Studii interventionalePrimele trialuri clinice randomizate efectuate in anii 1940 sub egida Medical Research Council. trialuri cu evaluarea streptomcinei in tratamentul tuberculozei (194! 1950 - Cochran si Cox publica primul tratat asupra trialurilor clinice randomizate1965 Bradford Hill & ichard !oll - Principles of medical statisticsStudii interventionaleStudii interventionaleDate obtinute de la grupuriStudiu de interventiein comunitateDate obtinute individualizatTrial clinic randomizatTrial in teren!oua ti"uri de studiu unitatea e#aluata si ex"unerea este$ 1% indi#idualizata &% o'tinuta "o"ulational(tudii inter#entionale indi#idualizate"#)rialuri clinice randomizate (terapeutice!#)rialuri in teren (trialuri de pro$ila%ie primara! subiectii sunt prote&ati printr'o masura pro$ilactica si nu vor dezvolta boala(tudii de inter#entie in comunitate ' masura educationala( pro$ilactica la nivel populational)rialul clinic randomizat *)C+)%periment stiinti$ic utilizat pentru aprecierea eficacitatii si eficientei serviciilor de sanatate #Masoara e$icacitatea terapeutica a unor proceduri terapeutice#*estarea produselor $armaceutice +mplica alocarea random (dependenta de sansa! a interventiei asupra subiectilor#Randomizarea elimina eroarea sistematica de selectie (R!+nvestigatorul realizeaza controlul e%punerii (C!)%punerea este speci$ica,locare random,locare random-nter#entie-nter#entie.ara inter#entie.ara inter#entie/fecte "oziti#e si ne0ati#e /fecte "oziti#e si ne0ati#e/santion/santion1- -12'tinerea consimtamantului informat*CRConstituirea esantionului de studiu (consimtamant in$ormat!#Criterii de includere si e%cludere#!efinitie de caz( pre$erabil cazuri noi de boala#3asuratori initiale inainte de inter#entieRandomizare,plicarea interventieiMasurarea e$ectelor( repetitiv( end'point,naliza rezultatelor*CR,#anta4e#Cea mai 'una do#ada asu"ra relatiei cauza-efect#Singurul design posibil pentru introducerea oricarei interventii medicale terapeutice#Raspuns precis la problema de sanatate evaluata!eza#anta4e#Cost" timp( resurse umane( bani#-ariere" etice( $recventa evenimentului#.oate aduce schimbari in practica medicala#Restrictia la un singur raspuns)i"uri de trialuri clinice randomizateMartori istorici 'Comparatie cu rezultate obtinute cu tratamentul conventional anterior *rial clinic $ara randomizare ' studiu simultan pentru grupul tratat si netratat dar $ara randomizare*CR ' studiu cu randomizarea subiectilor pentruinterventie/non'interventie*C $ara randomizareMartorii si subiectii tratati sunt urmariti simultanAlocarea interventiei este non-randomPopulatia --- Noua interventie ------------> EndpointPopulatia--- Martori ------------------------> Endpoint*C $ara randomizare,#anta4e#Selectia interventiei bazata pe criterii clinice#Se castiga e%perienta cu interventia noua!eza#anta4e#0imitarea comparabilitatii#Studiile pe indivizi putini nu permit detectarea di$erentelor #Selectiatratamentuluicudevierein$avoarea unor subiecti)C* "Te Standard"* Studiu in paralelNoua interventie------> EndpointPopulatia ---> !andomizarea Martori------------------> Endpoint*CR,#anta4e#(ansa e0ala la tratament/liminaeroareasistematicadeselectiein alocarea "e 0ru" tratat5netratat#Com"ara'ilitatea/0alitatea"rezenteifactorilorle0atide com"lianta si efect#6aliditatea testelor statistice3oti#e im"otri#a efectuarii )C.ilozofice/tice7o0istice+nterpretarea e$ectelor terapeutice se $ace pe baza riscului relativ( la $el+nterpretarea e$ectelor terapeutice se $ace pe baza riscului relativ( la $el ca 1n studiile de cohort2 ca 1n studiile de cohort2 dardar e%punerea este reprezentat2 de tratamente%punerea este reprezentat2 de tratament iariar RR sub valoarea de 1 semni$ic2 bene$iciu terapeutic (pentru c2RR sub valoarea de 1 semni$ic2 bene$iciu terapeutic (pentru c2 riscul evenimentului negativ la 3e%pu4i5 este riscul la cei trata6i 4i esteriscul evenimentului negativ la 3e%pu4i5 este riscul la cei trata6i 4i este mai mic dec7t la cei netrata6i!. mai mic dec7t la cei netrata6i!.iscul relati#89 iscul *decesului+ la trata:i 5iscul relati#89 iscul *decesului+ la trata:i 5 iscul *decesului+ la cei netrata:i% /x$908155iscul *decesului+ la cei netrata:i% /x$908155 08&0 9 08;5 08&0 9 08;5educerea a'solut< a riscului8 , 9netrata:i - educerea a'solut< a riscului8 , 9netrata:i -la trata:i% /x% , 9 08&0-0815 9 0805 sau 5= la trata:i% /x% , 9 08&0-0815 9 0805 sau 5=educerea riscului relati#89 1-/x%9 1-educerea riscului relati#89 1-/x%9 1- 08;5 9 08&5 sau &5= 08;5 9 08&5 sau &5=>um>) 9 15 ,unui e#eniment ne0ati#9 >>) 9 15 , #/x% >>) 9 150805 9 &0 indi#izi% !e exem"lu8 hi"oli"emiantele/x% >>) 9 150805 9 &0 indi#izi% !e exem"lu8 hi"oli"emiantele au efecte 'enefice la >>) de a"roximati# &58 adic< trat?ndau efecte 'enefice la >>) de a"roximati# &58 adic< trat?nd &5 de "ersoane se e#it< un accident coronarian ma4or%&5 de "ersoane se e#it< un accident coronarian ma4or% *rialul in teren Persoane sanatoase dar cu risc de face 'oala @ru"urile com"arate identic cu )C dar un 0ru" este "rote4at celalalt nu3asura este "rofilactica(e e#alueaza com"arati# rezultatele "oziti#e *'oala de#ine rara in 0ru"ul in care se face "rofilaxie+ si reactiile ad#erse/ficacitate #accinala/69-ne#accinati - - #accinati 5 -ne#accinati

9 1- -#accinati5-ne#accinati9 1- *-9incidenta+3exicoPanamaCosta ica6enezuelaBrazilHonduras>icara0ua!ominican e"% Colom'iaPeruChile,r0entina(outh ,frica3alaAi(in0a"oreBan0ladeshHon0 Bon0)aiAan)hailand6ietnam-ndiaBoreaBel0ium@ermanC.inlandD(,CanadaCzech e"u'lic.rance("ain-talCPri#ire de ansam'lu asu"ra studiilor clinice realizate cu #accinul ota$ date de eficacitate si si0uranta Pro0ramul 0lo'al de studii clinice #accinul ota "e 5 continente a inrolat"este E1008000 su0ari "ana la acest moment1&4 centre in 6 tari din Dniunea /uro"eana6accinul ota eficacitate8imuno0enicitate si si0uranta in /uro"a8 studiul 0F66accin rota#iral$ rezultate "ri#ind eficacitatea/ficacitatea #accinului/uro"afaza ---&*dose 106%5 CC-!50+@/6 0ra#a96=*95= C- 90-99+2rice @/6G;=*95= C- G0-9&+1Vesikari T et al. PIDJ 200423:937-432Vesikari T et al. ESPID, Basel, Switzerla! "a# 3$%, 200&, '(stra)t 7%("italizari datorate @/69F=*95= C- G&-100+("italizari datorate oricarei @/;4=*95= C- 46-G9+CC+8 9: # cell culture in$ecting dose 9:;$$u # $oci $orming units6accinuri rota#irus istoric 8ezvoltarea vaccinurilor rotavirus a inceput in anii 199F186;F cohorta e#aluata "t si0uranta >9F1855&Risc Relativ I 0%56 *0%&5 J 1%&4+KK95= C-.ara risc crescut de in#a0inatie intestinala6accinarea cu #accinul ota nu creste riscul de in#a0inatie intestinalaStudii de interventie in comunitateStudii de interventie in comunitateSimilar trialului clinic dar in conditii mai apropiate de realitateStudii interventionale in comunitati intregi=nitatea observata si analizata este grupul nu individulMazele studiului de interventie in Mazele studiului de interventie in comunitatecomunitatePo"ulatia , Po"ulatia B(e o'ser#a frec#enta factorului de risc sau a 'olii"entru o "erioada de tim",locare intam"latoare3artor -nter#entia 3asurarea efectului3asurarea efectuluiStudiul de interventie in comunitateStudiul de interventie in comunitate,#anta4e)stimeaza realistic impactul masurii!eza#anta4e.ierderea controlului speci$ic e%perimentuluiMoarte costisitor*endintele multianuale nu apar evidenteSelectia grupurilor populationaleScopul este aprecierii masurii de interventie in comunitateReprezentativitatea esantioanelor comparate este importanta pentru generalizarea rezultatelor Comunitatile trebuie alocate random la procedura pro$ilactica/terapeutica evaluate initial si urmarite identic.RandomizareaRandomizarea se aplica la nivel de comunitate nu individualScopul randomizarii este de a minimaliza e$ectul distorsionant al $actorilor de con$uzie( adica de a asigura comparabilitatea )$ecte-ndicatori monitorizati L"e "arcursM#)valuari de participare( prezentari media etc(chim'area aste"tata"#.revalenta $actorului de risc#,titudini si obiceiuri#=tilizarea serviciilor#+ncidenta boliiCommunitC -nter#ention )rial for (moNin0 Cessation *C233-)+ Proiect multicentric "entru a testa metode com'inate de control a ta'a0ismului Conce"ut "entru marii fumatori care sa fie a4utati in a'andonul si mentinerea a'andonului fumatului Conce"ut cu inter#entia media8 or0anizatii mari8 ca"a'ile sa inter#ina in comunitate in acest sco" -nce"ut in 19G9 11 "erechi de comunitati 4 ani atele de a'andon ale fumatului a"reciate in cohorte de mari fumatori selectate random 3asuri intermediare de e#aluare a acti#itatilor anti-ta'ac8 a com"ortamentului a inclus studii trans#ersale si e#aluari ale ser#iciilor medicale si nemedicale de ti" educationalOournal of the >ational Cancer -nstitute% GF*&&+$16&0-G8 1991 >o# &0%(ur0ical 3asN #s >95 es"irator for Pre#entin0 -nfluenza ,mon0 Health Care IorNers$ , andomized )rial7oe' 38 !afoe >8 3ahonC O8 et alJ'"'. C::9KD:C"1E9'195 res"irator that is fa#ored 'C the C!C or the sur0ical masN that has 'een deemed satisfactorC 'C other 0rou"s% -n #ieA of a lacN of data to document 'enefit or relati#e merit of different masN tC"es8 the -nstitute of 3edicine *-23+ con#ened a meetin0 on (e"tem'er F8 &009 and issued a re"ort entitled Respiratory Protection for Healthcare Workers in the Workplace Against Novel H1N1 Influenza A%PFQ )he conference noted that the >95 res"irators filter out 95=-99= of aerosol "articles8 'ut AorNer tolerance of these is "oorJ the su""lC is clearlC inadeRuateJ and most im"ortantlC8 there are no RualitC studies com"arin0 the relati#e merits of these & masNs for the "re#ention of influenza%3ethods% )he "artici"ants )he "ur"ose of the studC Aas to com"are the relati#e merits of sur0ical masNs and the fit-tested >95 masNs for "rotectin0 healthcare AorNers from influenza% Aere nurses AorNin0 in areas associated Aith extensi#e flu ex"osure at G hos"itals in 2ntario8 Canada% )hese "artici"ants Aere randomlC assi0ned to Aear either sur0ical masNs or fit-tested >95 masNs% elati#e merits Aere 'ased on the freRuencC of influenza demonstrated 'C "olCmerase chain reaction *PC+ or 'C serocon#ersion%esults% )he studC Aas sto""ed "rematurelC on ,"ril &F8 &009 due to the Health 3inistrCSs recommendation for sole use of the fit-tested >95 masNs% ,t that "oint8 analCsis of data collected from the 4&& nurses shoAed nearlC identical results for la'oratorC-confirmed influenza rates8 &4= in those Aearin0 sur0ical masNs8 and &F= for the >95 masNs% )he relati#e merits of sur0ical #s fit-tested >95 res"irators for "re#entin0 influenza and other res"iratorC #iruses are summarized in )a'le 4%Conclusion% )he in#esti0ators concluded that Tthe use of the sur0ical masNs com"ared Aith the >95 res"irators resulted in noninferior rates of la'oratorC-confirmed influenza%T7a'oratorC and Clinical 2utcomes(ur0ical 3asN *n 9 &1&+>95 3asN *n 9 &10+7a'oratorC-confirmed influenza 50 *&4=+ 4G *&F=+-- )-PC "ro#en 6 *F=+ 4 *&=+-- H, titer increased U 4-fold to &009 *H1>1+1; *G=+ &5 *1&=+2ther res"iratorC #iruses &0 *9=+ && *11=+-nfluenza-liNe illness 9 *4=+ & *1=+,'senteeism 4& daCs F9 daCs Pers"ecti#e% .irst8 the studC "oints out an o'#ious defect in the medical care scientific a0enda% -t is acNnoAled0ed that the masN issue is #erC im"ortant 'ecause nosocomial influenza and "rotection of the AorNforce are a #erC hi0h "rioritC8 'ut "recious feA studies "ro#ide anC data on the relati#e merits of these & #erC different masNs% >e#ertheless8 the -238 the C!C8 and the 2ccu"ational (afetC and Health ,dministration all endorsed routine use of the >95 masNs des"ite the fact that these masNs Aere su'stantiallC more ex"ensi#eJ a ma4or su""lC shorta0e Aas "redictedJ and tolerance 'C healthcare AorNers Aho had to Aear them Aas "oor% )he studC summarized a'o#e seems to demonstrate a case for sur0ical masNs8 'ut has not "ersuaded these authoritati#e sources% eason for selection% )his article Aas included 'ecause it deals Aith a rather fundamental issue in infection control -- one that is in 0reat need of a tinC slice of the 'illions s"ent on 'iomedical research%.robiotics in the criticall@ ill" , s@stematic revieO o$ the randomized trial evidenceK .etro$ )N( 8haliOal R( Manzanares L( Bohnstone B( CooP 8( Qe@land 8R Critical Care Medicine (Sep C:1C!;6N-B)C*+>)" Critical illness results in chan0es to the micro'iolo0C of the 0astrointestinal tract8 leadin0 to a loss of commensal flora and an o#er0roAth of "otentiallC "atho0enic 'acteria% ,dministerin0 certain strains of li#e 'acteria *"ro'iotics+ to criticallC ill "atients maC restore 'alance to the micro'iota and ha#e "ositi#e effects on immune function and 0astrointestinal structure and function% )he "ur"ose of this sCstematic re#ieA Aas to e#aluate the effect of "ro'iotics in criticallC ill "atients on clinical outcomes%.robiotics in the criticall@ ill" , s@stematic revieO o$ the randomized trial evidenceK .etro$ )N( 8haliOal R( Manzanares L( Bohnstone B( CooP 8( Qe@land 8R Critical Care Medicine (Sep C:1C!!/(-@>$ (Cstematic re#ieA 3/,(D/3/>)( ,>! 3,-> /(D7)($ Ie searched com"uterized data'ases8 reference lists of "ertinent articles8 and "ersonal files from 19G0 to &011% Ie included randomized controlled trials enrollin0 criticallC ill adults8 Ahich e#aluated "ro'iotics com"ared to a "lace'o and re"orted clinicallC im"ortant outcomes *infections8 mortalitC8 and len0th of staC+% , total of &F randomized controlled trials met inclusion criteria% Pro'iotics Aere associated Aith reduced infectious com"lications as documented in 11 trials *risN ratio 0%G&J 95= confidence inter#al 0%69-0%99J " 9 %0F+% Ihen data from the se#en trials re"ortin0 #entilator-associated "neumonia Aere "ooled8 #entilator-associated "neumonia rates Aere also si0nificantlC reduced Aith "ro'iotics *risN ratio 0%;5J 95= confidence inter#al 0%59-0%9;J " 9 %0F+% Pro'iotics Aere associated Aith a trend toAard reduced intensi#e care unit mortalitC *risN ratio 0%G0J 95= confidence inter#al 0%59-1%09J " 9 %16+ 'ut did not influence hos"ital mortalitC% Pro'iotics had no effect on intensi#e care unit or hos"ital len0th of staC% Com"ared to trials of hi0her methodolo0ical RualitC8 0reater treatment effects Aere o'ser#ed in trials of a loAer methodolo0ical RualitC%.robiotics in the criticall@ ill" , s@stematic revieO o$ the randomized trial evidenceK .etro$ )N( 8haliOal R( Manzanares L( Bohnstone B( CooP 8( Qe@land 8R Critical Care Medicine (Sep C:1C!C2>C7D(-2>($ Pro'iotics a""ear to reduce infectious com"lications includin0 #entilator-associated "neumonia and maC influence intensi#e care unit mortalitC% HoAe#er8 clinical and statistical hetero0eneitC and im"recise estimates "reclude stron0 clinical recommendations% .urther research on "ro'iotics in the criticallC ill is Aarranted.Medicina bazata pe doveziN abordare in $ormularea deciziei clinice prin care se cauta date din literatura medicala( se evalueaza critic rezultatele cercetarilor si apoi se alege cea mai adecvata interventie de adoptat.