Open Access Open Access  Restricted Access Subscription Access

Are Clinically Heterogeneous Studies Synthesized in Systematic Reviews?

Johann Steurer, Sarah Scharer, Maria Wertli, Olli Miettinen


Background To assess whether in systematic reviews there occurs synthesis of the results of original studies when these studies involve prognostically dissimilar patient groups.


Methods Review of meta-analyses in systematic reviews on topics relevant to rheumatology or cardiology. In a survey panels of clinical experts assessed whether the distributions of prognostic indicators were sufficiently similar for the synthesis of results to be justified.


Results Generally, half of the experts judged the information about the prognostic indicators to be insufficient for judgment about the justifiability of the synthesis. When the panel members deemed the information to be sufficient, about half of the time they judged the synthesis to be unjustifiable due to prognostically dissimilar patient groups.


Conclusion It appears that expert consumers of the meta-analysis results from systematic reviews are quite commonly unsettled about the justifiability of those syntheses.

Full Text:



Bastian H, Glasziou P, Chalmers I: Seventy-five trials and eleven systematic reviews a day: how will we ever keep up? PLoS medicine 2010, 7(9):e1000326.

Higgins JPT, S. G: Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration 2011(Available at

Centre for Review and Dissemination: Systematic reviews: CRD's guidance for undertaking reviews in health care. In.: University of York; 2009.

Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA: The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011, 343:d5928.

Gagnier JJ, Moher D, Boon H, Beyene J, Bombardier C: Investigating clinical heterogeneity in systematic reviews: a methodologic review of guidance in the literature. BMC Med Res Methodol 2012, 12:111.

Gotzsche PC, Ioannidis JP: Content area experts as authors: helpful or harmful for systematic reviews and meta-analyses? BMJ 2012, 345:e7031.

Karppinen J, Malmivaara A, Kurunlahti M, Kyllonen E, Pienimaki T, Nieminen P, Ohinmaa A, Tervonen O, Vanharanta H: Periradicular infiltration for sciatica: a randomized controlled trial. Spine (Phila Pa 1976) 2001, 26(9):1059-1067.

Vad VB, Bhat AL, Lutz GE, Cammisa F: Transforaminal epidural steroid injections in lumbosacral radiculopathy: a prospective randomized study. Spine (Phila Pa 1976) 2002, 27(1):11-16.

Manchikanti L, Singh V, Cash KA, Pampati V, Damron KS, Boswell MV: A randomized, controlled, double-blind trial of fluoroscopic caudal epidural injections in the treatment of lumbar disc herniation and radiculitis. Spine (Phila Pa 1976) 2011, 36(23):1897-1905.

Iversen T, Solberg TK, Romner B, Wilsgaard T, Twisk J, Anke A, Nygaard O, Hasvold T, Ingebrigtsen T: Effect of caudal epidural steroid or saline injection in chronic lumbar radiculopathy: multicentre, blinded, randomised controlled trial. BMJ 2011, 343:d5278.

Foster NE, Thomas E, Barlas P, Hill JC, Young J, Mason E, Hay EM: Acupuncture as an adjunct to exercise based physiotherapy for osteoarthritis of the knee: randomised controlled trial. BMJ 2007, 335(7617):436.

Witt CM, Jena S, Selim D, Brinkhaus B, Reinhold T, Wruck K, Liecker B, Linde K, Wegscheider K, Willich SN: Pragmatic randomized trial evaluating the clinical and economic effectiveness of acupuncture for chronic low back pain. Am J Epidemiol 2006, 164(5):487-496.

Wobig M, Dickhut A, Maier R, Vetter G: Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy and safety in the osteoarthritic knee. Clin Ther 1998, 20(3):410-423.

Karlsson J, Sjogren LS, Lohmander LS: Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study. Rheumatology (Oxford) 2002, 41(11):1240-1248.

Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S et al: Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001, 358(9281):527-533.

Sabatine MS, Cannon CP, Gibson CM, Lopez-Sendon JL, Montalescot G, Theroux P, Lewis BS, Murphy SA, McCabe CH, Braunwald E: Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 2005, 294(10):1224-1232.

Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, Bode C, Burton P, Cohen M, Cook-Bruns N, Fox KA et al: Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012, 366(1):9-19.

Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, Bhatt DL, Goodman S, Verheugt FW, Flather M et al: Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011, 365(8):699-708.

Fox KA, Poole-Wilson PA, Henderson RA, Clayton TC, Chamberlain DA, Shaw TR, Wheatley DJ, Pocock SJ: Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet 2002, 360(9335):743-751.

Wallentin L, Swahn E, Kontny F, Husted S, Lagerqvist B, Stahle E: Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet 1999, 354(9180):708-715.

Dawkins KD, Grube E, Guagliumi G, Banning AP, Zmudka K, Colombo A, Thuesen L, Hauptman K, Marco J, Wijns W et al: Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for the use of drug-eluting stents in contemporary clinical practice. Circulation 2005, 112(21):3306-3313.

Dirksen MT, Vink MA, Suttorp MJ, Tijssen JG, Patterson MS, Slagboom T, Kiemeneij F, Laarman GJ: Two year follow-up after primary PCI with a paclitaxel-eluting stent versus a bare-metal stent for acute ST-elevation myocardial infarction (the PASSION trial): a follow-up study. EuroIntervention 2008, 4(1):64-70.



  • There are currently no refbacks.