Revisiones sistemáticas+/- metanálisis

Viaje al pasado

• 1981, sala de medicina interna.

• Un residente le pregunta a su tutor sobre un paciente que será egresado después de un infarto al miocardio sin complicaciones

y buen tópico para responder en el siguiente

journal club

Viaje al pasado

¿Es necesario un beta-bloqueador para que no le vuelva a dar

un infarto?

Buena pregunta

Reynolds & Whitlock. Br Heart J 1972:

“La mortalidad y la tasa de re-admisión hospitalaria no fueron diferentes entre los grupos. Esto también ocurrió con la incidencia de falla cardiaca, disnea de esfuerzo y la frecuencia de latidos ventriculares ectópicos.”

Baber et al. Br Heart J 1980: “El ensayo se diseñó para detectar un 50% de reducción en mortalidad y no se pudo demostrar tal efecto. La tasa de re-infarto fue similar en ambos grupos.”

Multicentre international study BMJ 1977: “Hasta que no surja nueva información de otros ensayos clínicos, el uso de beta-bloqueadores (hasta por dos años) es recomendado después de un infarto al miocardio no complicado.”

The Norwegian Multicentre Study Group. NEJM 1981: “Concluimos que el tratamiento a largo plazo con timolol

en pacientes que sobreviven un infarto al miocardio reduce la mortalidad y la tasa de re-infarto.”

“A pesar de aseveraciones de que reducen la frecuencia

de arritmias, sobrecarga cardiaca y tamaño del

infarto, aún no tenemos clara evidencia de que los

beta-bloqueadores mejoren la supervivencia a largo

plazo después de un infarto”

Eur Heart J

“Parece perfectamente razonable tratar con timolol

a los pacientes que sobreviven a un infarto”

Metanálsis acumulativo

Posición para dormir

Recomendaciones previas

Edición 1958

• "if [an infant] vomits, he's more likely to choke on the vomitus."

• Todos los padres y casi todos los profesionales de la salud aceptaban esto como un hecho irrefutable.

Gilbert R. et al. Int J Epidemiol. 2005;34(4):874-87

Evidencia de daño ya existía

Primeras recomendaciones en la Academia Americana de Pediatría

Gilbert R. et al. Int J Epidemiol. 2005;34(4):874-87

Textos decían...Boca abajo Lado Boca arriba

⚫⚫⚫⚫⚫ ⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫

⚫

⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫

⚫⚫⚫ ⚫⚫ ⚫⚫⚫

⚫⚫⚫⚫⚫⚫⚫⚫ ⚫⚫⚫⚫⚫⚫⚫ ⚫⚫⚫⚫

⚫ ⚫

⚫⚫ ⚫

⚫ ⚫⚫

⚫⚫⚫⚫⚫

⚫⚫⚫⚫⚫⚫

⚫⚫⚫⚫⚫⚫

⚫⚫⚫⚫

Warning

Las cosas empezaron a cambiar

De haber hecho una revisión

sistemática de la evidencia en

1970. . .

...se hubiesen prevenido 10 000 muertes de lactantes en el Reino Unido

y al menos 50 000 en Europa, EEUU y Australasia

1960

1965

1970

1975

1980

1985

1990

4 7

10

316 1783 2544

0.5 1.0 2.0

Favors Tx Favors Ctrl

1 23

2 65 3 143

11 2651 15 3311 17 3929 22 5452 23 5767

27 6125 30 6346 33 6571 43 21059 54 22051 65 47185 67 47531 67 48154

p < 0.01

p < 0.001

p < 0.0001

215

1 101 22 8

78

1 121 8 41 7 3

5 2 2 115 8 66 1

Expe

rim

enta

l

No

men

cion

ado

Rar

o / n

ada

Espe

cífic

o

Rut

ina

Terapia trombolítica para infarto al miocardio

Odds ratio

Favorece Tx Favorece Ctl

Adaptado de Antman et al. JAMA 1992

Libros de texto lo mencionaban como...

Fuga del conocimiento

Adaptado de Glasziou & Haynes, 2005

Transferencia del conocimiento

Proceso dinámico e iterativo

Incluye síntesis, diseminación,

intercambio y aplicación ética del

conocimiento

Busca mejorar la salud de la

población y proveer de productos

y servicios más efectivos

Canadian Institutes of Health Research

Investigación

Evidencia

Recomendación para la práctica clínica

Archie Cochrane, 1979

• “Una gran crítica a nuestra profesión es

que no tengamos sumarios clínicos que

aparezcan y se actualicen de manera

periódica, organizados por especialidad o

sub-especialidad, de todos los ensayos

clínicos que al momento existen.”

Se

sg

o

Recomendaciones de experto

Transversales(cross-sectional)

Observaciones clínicas(serie de casos, reporte de un

caso)

casos y controles

cohorte

Ensayo clínico aleatorio

Revisión sistemática

Analíticos

Descriptivos

Observacional

Experimental

Síntesis

Historia

Karl Pearson

Report on certain enteric fever inoculation statistics.

BMJ 1904;3:1243-6.

Historia

Revisiones sistemáticas Publicadas en Medline

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09

# d

e r

efe

ren

cia

s

Año

Revisiones sistemáticas publicadas

ECAs publicados

Y lo triste...

¿Cuáles son las diferencias?

Revisión sistemática

Revisión narrativa

vs

Revisiones narrativas

te invitan a hacer una!

¿cómo empiezo?

El editor te dice que quiere el tema: SÍNCOPE

• Hago “búsqueda” exhaustiva de la

epidemiología, fisiopatología, y demás.

• Iré a la biblioteca y al internet

Encuentro en medline mucha información!

¿CUÁL INCLUIR EN MI REVISIÓN NARRATIVA?

Encontré un artículo publicado en Chiapas, pffffffff !!

Otro de un autor de Kazakhstan...

debe ser malo; además, ni quién lo traduzca.

Otro de un autor que me cae mal

Encontré un artículo de mi compadre, Él SÍ es bueno...

Encontré más literatura! Gracias a los repres!

y las referencias siguen fluyendo...

. . . l a f l u d r o c o r t i s o n a e s e l t r a t a m i e n t o i d e a l p a r a p r e v e n c i ó n d e l s í n c o p e r e c u r r e n t e ( s e g ú n l e í e n u n l i b r o d e t e x t o ) . . .

. . . a u n q u e e n c o n t r é u n p e q u e ñ o a r t í c u l o c u y o a b s t r a c t d e c í a q u e n o s i r v e . . . n a h !

Uso gráficas para darme a entender

. . . u n a c o n c l u s i ó n , u n a m o r a l e j a f i n a l . . . y l i s t o !

IT´S FINISHED!!

I will call it Windows 7!

Característica Revisión Narrativa Revisión Sistemática

Pregunta de investigación Amplia y poco definida Clara, concreta en una situación bien definida.

Fuetes de información y revisión de la bibliografía

No especificada, no dirigida a localizar todos los estudios, alta probabilidad de sesgos

Estrategia de búsqueda sistemática y explícita de todas las fuentes y artículos relevantes

Selección de estudios Sin criterios de selección, probabilidad de sesgos

Descripción explicita de criterios de selección

Calidad de los estudios No evaluada Evaluación crítica de la calidad metodológica de los estudios.

Síntesis de datos Resumen subjetivo, generalmente cualitativo, sin un estimador estadístico.

Basada en la calidad metodológica de los estudios revisados y resumida por un estimador estadístico.

Interpretación. Basada en los estudios seleccionados y en la interpretación personal.

Basada en la evidencia científica, identificando las lagunas de conocimiento.

McAlister FA. The Medical Review Article Revisited: Has the Science Improved? Ann Intern Med. 1999;131:947-951.

Revisiones sistemáticas

• Toda investigación clínica debe iniciar y terminar en una revisión sistemática

• Te dice qué evidencia existe actualmente sobre un tema clínico

• Cualitativas:

• Cuando se presenta la evidencia en forma descriptiva, sin análisis estadístico.

• Cuantitativas o metanálisis.

• Cuando mediante el uso de técnicas estadísticas, se combinan cuantitativamente los resultados en un solo estimador puntual.

Para hacer una revisión sistemática...

• Formular pregunta clínica a revisar (PICO)

• Definir criterios de inclusión / exclusión de estudios

• Localizar estudios

• Seleccionar los estudios

• Evaluar los estudios uno por uno

• Extraer los datos de los mismos

• Analizar y presentar los resultados

Pregunta inicial

P

I ó E C

Outcome

• Es específica a una terapia, exposición o prueba diagnóstica

• Esta orientada a un problema clínico real

• Ayudará en la búsqueda de información

¿Qué tipo de estudios voy a incluir?

• Ensayos clínicos aleatorios

• Observacionales

• Idioma

• Países

• Tipo de literatura (gris, journals, tesis, abstract de congresos, autores)

• Años

randomized controlled trials comparing LP and OP in infantswith HPS have been reported. However, due to a lowfrequency in complications individual trials are frequentlyunderpowered to detect a difference in secondary outcomes(complications) between the 2 techniques. Therefore, wesought to examine the most recent publications with asystematic review and used the statistical method of meta-analysis on the best available data to compare complicationrates and outcomes of the laparoscopic and open techniquesfor pyloromyotomy, and ultimately, determine the mosteffective operative approach for this common surgicalcondition of infancy.

1. Materials and methods

1.1. Searching

A systematic review of the published literature wasperformed in February 2009. The Ovid (Ovid TechnologiesNew York, NY) and Medline search engines were used toexamine both the Pubmed and Cochrane libraries from 1966to present date. Abstracts were screened and the bibliogra-phies examined to identify any additional trials. All sourcesthat met selection criteria were analyzed. Pediatric surgeonswere queried for relevant additional studies and relevantunpublished data.

1.2. Selection criteria

All studies that compared the treatment of infants withHPS with either OP (control) or LP (experimental treatment)were considered. Only prospective studies, includingrandomized and nonrandomized designs, were selected inthis systematic review for further analysis.

1.3. Data extraction

Two reviewers (JES, HLN) used a predefined data ex-traction form to record and total all intraoperative and

postoperative complications reported in each selectedpublication. These complications included gastrointestinalperforation, serosal laceration, conversion of laparoscopic toopen procedure, incomplete pyloromyotomy, wound infec-tion, wound dehiscence, and incisional hernia. Othercomplications reported by any of the included studies werealso recorded. In addition, duration of operation, time to fullfeedings, postoperative vomiting, and postoperative lengthof stay (LOS) were recorded. Interobserver agreement washigh. Discrepancies were resolved by consensus afterdiscussion. Lastly, an overall assessment of the methodolo-gical quality of the studies was also made.

1.4. Statistical analysis

Data entry and statistical analysis was performed withReview Manager (RevMan) software Version 5.0 (Copenha-gen: The Nordic Cochrane Center, The Cochrane Collabora-tion, 2008). Comparisons of dichotomous data were carriedout using the Mantel-Haenszel statistical method underassumption of fixed effect analysis model, since includedstudies entail similar therapies. Results for comparisons ofdichotomous outcomes are expressed as odds ratio (OR) with95% confidence interval (CI). Continuous data werecompared using inverse variance statistical method withfixed effect model. The results for comparisons of contin-uous variables are expressed as mean difference (MD) with95% CI. Heterogeneity of the data was tested using a!2 statistic. Publication bias was assessed by funnelscatterplot analysis. All statistical tests were performed at5% significance level.

2. Results

2.1. Trial flow for manuscript selection

Systematic review of the literature identified 20 trials inwhich LP and OP were directly compared and potentiallyapplicable for inclusion in the meta-analysis. Of these

Table 1 Included studies LP vs OP meta-analysis

Study Design Laparoscopic Open

n Age (d) a Weight (g) a PCL (mm) a n Age (d) a Weight (g) a PCL (mm) a

Hall et al, 2009 RCT 87 34 3700 NR 93 35 3800 NRLeclair et al, 2007 RCT 50 39 3780 20.3 52 35 3790 20.1St Peter et al, 2006 RCT 100 37.3 ND 19.4 100 36.7 ND 19.5Fujimoto et al, 1999 RCT b 30 44.2 4061 25 30 43.6 3805 23Greason et al, 1997 RCT 10 34.0 4100 NR 10 31.0 4100 NRScorpio et al, 1995 PC 26 36.1 4010 NR 37 31.9 3888 NR

RCT indicates randomized controlled trial; PC, prospective cohort; PCL, pyloric channel length; ND, no difference reported; NR, not reported.a Mean values except Hall et al [6] median values reported.b Patients were alternatively assigned.

1632 J.E. Sola, H.L. Neville

Localizar los estudios

• ¿Dónde buscaré?

• Medline

• Embase

• Central

• etc...

• ¿Cómo buscaré?

• Estrategia de búsqueda (apoyo con bibliotecólogo experto)

Seleccionar lo que hallé

• Cribaje de aquellos estudios que cumplen los criterios de inclusión

• Describir porqué sí y porqué no me quedé con el estudio en cuestión

• Dibujar flujograma

randomized controlled trials comparing LP and OP in infantswith HPS have been reported. However, due to a lowfrequency in complications individual trials are frequentlyunderpowered to detect a difference in secondary outcomes(complications) between the 2 techniques. Therefore, wesought to examine the most recent publications with asystematic review and used the statistical method of meta-analysis on the best available data to compare complicationrates and outcomes of the laparoscopic and open techniquesfor pyloromyotomy, and ultimately, determine the mosteffective operative approach for this common surgicalcondition of infancy.

1. Materials and methods

1.1. Searching

A systematic review of the published literature wasperformed in February 2009. The Ovid (Ovid TechnologiesNew York, NY) and Medline search engines were used toexamine both the Pubmed and Cochrane libraries from 1966to present date. Abstracts were screened and the bibliogra-phies examined to identify any additional trials. All sourcesthat met selection criteria were analyzed. Pediatric surgeonswere queried for relevant additional studies and relevantunpublished data.

1.2. Selection criteria

All studies that compared the treatment of infants withHPS with either OP (control) or LP (experimental treatment)were considered. Only prospective studies, includingrandomized and nonrandomized designs, were selected inthis systematic review for further analysis.

1.3. Data extraction

Two reviewers (JES, HLN) used a predefined data ex-traction form to record and total all intraoperative and

postoperative complications reported in each selectedpublication. These complications included gastrointestinalperforation, serosal laceration, conversion of laparoscopic toopen procedure, incomplete pyloromyotomy, wound infec-tion, wound dehiscence, and incisional hernia. Othercomplications reported by any of the included studies werealso recorded. In addition, duration of operation, time to fullfeedings, postoperative vomiting, and postoperative lengthof stay (LOS) were recorded. Interobserver agreement washigh. Discrepancies were resolved by consensus afterdiscussion. Lastly, an overall assessment of the methodolo-gical quality of the studies was also made.

1.4. Statistical analysis

Data entry and statistical analysis was performed withReview Manager (RevMan) software Version 5.0 (Copenha-gen: The Nordic Cochrane Center, The Cochrane Collabora-tion, 2008). Comparisons of dichotomous data were carriedout using the Mantel-Haenszel statistical method underassumption of fixed effect analysis model, since includedstudies entail similar therapies. Results for comparisons ofdichotomous outcomes are expressed as odds ratio (OR) with95% confidence interval (CI). Continuous data werecompared using inverse variance statistical method withfixed effect model. The results for comparisons of contin-uous variables are expressed as mean difference (MD) with95% CI. Heterogeneity of the data was tested using a!2 statistic. Publication bias was assessed by funnelscatterplot analysis. All statistical tests were performed at5% significance level.

2. Results

2.1. Trial flow for manuscript selection

Systematic review of the literature identified 20 trials inwhich LP and OP were directly compared and potentiallyapplicable for inclusion in the meta-analysis. Of these

Table 1 Included studies LP vs OP meta-analysis

Study Design Laparoscopic Open

n Age (d) a Weight (g) a PCL (mm) a n Age (d) a Weight (g) a PCL (mm) a

Hall et al, 2009 RCT 87 34 3700 NR 93 35 3800 NRLeclair et al, 2007 RCT 50 39 3780 20.3 52 35 3790 20.1St Peter et al, 2006 RCT 100 37.3 ND 19.4 100 36.7 ND 19.5Fujimoto et al, 1999 RCT b 30 44.2 4061 25 30 43.6 3805 23Greason et al, 1997 RCT 10 34.0 4100 NR 10 31.0 4100 NRScorpio et al, 1995 PC 26 36.1 4010 NR 37 31.9 3888 NR

RCT indicates randomized controlled trial; PC, prospective cohort; PCL, pyloric channel length; ND, no difference reported; NR, not reported.a Mean values except Hall et al [6] median values reported.b Patients were alternatively assigned.

1632 J.E. Sola, H.L. Neville

of completing this document included developing a large databaseof exemplars to highlight how best to report each checklist item,and identifying a comprehensive evidence base to support theinclusion of each checklist item. The Explanation and Elaborationdocument was completed after several face to face meetings andnumerous iterations among several meeting participants, afterwhich it was shared with the whole group for additional revisionsand final approval. Finally, the group formed a disseminationsubcommittee to help disseminate and implement PRISMA.

Discussion

The quality of reporting of systematic reviews is still notoptimal [22–27]. In a recent review of 300 systematic reviews,few authors reported assessing possible publication bias [22],even though there is overwhelming evidence both for itsexistence [28] and its impact on the results of systematicreviews [29]. Even when the possibility of publication bias isassessed, there is no guarantee that systematic reviewers haveassessed or interpreted it appropriately [30]. Although theabsence of reporting such an assessment does not necessarilyindicate that it was not done, reporting an assessment of possiblepublication bias is likely to be a marker of the thoroughness ofthe conduct of the systematic review.Several approaches have been developed to conduct systematic

reviews on a broader array of questions. For example, systematic

reviews are now conducted to investigate cost-effectiveness [31],diagnostic [32] or prognostic questions [33], genetic associations[34], and policy making [35]. The general concepts and topicscovered by PRISMA are all relevant to any systematic review, notjust those whose objective is to summarize the benefits and harmsof a health care intervention. However, some modifications of thechecklist items or flow diagram will be necessary in particularcircumstances. For example, assessing the risk of bias is a keyconcept, but the items used to assess this in a diagnostic review arelikely to focus on issues such as the spectrum of patients and theverification of disease status, which differ from reviews ofinterventions. The flow diagram will also need adjustments whenreporting individual patient data meta-analysis [36].We have developed an explanatory document [18] to increase

the usefulness of PRISMA. For each checklist item, this documentcontains an example of good reporting, a rationale for its inclusion,and supporting evidence, including references, whenever possible.We believe this document will also serve as a useful resource forthose teaching systematic review methodology. We encouragejournals to include reference to the explanatory document in theirInstructions to Authors.Like any evidence-based endeavor, PRISMA is a living

document. To this end we invite readers to comment on therevised version, particularly the new checklist and flow diagram,through the PRISMA Web site. We will use such information toinform PRISMA’s continued development.

Figure 1. Flow of information through the different phases of a systematic review.doi:10.1371/journal.pmed.1000097.g001

PLoS Medicine | www.plosmedicine.org 3 July 2009 | Volume 6 | Issue 7 | e1000097

PR

ISM

A

Evaluar críticamente cada uno

• Usar la herramienta adecuada, dependiendo del tipo de estudio

• Para ECAs

• Cochrane risk of bias tool

• CASP checklist

• Escala de Jadad

• Para observacionales

• Newcastle-Ottawa

• CASP

• CEBM

potential studies, 6 (Table 1) met selection criteria [6-11] and14 were excluded [12-25] because of retrospective design.

2.2. Characteristics of included studies

Table 1 describes the characteristics of the includedstudies. The sample size of the trials ranged from 20 to 200patients per trial for a combined 625 participants forcomparison of LP (303) and OP (322). In all 6 studies,there were no statistically significant differences in age orweight of LP and OP-treated infants.

The most recent study consisted of an international,multicenter, double-blind, randomized controlled trial ofinfants treated with LP or OP [6]. In addition, 3 earlierstudies were single institution, prospective, randomizedcontrolled trials [7,8,10]. Fujimoto et al [9] reported theirstudy as a single institution, prospective, randomized trialby alternatively assigning 60 infants with pyloric stenosisto either LP or transumbilical OP. Scorpio et al [11]prospectively recorded data on 63 infants as surgeonpreference precluded randomization. Table 2 summarizesthe results of all comparisons made from the data of the6 included studies.

2.3. Complications

All 6 included studies reported intraoperative and post-operative complications. The total complication rate wassignificantly lowerwith LP (Fig. 1)with the combined estimateindicating that patients who underwent OP had an excesscomplication rate of 42% (OR, 0.58 for LP [0.35, 0.97]; P =.04). There was no evidence of statistical heterogeneity amongthe estimates (!2 = 6.06; P = .30) or publication bias.

Mucosal perforations occurred infrequently in 4 patients(1.3%) in the LP group and 3 patients (0.9%) in the OP group(OR, 1.29 [0.34, 4.86]; P = .70). All mucosal perforationswere recognized intraoperatively and repaired. Two of themucosal perforations in the LP group were repaired via anopen technique. In total, 5 (1.7%) laparoscopic procedureswere converted to open procedures. In addition to mucosalperforation, other indications for conversion includedhemodynamic instability after insufflation of the pneumo-peritoneum, severe serosal duodenal injury, and bleeding.

Two studies [6,7] reported 6 combined patients withincomplete pyloromyotomy requiring revision pyloromyo-tomy. This complication of LP approached statisticalsignificance in our analysis (OR, 7.74 [0.94, 63.38]; P = .06).

Table 2 Comparison summary of included studies LP vs OP

Comparison Studies (n) Patients (n) Effect estimate Statistical method P

Total complications 6 625 0.58 (0.35, 0.97) OR (M-H, fixed, 95% CI) .04Mucosal perforations 6 625 1.29 (0.34, 4.86) OR (M-H, fixed, 95% CI) NSIncomplete myotomy 6 625 7.74 (0.94, 63.83) OR (M-H, fixed, 95% CI) .06Wound complications 6 625 0.42 (0.20, 0.91) OR (M-H, fixed, 95% CI) .03Wound infections 6 625 0.45 (0.17, 1.19) OR (M-H, fixed, 95% CI) NSOperating time, min 6 625 0.49 (!0.94, 1.92) MD (IV, fixed, 95% CI) NSTime to full feeding, h 6 625 !11.52 (!12.77, !10.27) MD (IV, fixed, 95% CI) b.00001Postoperative emesis 5 425 0.73 (0.48, 1.11) OR (M-H, fixed, 95% CI) NSPostoperative LOS, h 5 565 !5.71 (!8.90, !2.52) MD (IV, fixed, 95% CI) .0005Gestational age, d 6 625 1.16 (!1.33, 3.65) MD (IV, fixed, 95% CI) NSWeight, g 5 425 34.65 (!98.76, 168.06) MD (IV, fixed, 95% CI) NS

OR indicates odds ratio; M-H, Mantel-Haenszel; IV, inverse variance; NS, not significant.

Fig. 1 Forest plot comparison of total complications in all included studies LP vs OP.

1633Laparoscopic vs open pyloromyotomy

Resultados - forest plot

¿Son similares los estudios?

¿Son similares los estudios?

Random vs Fixed

VS

FIXED EFFECT MODEL

“Sólo puede existir una verdad. Todos los estudios

deben tener el mismo resultado. La variabilidad entre

los mismos es debida al azar. Si todos los estudios

fueran infinitamente grandes, darían TODOS el

mismo e idéntico resultado”

“Cada estudio tiene la libertad de tener su propio resultado (su verdad). Los resultados están

distribuidos al azar alrededor de un estimación puntual. Tomaré en

cuenta los pequeños también…”

Peligro

Sesgo de publicación

Conclusiones

• La revisión de la evidencia es necesaria para los trabajadores y gestores de políticas de salud, investigadores clínicos y consumidores

• Por lo mismo, es de vital importancia que ellos puedan realizar una crítica adecuada de una revisión sistemática

• La revisión sistemática es más objetiva que las revisiones narrativas

• El meta-análisis, cuando es apropiado, es un valor agregado a la revisión sistemática.

• Revisiones sistemáticas pueden demostrar falta de evidencia adecuada y resaltar áreas de oportunidad

• Revisiones sistemáticas deben ser tan planeadas como cualquier otro trabajo de investigación

PIENSA EN GRANDEempieza poco a poco

ACTÚA AHORA

Graciaswww.cmbe.net