Non-Cochrane · intervention · PM42426686
Efficacy of Leukocyte and Platelet-Rich Fibrin (L-PRF) as an adjunct to Open Flap Debridement (OFD) in periodontal intrabony defects: a systematic review and meta-analysis.
Shahmoradi Majid, Sehat MohammadSoroush, Iranmanesh Pedram, et al. · BMC oral health · 2026 · PubMed · doi:10.1186/s12903-026-09163-z
Findings
Population Systemically healthy adults with periodontitis and intrabony defects
37 findings
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Radiographic bone fill (RBF) (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by defect morphology: 3-wall defects only | MD 1.95 [1.5, 2.39] GRADE not reported 8 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 4, one clot and two membranes | MD 0.89 [0.52, 1.26] GRADE not reported 4 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 6 months · Periodontal surgery in clinical settings | MD 1.42 [0.86, 1.98] Moderate Downgraded: inconsistency 7 studies · 288 participants |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Radiographic bone fill (RBF) (mm) 12 months · Periodontal surgery in clinical settings | MD 1.63 [1.15, 2.11] Moderate Downgraded: imprecision 3 studies · 120 participants |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by defect morphology: 2- and 3-wall defects combined | MD 1.13 [0.4, 1.87] GRADE not reported 5 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Radiographic bone fill (RBF) (mm) 9 months · Periodontal surgery in clinical settings | MD 1.73 [1.37, 2.09] Low Downgraded: inconsistency 12 studies · 614 participants |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF preparation setting: 2800 rpm for 12 min | MD 0.85 [0.4, 1.29] GRADE not reported 2 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 2, one membrane only | MD 0.93 [0.81, 1.06] GRADE not reported 2 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF preparation setting: 2800 rpm for 12 min | MD 0.72 [0.32, 1.13] GRADE not reported 2 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Gingival margin level (GML) change (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by defect morphology: 2- and 3-wall defects combined | MD 0.46 [-0.52, 1.43] GRADE not reported 2 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Gingival margin level (GML) change (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF preparation setting: 3000 rpm for 10 min | MD 0.38 [0.18, 0.58] GRADE not reported 7 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Gingival margin level (GML) change (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by defect morphology: 3-wall defects only | MD 0.44 [0.27, 0.6] GRADE not reported 7 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Radiographic bone fill (RBF) (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF preparation setting: 3000 rpm for 10 min | MD 1.94 [1.65, 2.22] GRADE not reported 10 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 2, one membrane only | MD 0.84 [0.51, 1.16] GRADE not reported 2 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by defect morphology: 3-wall defects only | MD 1.07 [0.86, 1.27] GRADE not reported 11 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 9 months · Periodontal surgery in clinical settings | MD 1.13 [0.79, 1.48] Low Downgraded: inconsistency 16 studies · 812 participants |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 1, one clot only | MD 2.02 [1.32, 2.73] GRADE not reported 4 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Radiographic bone fill (RBF) (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 2, one membrane only | MD 1.17 [0.03, 2.3] GRADE not reported 2 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Radiographic bone fill (RBF) (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by defect morphology: 2- and 3-wall defects combined | MD 1.29 [0.88, 1.69] GRADE not reported 4 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 1, one clot only | MD 1.78 [1.12, 2.44] GRADE not reported 4 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 12 months · Periodontal surgery in clinical settings | MD 2.53 [1.46, 3.61] Very low Downgraded: imprecision, inconsistency, publication bias 4 studies · 146 participants |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Gingival margin level (GML) change (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 3, one clot and one membrane | MD 0.38 [-0.02, 0.77] GRADE not reported 4 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 3, one clot and one membrane | MD 0.81 [0.47, 1.15] GRADE not reported 5 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 3, one clot and one membrane | MD 0.81 [0.42, 1.2] GRADE not reported 5 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Radiographic bone fill (RBF) (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 4, one clot and two membranes | MD 2.19 [1.96, 2.43] GRADE not reported 4 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Radiographic bone fill (RBF) (mm) 6 months · Periodontal surgery in clinical settings | MD 0.82 [0.33, 1.31] Moderate Downgraded: inconsistency 4 studies · 160 participants |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by defect morphology: 3-wall defects only | MD 1.06 [0.67, 1.44] GRADE not reported 11 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF preparation setting: 3000 rpm for 10 min | MD 1.08 [0.76, 1.41] GRADE not reported 12 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF preparation setting: 3000 rpm for 10 min | MD 1.04 [0.67, 1.41] GRADE not reported 12 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Radiographic bone fill (RBF) (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 3, one clot and one membrane | MD 1.63 [1.1, 2.16] GRADE not reported 5 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Gingival margin level (GML) change (mm) 9 months · Periodontal surgery in clinical settings | MD 0.42 [0.25, 0.59] Low Downgraded: inconsistency 9 studies · 478 participants |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 4, one clot and two membranes | MD 0.99 [0.9, 1.08] GRADE not reported 4 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 6 months · Periodontal surgery in clinical settings | MD 1.3 [0.59, 2.01] Low Downgraded: inconsistency, publication bias 7 studies · 288 participants |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 9 months · Periodontal surgery in clinical settings | MD 1.11 [0.84, 1.38] Moderate Downgraded: inconsistency 16 studies · 812 participants |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Clinical attachment level (CAL) gain (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by defect morphology: 2- and 3-wall defects combined | MD 1.33 [0.56, 2.11] GRADE not reported 5 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Gingival margin level (GML) change (mm) 9 months · Periodontal surgery in clinical settings · Subgroup by L-PRF application protocol: protocol 4, one clot and two membranes | MD 0.47 [0.23, 0.7] GRADE not reported 4 studies |
| L-PRF adjunct to open flap debridement (OFD) | OFD alone | Probing depth (PD) reduction (mm) 12 months · Periodontal surgery in clinical settings | MD 2.03 [1.49, 2.56] Low Downgraded: imprecision, inconsistency 4 studies · 146 participants |
Included primary studies 42
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Bahammam & Attia 2021 Expression of Vascular Endothelial Growth Factor Using Platelet Rich Fibrin (PRF) and Nanohydroxyapatite (nano-HA) in Treatment of… PMID:33424378 | 2021 | 3 other reviews | not stated | not extracted yet |
| Martande 2016 Platelet-Rich Fibrin Combined With 1.2% Atorvastatin for Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled… PMID:27294433 | 2016 | 3 other reviews | not stated | not extracted yet |
| Kanoriya 2016 Synergistic Approach Using Platelet-Rich Fibrin and 1% Alendronate for Intrabony Defect Treatment in Chronic Periodontitis: A Randomized… PMID:27562221 | 2016 | 2 other reviews | not stated | not extracted yet |
| Mubarak 2023 Adjunctive effect of collagen membrane coverage to L-PRF in the treatment of periodontal intrabony defects: a randomized controlled… PMID:37667213 | 2023 | 2 other reviews | not stated | not extracted yet |
| Pham 2021 INTRABONY DEFECT TREATMENT WITH PLATELET-RICH FIBRIN, GUIDED TISSUE REGENERATION AND OPEN-FLAP DEBRIDEMENT: A RANDOMIZED CONTROLLED TRIAL DOI:10.1016/j.jebdp.2021.101545 | 2021 | 2 other reviews | not stated | not extracted yet |
| Pradeep 2016 Platelet-Rich Fibrin With 1.2% Rosuvastatin for Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled Clinical… PMID:27452270 | 2016 | 2 other reviews | not stated | not extracted yet |
| Bajaj 2017 Autologous Platelet‐Rich Fibrin in the Treatment of 3‐Wall Intrabony Defects in Aggressive Periodontitis: A Randomized Controlled Clinical… DOI:10.1902/jop.2017.120661 | 2017 | 1 other review | not stated | not extracted yet |
| Bajaj 2017 Autologous Platelet-Rich Fibrin in the Treatment of 3-Wall Intrabony Defects in Aggressive Periodontitis: A Randomized Controlled Clinical… PMID:28820320 | 2017 | 1 other review | not stated | not extracted yet |
| Chatterjee 2017 Treatment of periodontal intrabony defects using autologous platelet‐rich fibrin and titanium platelet‐rich fibrin: a randomized,… DOI:10.1111/jicd.12231 | 2016 | 1 other review | not stated | not extracted yet |
| Chatterjee 2017 Treatment of periodontal intrabony defects using autologous platelet-rich fibrin and titanium platelet-rich fibrin: a randomized,… PMID:27477110 | 2017 | 1 other review | not stated | not extracted yet |
| Kanoriya 2016 Synergistic Approach Using Platelet‐Rich Fibrin and 1% Alendronate for Intrabony Defect Treatment in Chronic Periodontitis: A Randomized… DOI:10.1902/jop.2016.150698 | 2016 | 1 other review | not stated | not extracted yet |
| Kizildag 2018 The effect of leukocyte-platelet-rich fibrin on bone morphogenetic protein-2 and insulin-like growth factor-1 levels in patients with… PMID:30624092 | 2018 | 1 other review | not stated | not extracted yet |
| Martande 2016 Platelet‐Rich Fibrin Combined With 1.2% Atorvastatin for Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled… DOI:10.1902/jop.2016.150306 | 2016 | 1 other review | not stated | not extracted yet |
| Mubarak 2023 Adjunctive effect of collagen membrane coverage to L-PRF in the treatment of periodontal intrabony defects: a randomized controlled… DOI:10.1186/s12903-023-03332-0 | 2023 | 1 other review | not stated | not extracted yet |
| Pham 2021 INTRABONY DEFECT TREATMENT WITH PLATELET-RICH FIBRIN, GUIDED TISSUE REGENERATION AND OPEN-FLAP DEBRIDEMENT: A RANDOMIZED CONTROLLED TRIAL. PMID:34479673 | 2021 | 1 other review | not stated | not extracted yet |
| Pradeep 2012 Comparative Evaluation of Autologous Platelet‐Rich Fibrin and Platelet‐Rich Plasma in the Treatment of 3‐Wall Intrabony Defects in Chronic… DOI:10.1902/jop.2012.110705 | 2012 | 1 other review | not stated | not extracted yet |
| Pradeep 2012 Comparative evaluation of autologous platelet-rich fibrin and platelet-rich plasma in the treatment of 3-wall intrabony defects in chronic… PMID:22348695 | 2012 | 1 other review | not stated | not extracted yet |
| Pradeep 2015 Platelet-rich fibrin with 1% metformin for the treatment of intrabony defects in chronic periodontitis: a randomized controlled clinical… PMID:25762357 | 2015 | 1 other review | not stated | not extracted yet |
| Pradeep 2017 Platelet-Rich Fibrin Combined With a Porous Hydroxyapatite Graft for the Treatment of 3-Wall Intrabony Defects in Chronic Periodontitis: A… PMID:29314065 | 2017 | 1 other review | not stated | not extracted yet |
| Thorat 2017 Adjunctive Effect of Autologous Platelet-Rich Fibrin in the Treatment of Intrabony Defects in Localized Aggressive Periodontitis Patients:… DOI:10.11607/prd.2972 | 2017 | 1 other review | not stated | not extracted yet |
| Thorat 2017 Adjunctive Effect of Autologous Platelet-Rich Fibrin in the Treatment of Intrabony Defects in Localized Aggressive Periodontitis Patients:… PMID:29023611 | 2017 | 1 other review | not stated | not extracted yet |
| Ajwani 2015 Comparative evaluation of autologous platelet-rich fibrin versus platelet-rich fibrin combined with demineralized freeze-dried bone… DOI:10.4103/jioh.jioh_80_21 | 2022 | this review only | not stated | not extracted yet |
| Ajwani 2015 Comparative evaluation of platelet-rich fibrin biomaterial and open flap debridement in the treatment of two and three wall intrabony… PMID:25954068 | 2015 | this review only | not stated | not extracted yet |
| Arabaci 2017 Advantages of Autologous Platelet‐Rich Fibrin Membrane on Gingival Crevicular Fluid Growth Factor Levels and Periodontal Healing: A… DOI:10.1902/jop.2017.160485 | 2017 | this review only | not stated | not extracted yet |
| Arabaci 2017 Advantages of Autologous Platelet-Rich Fibrin Membrane on Gingival Crevicular Fluid Growth Factor Levels and Periodontal Healing: A… PMID:28452623 | 2017 | this review only | not stated | not extracted yet |
| Bahammam 2021 Expression of Vascular Endothelial Growth Factor Using Platelet Rich Fibrin (PRF) and Nanohydroxyapatite (nano-HA) in Treatment of… DOI:10.1016/j.sjbs.2020.11.027 | 2021 | this review only | not stated | not extracted yet |
| Chandradas 2016 Efficacy of platelet rich fibrin in the treatment of human intrabony defects with or without bone graft: A randomized controlled trial. PMID:27652249 | 2016 | this review only | not stated | not extracted yet |
| Kizildag 2018 The effect of leukocyte-platelet-rich fibrin on bone morphogenetic protein-2 and insulin-like growth factor-1 levels in patients with… DOI:10.1080/08977194.2018.1551217 | 2018 | this review only | not stated | not extracted yet |
| Patel 2017 Platelet‐Rich Fibrin in Regeneration of Intrabony Defects: A Randomized Controlled Trial DOI:10.1902/jop.2017.130710 | 2017 | this review only | not stated | not extracted yet |
| Patel 2017 Platelet-Rich Fibrin in Regeneration of Intrabony Defects: A Randomized Controlled Trial. PMID:28820322 | 2017 | this review only | not stated | not extracted yet |
| Pendyala 2025 Contingent Analysis of Open Flap Debridement, Leukocyte-Rich Platelet-Rich Fibrin and Titanium Platelet-Rich Fibrin in the Treatment of… DOI:10.4103/jicdro.jicdro_91_24 | 2025 | this review only | not stated | not extracted yet |
| Pradeep 2015 Platelet‐Rich Fibrin With 1% Metformin for the Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled Clinical… DOI:10.1902/jop.2015.140646 | 2015 | this review only | not stated | not extracted yet |
| Pradeep 2016 Platelet‐Rich Fibrin With 1.2% Rosuvastatin for Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled Clinical… DOI:10.1902/jop.2016.160015 | 2016 | this review only | not stated | not extracted yet |
| Pradeep 2017 Platelet‐Rich Fibrin Combined With a Porous Hydroxyapatite Graft for the Treatment of 3‐Wall Intrabony Defects in Chronic Periodontitis: A… DOI:10.1902/jop.2012.110722 | 2017 | this review only | not stated | not extracted yet |
| Razi 2021 Effectiveness of Platelet-Rich Fibrin in the Treatment of Intrabony Defects with or Without Bone Graft: A Clinical Comparative Study. PMID:35017987 | 2021 | this review only | not stated | not extracted yet |
| Rosamma 2012 Clinical effectiveness of autologous platelet rich fibrin in the management of infrabony periodontal defects DOI:10.1016/j.sdj.2012.10.003 | 2012 | this review only | not stated | not extracted yet |
| Rosamma 2012 Clinical effectiveness of autologous platelet rich fibrin in the management of infrabony periodontal defects. PMID:23739317 | 2012 | this review only | not stated | not extracted yet |
| Sharma & Pradeep 2011 Treatment of 3-wall intrabony defects in patients with chronic periodontitis with autologous platelet-rich fibrin: a randomized controlled… PMID:21513477 | 2011 | this review only | not stated | not extracted yet |
| Sharma 2011 Treatment of 3‐Wall Intrabony Defects in Patients With Chronic Periodontitis With Autologous Platelet‐Rich Fibrin: A Randomized Controlled… DOI:10.1902/jop.2011.110075 | 2011 | this review only | not stated | not extracted yet |
| Thorat 2011 Clinical effect of autologous platelet-rich fibrin in the treatment of intra-bony defects: a controlled clinical trial DOI:10.1111/j.1600-051x.2011.01760.x | 2011 | this review only | not stated | not extracted yet |
| Thorat 2011 Clinical effect of autologous platelet-rich fibrin in the treatment of intra-bony defects: a controlled clinical trial. PMID:21777267 | 2011 | this review only | not stated | not extracted yet |
| Yajamanya 2017 Bioactive glass versus autologous platelet-rich fibrin for treating periodontal intrabony defects: A comparative clinical study. PMID:29386798 | 2017 | this review only | not stated | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Systemically healthy adults (18 years or older) with periodontitis and at least one periodontal intrabony defect; smokers, pregnant or lactating women and systemic disease excluded | Periodontal intrabony defects in systemically healthy non-smoking adults; 2- and/or 3-wall (n=10) and 3-wall only (n=13) |
| Intervention | OFD combined with adjunctive L-PRF (standard L-PRF only; other platelet concentrates and L-PRF combined with other biomaterials excluded) | OFD plus L-PRF (centrifugation 3000 rpm for 10 min in 15 trials; other settings in the rest) |
| Comparison | OFD alone | OFD alone |
| Outcomes | Primary: probing depth and clinical attachment level change; secondary: radiographic bone fill and gingival margin level change | PD (n=16 at 9 months), CAL (n=16 at 9 months), RBF (n=12 at 9 months), GML (n=9 at 9 months) |
| Study designs | RCTs (parallel-group and split-mouth) | 23 RCTs (15 parallel-group, 8 split-mouth); India 18, Turkey 2, Egypt 1, Vietnam 1, Saudi Arabia 1 |
| Timing | Minimum follow-up 6 months | 6, 9 and 12 months |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | Yes | Yes | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes | RCT: Yes | yes |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: No | RCT: No | yes |
| 12Impact of risk of bias on the pooled results | Yes | Yes | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | Yes | Yes | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Low | Low | yes |