The Certainty Ceiling: Why Methodological Excellence Does Not Always Lead to High-Quality Evidence

Schreijenberg M , Koes BW , Lin CC . Guideline recommendations on the pharmacological management of non-specific low back pain in primary care - is there a need to change? Expert Rev Clin Pharmacol, 2019; 12(2):145–157.

Bundesärztekammer (BÄK), Kassenärztliche Bundesvereinigung (KBV), Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF). Nationale VersorgungsLeitlinie Nicht-spezifischer Kreuzschmerz—Langfassung, 2. Auflage. Version 1. 2017. Available from: https://register.awmf.org/assets/guidelines/nvl-007l_S3_Kreuzschmerz_2017-03-abgelaufen.pdf [Last accessed: December 3, 2025].

Turk DC , Dworkin RH , Allen RR , et al. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain, 2003; 106(3):337–345.

Dworkin RH , Turk DC , Farrar JT , et al.; IMMPACT. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain, 2005; 113(1–2):9–19.

Sterne JAC , Savović J , Page MJ , et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ, 2019; 366:l4898.

Higgins JPT , Thomas J , Chandler J , Cumpston M , Li T , Page M , Welch V . (eds). Cochrane Handbook for Systematic Reviews of Interventions Version 6.5 (updated August 2024). Cochrane; 2024. Available from: www.cochrane.org/handbook. [Last accessed: December 03, 2025].

Higgins JPT , Savović J , Page MJ , Sterne JAC , RoB2 Development Group. Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Available from: https://www.cochrane.de/sites/cochrane.de/files/uploads/workshop/Lunch%20AND%20Learn/RoB_2.0_guidance_2019.pdf [Last accessed: December 3, 2025].

Hróbjartsson A , Thomsen AS , Emanuelsson F , et al. Observer bias in randomized clinical trials with measurement scale outcomes: A systematic review of trials with both blinded and nonblinded assessors. CMAJ, 2013; 185(4):E201–E211.

Guyatt GH , Oxman AD , Vist GE , et al.; GRADE Working Group. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ, 2008; 336(7650):924–926.

Guyatt GH , Oxman AD , Vist G , et al. GRADE guidelines: 4. Rating the quality of evidence–study limitations (risk of bias). J Clin Epidemiol, 2011; 64(4):407–415.

Movsisyan A , Melendez-Torres GJ , Montgomery P . Outcomes in systematic reviews of complex interventions never reached “high” GRADE ratings when compared with those of simple interventions. J Clin Epidemiol, 2016; 78:22–33.

Montgomery P , Movsisyan A , Grant SP , et al. Considerations of complexity in rating certainty of evidence in systematic reviews: A primer on using the GRADE approach in global health. BMJ Glob Health, 2019; 4(Suppl 1):e000848.