Hepatology may have problems with putative surrogate outcome measures

Gluud, Christian; Brok, Jesper; Yang, Gong; Koretz, Ronald L.

doi:10.1016/j.jhep.2007.01.003

Cited by 133 publications

(76 citation statements)

References 71 publications

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“…8,9 Indeed, HVPG response is considered one of the best surrogate outcome measurements in hepatology. 31 As such, HVPG measurements should yield consistent and comparable results from center to center, which calls for standardization of the technique and specialist training. This has prompted the publication of several reports detailing the technical aspects of the procedure.…”

Section: Discussionmentioning

confidence: 98%

Right atrial pressure is not adequate to calculate portal pressure gradient in cirrhosis: A clinical-hemodynamic correlation study

et al. 2010

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Hepatic venous pressure gradient (HVPG), the difference between wedge and free hepatic venous pressure, is the preferred method for estimating portal pressure. However, it has been suggested that hepatic atrial pressure gradient (HAPG)-the gradient between wedge hepatic venous pressure and right atrial pressure (RAP)-might better reflect variceal hemodynamics. The aim of this study was to (1) investigate whether HAPG with nonselective beta-blockers correlates with prognosis in cirrhotic patients with portal hypertension at baseline and during treatment; (2) compare the prognostic value of HAPG with that of HVPG; and (3) investigate the agreement between portoatrial gradient (PAG) and portocaval gradient (PCG) in patients with transjugular intrahepatic portosystemic shunt (TIPS). We included 154 cirrhotic patients with varices with a complete hemodynamic study at baseline and on chronic treatment for primary (n 5 71) or secondary (n 5 83) prophylaxis for bleeding and 99 patients with TIPS. All patients were followed for up to 2 years; portal hypertensive-related bleeding and bleeding-free survival were analyzed. HVPG was equal or lower than HAPG in all patients (23.2 mm Hg; P < 0.001). Agreement between HAPG and HVPG was modest, especially in patients with increased intra-abdominal pressure. One hundred two patients were HVPG nonresponders and 52 patients were HVPG responders to nonselective beta-blockers, whereas 101 patients were HAPG nonresponders and 53 patients were HAPG responders (k 5 0.610). HVPG response revealed an excellent predictive value for bleeding risk and bleeding-free survival; HAPG did not. In our TIPS patients, 20% had a PCG 12 mm Hg and a PAG >12 mm Hg, which may have induced unnecessary overdilation of the TIPS. Conclusion: The excellent prognostic information provided by HVPG response to drug therapy is lost if HAPG response is considered. RAP should not be used for the calculation of portal pressure gradient in patients with cirrhosis.

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Section: Discussionmentioning

confidence: 98%

Right atrial pressure is not adequate to calculate portal pressure gradient in cirrhosis: A clinical-hemodynamic correlation study

et al. 2010

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“…Systematic reviews are based upon peer-reviewed protocols and folSystematic reviews are based upon peer-reviewed protocols and follow standardised methodologies. Figure 1 The hierarchy of clinical evidence of random errors (misleading results due to 'play of chance') [11][12][13][14][15][16] . We suggest possible solutions to the threats including establishment of national or transnational research infrastructures like ECRIN to improve clinical research and hereby reduce research waste [17][18][19][20][21][22][23][24][25] .…”

Section: Systematic Reviews and Meta-analysesmentioning

confidence: 99%

“…Examples of surrogate outcomes are blood cholesterol, blood glucose, sustained virological response, and blood pressure. Examples of important patient-centred outcomes are myocardial infarction, stroke, and death 16,57 . In several cases, drugs have been implemented based only on surrogate results even when similar drugs existed with proof of benefits on patient-centred outcomes 16 .…”

Section: Abuse Of Surrogate Outcomesmentioning

confidence: 99%

“…In several cases, drugs have been implemented based only on surrogate results even when similar drugs existed with proof of benefits on patient-centred outcomes 16 . Several drugs are advertised based on surrogate outcomes even though they have no effect or detrimental effects on patient-centred outcomes 13,16,29,30 . RCTs ought to assess if an intervention is safe and effective.…”

Section: Abuse Of Surrogate Outcomesmentioning

confidence: 99%

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Evidence-based clinical practice: Overview of threats to the validity of evidence and how to minimise them

Garattini

Jakobsen

Wetterslev

et al. 2016

European Journal of Internal Medicine

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103

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Abstract.Using the best quality of clinical research evidence is essential for choosing the right treatment for patients. How to identify the best research evidence is, however, difficult. In this narrative review we summarise these threats and describe how to minimise them. Pertinent literature was considered through literature searches combined with personal files. Treatments should generally not be chosen based only on evidence from observational studies or single randomised clinical trials. Systematic reviews with meta-analysis of all identifiable randomised clinical trials with Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment represent the highest level of evidence. Even though systematic reviews are trust worthier than other types of evidence, all levels of the evidence hierarchy are under threats from systematic errors (bias); design errors (abuse of surrogate outcomes, composite outcomes, etc.); and random errors (play of chance). Clinical research infrastructures may help in providing larger and better conducted trials. Trial Sequential Analysis may help in deciding when there is sufficient evidence in meta-analyses. If threats to the validity of clinical research are carefully considered and minimised, research results will be more valid and this will benefit patients and heath care systems. Sažetak. Primjena najkvalitetnijih dokaza kliničkih istraživanja ključna je u odabiru ispravnog liječenja pacijenata. No, način na koji će se odabrati najbolji dokazi predstavlja često poteškoću. Ovim preglednim člankom prikazujemo opasnosti navedenog odabira, kao i načine kako ih umanjiti. Relevantni izvori razmatrani su pretragom literature u kombinaciji s osobnim datotekama. Izbor liječenja uglavnom se ne bi smio temeljiti isključivo na opservacijskim ili pojedinačnim randomiziranim kliničkim studijama. Sustavni pregledi s metaanalizom svih identificiranih randomiziranih kliničkih studija procijenjenih sustavom stupnjevanja procjene, razvoja i evalua cije preporuka (engl. Grading of Recommendations Assessment, Development and Evaluation; GRADE) predstavljaju najvišu razinu dokaza. Iako su sustavni pregledi pouzdaniji od drugih vrsta dokaza, sve razine hijerarhije dokaza ugrožene su sustavnim pogreškama (engl. bias); pogreškama dizajna studije (zloupotreba surogatnih ishoda, složenih ishoda itd.) i slučajnim pogreškama (igra slučaja). Kliničke istraživačke infrastrukture mogu pomoći u pružanju većih i adekvatnije provedenih ispitivanja. Sekvencijska analiza studija može pomoći pri odlučivanju kada postoji dovoljna razina dokaza u metaanalizama. Ako se prijetnje valjanosti kliničkih istraživanja pažljivo razmatraju i minimiziraju, rezultati istraživanja bit će vrjedniji i korisniji pacientima i zdravstvenim sustavima.Ključne riječi: klinička praksa temeljena na dokazima; medicina temeljena na dokazima; meta-analiza; randomizirana klinička studija; sekvencijska analiza studija; sustavni pregled

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“…However, the validity of SVR as a surrogate for long-term clinical outcomes -such as decompensated liver disease, HCC and death -has been questioned. 37 It is suggested that this is because of an absence of randomised controlled trials (RCTs) in which the effects of antiviral treatment, in terms of SVR, have been correlated with long-term clinical outcomes. The exception is for cirrhotic patients in whom some evidence of a correlation between SVR and HCC has been identified (based on studies of treatment with interferon alfa monotherapy).…”

Section: Antiviral Treatmentmentioning

confidence: 99%

Peginterferon alfa and ribavirin for chronic hepatitis C in patients eligible for shortened treatment, re-treatment or in HCV/HIV co-infection: a systematic review and economic evaluation

Hartwell

Jones²,

Baxter³

et al. 2011

Health Technol Assess

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Hepatology may have problems with putative surrogate outcome measures

Cited by 133 publications

References 71 publications

Right atrial pressure is not adequate to calculate portal pressure gradient in cirrhosis: A clinical-hemodynamic correlation study

Right atrial pressure is not adequate to calculate portal pressure gradient in cirrhosis: A clinical-hemodynamic correlation study

Evidence-based clinical practice: Overview of threats to the validity of evidence and how to minimise them

Peginterferon alfa and ribavirin for chronic hepatitis C in patients eligible for shortened treatment, re-treatment or in HCV/HIV co-infection: a systematic review and economic evaluation

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