorulcontroleazaexpunerea (C) • expunereaestespecifica

  14. TCR • Constituireaesantionului de studiu (consimtamantinformat) • Criterii de includeresiexcludere • Definitie de caz, preferabilcazurinoi de boala • Masuratoriinitiale (inainte de interventie) • Randomizare • Aplicareainterventiei • Masurareaefectului • Analizarezultatelor

  15. TCRAvantaje • Ceamaibunadovadaasuprarelatieicauza-efect • Singuruldesign posibilpentruintroducereaoricareiinterventiimedicaleterapeutice • Raspunsprecis la problema de sanatateevaluata

  16. TCRAvantaje • Sansaegala la tratament • Eliminaeroareasistematica de selectie in alocareapegruptratat/netratat • Comparabilitatea • Egalitate a prezenteifactorilorlegati de compliantasiefect • Validitateatestelorstatistice.

  17. TCRDezavantaje • Cost: timp, resurseumane, bani • Bariere: etice, frecventaevenimentului • Poateaduceschimbari in practicamedicala • Restrictia la un singurraspuns.

  18. Motive de a nu efectua TCR • Filosofice • Etice • Logistice

  19. Tipuri de trialuri clinice • Martori istorici Comparatie cu rezultate obtinute cu tratamentul conventional anterior • Trial clinic fara randomizare -studiu simultan pentru grupul tratat si netratat -fara randomizare • TCR studiu cu randomizarea subiectilor pentru interventie/non-interventie

  20. TC fara randomizare Martorii si subiectii tratati sunt urmariti simultan. Alocarea interventiei este non-random Populatia --- Noua interventie ------------> Endpoint Populatia--- Martori ------------------------> Endpoint

  21. TC fara randomizare • Avantaje • Selectiainterventieibazatapecriteriiclinice • experienta cu interventianoua • Dezavantaje • Limitareacomparabilitatii • Studiilepeindiviziputini nu permit detectareadiferentelor • Selectiatratamentului cu deviere in favoareaunorsubiecti.

  22. TCR"The Standard"* Studiu in paralel Nouainterventie------> Endpoint Populatia ---> Randomizarea Martori------------------> Endpoint

  23. TCR exempluSurgical Mask vs N95 Respirator for Preventing Influenza Among Health Care Workers: A Randomized TrialLoeb M, Dafoe N, Mahony J, et alJAMA. 2009;302:1865-1871. Epub 2009 Oct 1

  24. Surgical Mask vs N95 Respirator for Preventing Influenza Among Health Care Workers: A Randomized TrialLoeb M, Dafoe N, Mahony J, et alJAMA. 2009;302:1865-1871. Epub 2009 Oct 1 It became clear in April 2009 that a pandemic influenza with influenza A (H1N1) would occur. Although the magnitude of the pandemic was difficult to predict, it was clear that preparedness by healthcare workers was urgently needed to preserve the workforce and to prevent viral transmission to highly vulnerable patients. The major mechanism of transmission is by aerosol particles, so the major prevention method is wearing a mask, either the N95 respirator that is favored by the CDC or the surgical mask that has been deemed satisfactory by other groups.

  25. Surgical Mask vs N95 Respirator for Preventing Influenza Among Health Care Workers: A Randomized TrialLoeb M, Dafoe N, Mahony J, et alJAMA. 2009;302:1865-1871. Epub 2009 Oct 1 In view of a lack of data to document benefit or relative merit of different mask types, the Institute of Medicine (IOM) convened a meeting on September 3, 2009 and issued a report entitled Respiratory Protection for Healthcare Workers in the Workplace Against Novel H1N1 Influenza A.[3] The conference noted that the N95 respirators filter out 95%-99% of aerosol particles, but worker tolerance of these is poor; the supply is clearly inadequate; and most importantly, there are no quality studies comparing the relative merits of these 2 masks for the prevention of influenza.

  26. Methods. The purpose of the study was to compare the relative merits of surgical masks and the fit-tested N95 masks for protecting healthcare workers from influenza. The participants were nurses working in areas associated with extensive flu exposure at 8 hospitals in Ontario, Canada. These participants were randomly assigned to wear either surgical masks or fit-tested N95 masks. Relative merits were based on the frequency of influenza demonstrated by polymerase chain reaction (PCR) or by seroconversion.

  27. Results. The study was stopped prematurely on April 23, 2009 due to the Health Ministry's recommendation for sole use of the fit-tested N95 masks. At that point, analysis of data collected from the 422 nurses showed nearly identical results for laboratory-confirmed influenza rates, 24% in those wearing surgical masks, and 23% for the N95 masks. The relative merits of surgical vs fit-tested N95 respirators for preventing influenza and other respiratory viruses are summarized in Table 4.

  28. Conclusion. • The investigators concluded that "the use of the surgical masks compared with the N95 respirators resulted in noninferior rates of laboratory-confirmed influenza.” .

  29. Perspective • the study points out an obvious defect in the medical care scientific agenda. • the mask issue is very important because nosocomial influenza and protection of the workforce are a very high priority, • precious few studies provide any data on the relative merits of these 2 very different masks. Nevertheless, the IOM, the CDC, and the Occupational Safety and Health Administration all endorsed routine use of the N95 masks despite the fact that : • these masks were substantially more expensive; • a major supply shortage was predicted; • tolerance by healthcare workers who had to wear them was poor.

  30. 2.Trialul in teren(Field trial) • Persoane : • sanatoase • cu risc de face boala • Grupurile comparate identic cu TCR→ -un grup este protejat -celalalt nu • Masura este profilactica • Se evalueaza comparativ : • rezultatele pozitive (boala rara in grupul in care se face profilaxie) • reactiile adverse. • Eficacitate vaccinala EV=Inevaccinati - I vaccinati / Inevaccinati =1- Ivaccinati/Inevaccinati= 1- RR (I=incidenta)

  31. Efficacy(eficacitate)vs Effectiveness(eficienta) • Eficacitate(poateaveaefecte benefice-can it work?): masura in care o anumitaprocedura, regim, serviciudeterminaaparitiaunuiefect benefic in conditiiideale( evaluata in TCR) • Eficienta(functioneaza-does it work?):masura in care o interventiespecifica, regimsauserviciu, atuncicandsuntaplicate in conditiireale( de teren), duce la obtinerearezultatelordorite, intr-o populatiespecifica • eficienta se refera la conditiireale de utilizarevs. ideale=eficacitate

  32. The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h3740 (Published 27 July 2015)Cite this as: BMJ 2015;351:h3740

  33. 2.Studii de interventie in comunitate • masuraeducationala,profilactica.

  34. Studii de interventie in comunitate • similar trialului in teren (in conditiimaiapropiate de realitate) • studiiinterventionale in comunitatiintregi • unitateaobservatasianalizataestegrupul, nu individul.

  35. Fazele studiului de interventie in comunitate Populatia A Populatia B Se observa frecventa factorului de risc sau a bolii pentru o perioada de timp Alocare intamplatoare Interventia Martor Masurarea efectului Masurarea efectului

  36. Studiul de interventie in comunitate Avantaje • Estimeazarealistic impactulmasurii Dezavantaje • Pierdereacontrolului specific experimentului • Foartecostisitor • Tendintelemultianuale nu apar evident.

  37. Selectia grupurilor populationale • Scopul :in cemasurainterventia are efect in teren • Reprezentativitateaesantioanelorcomparateesteimportantapentrugeneralizarearezultatelor • Comunitatiletrebuie: • alocaterandom la proceduraprofilacticasauterapeutica • evaluate initial • urmariteidentic.

  38. Randomizarea • Randomizareasurvine la nivel de comunitate, nu individual • Scopulrandomizarii: • minimalizareaefectuluidistorsionant al factorilor de confuzie, • asiguracomparabilitatea.

  39. Efecte • Indicatori monitorizati “pe parcurs” • Evaluari de participare, prezentari media etc • Schimbarea asteptata: • Prevalenta factorului de risc • Atitudini si obiceiuri • Utilizarea serviciilor • Incidenta bolii

  40. North Karelia Project

  41. After the second world war cardiovascular diseases, predominantly coronary heart disease, became the leading public health problem in most of the industrialised world. Mortality statistics and other studies showed that in the 1960s the highest heart disease mortality rates were observed in Finland, predominantly in men. In the 1960s Finland led industrialized nations in heart disease mortality rates. North Karelia had Finland's highest incidence. In 1972 a long-term project was undertaken which targeted this risk in North Karelia The resulting improvement in public health is still considered remarkable, a model for the rest of the nation

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