Background
Methods
Sources of evidence
Search strategy
Selection criteria
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prospective controlled studies with
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two or more arms,
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both interventional and non-interventional.
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they did not meet the aforementioned inclusion criteria,
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if they tested multi-component complementary medicine interventions,
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if they failed to report sufficient information to be included into the meta-analysis or
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where this information cannot be gleaned from authors or extracted from graphs.
Data management
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number of participants in each treatment arm
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year, when study was conducted; in case this was not given, we estimated a 3 year lag from publication date for the meta-regression
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duration of study
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country where the study was conducted
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cancer type
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age
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gender of patients
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diagnosis according to ICD 10
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duration of study
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type of study (interventional vs. non-interventional, randomized vs. non-randomized, blinded vs. not blinded, single vs. multi-center)
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additional therapy (e.g. chemotherapy)
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number of drop-outs in each study arm
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active mistletoe extract preparation (e.g. Eurixor, Iscador, etc.)
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control treatment (e.g. placebo)
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effect size of primary outcomes plus standard deviation, or confidence intervals for effect measure provided using the reported global measure of QoL
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instrument used to measure primary outcomes
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statistics according to intent-to-treat analysis (yes/no)
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sponsoring of study (corporate, public, no-sponsoring).
Risk of bias (quality) assessment
Statistical analysis
Results
Reference | Country | Study type | Participants (number at baseline; number of females; mean age) | Cancer, stage | Intervention | QoL measurement | ||
---|---|---|---|---|---|---|---|---|
verum | control | verum | control | |||||
Bar-Sela 2013 [26] | Israel | single-center, randomized, 2 arms, unblinded, interventional | 33; 5; 63 | 39; 11; 62 | lung cancer (NSCLC), IIIa, IIIb, IV | chemotherapy, Iscador Q | chemotherapy | EORTC-QLQ-C30 |
Borrelli 2001 [27] | Italya | randomized, 2 arms, unblinded, interventional | 20; 20; n/a | 10; 10; n/a | breast cancer, IV | surgery/ chemotherapy, then mistletoe extract | surgery/ chemotherapy, then water | Spitzer QoL |
Dold 1991 [28] | Germany | multi-center, randomized, 2 arms, unblinded, interventional | 114; 6; 65,6 | 113; 6; 67,5 | lung cancer (NSCLC), I-IV | conventional oncological therapy, Iscador Q | conventional oncological therapy, BVK Roche | KPI |
Enesel 2005 [29] | Romaniaa | randomized, 2 arms, unblinded, interventional | 40; n/a; n/a | 30; n/a; n/a | digestive tract cancer, n/a | surgery, Isorel A | surgery | KPI |
Grah 2010 [30] | Germany | single-center, randomized, 2 arms, unblinded, interventional | 26; 7; 64,3 | 24; 7; 63 | lung cancer (NSCLC), IIIb, IV | chemotherapy, Iscador Q spezial | chemotherapy | EORTC-QLQ-C30 |
Grossarth-Maticek, 2006a [31] | Germany | multi-center, multiple data-sets, randomized/ not randomized, 2 arms, unblinded, interventional/not interventional, nested matched pairs | MammaRand: 39; 39; 52,8 Mamma: 97; 97; 52,2 | MammaRand: 39; 39; 52,9 Mamma: 97; 97; 52,2 | breast cancer, T1a-T3 | conventional oncological therapy, Iscador | conventional oncological therapy | self-regulation |
Grossarth-Maticek, 2006b [32] | Germany | multi-center, randomized, 2 arms, unblinded, interventional, nested matched pairs | 17; 17; 44,5 | 17; 17; 44,6 | breast cancer, T2–4 | conventional oncological therapy, Iscador | conventional oncological therapy | self-regulation |
Grossarth-Maticek, 2007a [35] | Germany | multi-center, multiple data-sets, randomized/ not randomized, 2 arms, unblinded, interventional/not interventional, nested matched pairs | Cervix: 102; 102; 51 CervixMetRand: 19; 19; 47,7 | Cervix: 102; 102; 51 CervixMetRand: 19; 19; 47,6 | cervical cancer, IB-IVa | conventional oncological therapy, Iscador | conventional oncological therapy | self-regulation |
Grossarth-Maticek, 2007b [34] | Germany | multi-center, multiple data-sets, randomized/ not randomized, 2 arms, unblinded, interventional/not interventional, nested matched pairs | Ovar: 75; 75; 43 OvarRand: 21; 21; 45,4 | Ovar: 75; 75; 45,1 OvarRand: 21; 21; 45,5 | ovarian cancer, IA-C, IV | conventional oncological therapy, Iscador | conventional oncological therapy | self-regulation |
Grossarth-Maticek, 2007c [33] | Germany | multi-center, randomized, 2 arms, unblinded, interventional, nested matched pairs | 22; 8; 52 | 22; 8; 52 | melanoma, n/a | conventional oncological therapy, Iscador | conventional oncological therapy | self-regulation |
Grossarth-Maticek, 2008 [36] | Germany | multi-center, multiple data-sets, randomized/ not randomized, 2 arms, unblinded, interventional/not interventional, nested matched pairs | Corpus: 105; 105; 58,5 CorpusRand: 31; 31; 55,1 | Corpus: 105; 105; 59,1 CorpusRand: 31; 31; 55,1 | corpus uteri cancer, IA-C, IIIa-IVb | conventional oncological therapy, Iscador | conventional oncological therapy | self-regulation |
Heiny 1991 [37] | Germanya | randomized, 2 arms, unblinded, interventional | 25; 25; n/a | 21; 21; n/a | breast cancer, advanced | chemotherapy, Eurixor | chemotherapy, infusion of saline solution | QoL scale based on FLIC, self-assessment |
Heiny 1997/1998 [38] | Germanya | randomized, 2 arms, unblinded, interventional | 38; 16; 54,7 | 41; 18; 53,2 | colorectal cancer, advanced | chemotherapy, Eurixor | chemotherapy | FACT-G |
Kaiser 2001 [39] | Germanya | randomized, 2 arms, blinded, interventional, cross-over | 29; 15; n/a in both arms | 29; 15; n/a in both arms | multiple cancer, n/a | n/a, AbnobaVISCUM Mali 4 | n/a, isotone puffer | ECOG |
Kim 2012 [40] | South Korea | single-center, randomized, 2 arms, unblinded, interventional | 16; 3; 53,8 | 16; 3; 54,9 | gastric cancer, Ib, II | waiting for chemotherapy, AbnobaVISCUM Q | waiting for chemotherapy | EORTC-QLQ-C30 |
Lange O, Scholz G, Gutsch J: Modulation of the subjective and objective toxicity of an aggressive chemoradiotherapy with Helixor [Modulation der subjektiven und objektiven Toxizität einer aggressiven Chemo/Radiotherapie mit Helixor], unpublished | Germany | single-center, randomized, 2 arms, unblinded, interventional | 35; 9; 58,3 | 33; 9; 60,2 | multiple cancer, n/a | conventional oncological therapy, Helixor A | conventional oncological therapy | KPI |
Lenartz 1996 [41] | Germanya | randomized, 2 arms, unblinded, interventional | 18; 6; 52 | 17; 7; 52 | glioma, III-IV | conventional oncological therapy, mistletoe extract | conventional oncological therapy | Spitzer QoL |
Loewe-Mesch 2008 [42] | Germany | single-center, not randomized, 2 arms, unblinded, interventional | 39; 39; 47,5 | 43; 43; 47,5 | breast cancer, TIa-c, TII | chemotherapy, Iscador M spezial | chemotherapy | EORTC-QLQ-C30 |
Longhi 2014 [52] | Italy | single-center, randomized, 2 arms, unblinded, interventional | 9; 5; 28 | 11; 4; 39 | osteosarcoma, IB-IIIB | Iscador P | Etoposide (oral) | EORTC-QLQ-C30 |
Piao 2004 [44] | China | multi-center, randomized, 2 arms, unblinded, interventional | 118; 91; 52,6 | 115; 91; 51,7 | multiple cancer, pTx, pT1–4 | chemotherapy, Helixor | chemotherapy, Lentinan (i.m.) | TCM, FLIC, KPI |
Semiglasov 2004 [45] | Bulgaria, Russia, Ukraine | multi-center, randomized, 4 arms, blinded, interventional | 67; 67; 44,6 | 70; 70; 43,5 | breast cancer, pT1–3 | chemotherapy, Lektinol (PS76A) | chemotherapy, placebo | GLQ-8, Spitzer uniscale |
Semiglazov 2006 [46] | Bulgaria, Russia, Ukraine | multi-center, randomized, 2 arms, blinded, interventional | 176; 176; 46,4 | 176; 176; 45,9 | breast cancer, pTis-pT3 | chemotherapy, Lektinol (PS76A) | chemotherapy, placebo | FACT-G, GLQ-8, Spitzer uniscale |
Steuer-Vogt 2006 [47] | Germany | multi-center, randomized, 2 arms, unblinded, interventional | 200; 17; 55 | 199; 14; 55 | head neck cancer, I-IV | surgery, Eurixor | surgery | EORTC-QLQ-C30 |
Tröger 2009 [48] | Serbia | single-center, randomized, 2 arms, unblinded, interventional | 30; 30; 48,4 | 31; 31; 50,8 | breast cancer, Tx, T1–3 | chemotherapy, Iscador M spezial | chemotherapy | EORTC-QLQ-C30 |
Tröger 2014a [49] | Serbia | single-center, randomized, 2 arms, unblinded, interventional | 34; 34; 50,4 | 31; 31; 50,8 | breast cancer, Tx, T1–3 | chemotherapy, Helixor | chemotherapy | EORTC-QLQ-C30 |
Tröger 2014b [50] | Serbia | single-center, randomized, 2 arms, unblinded, interventional | 110; 45; 62,2 | 110; 47; 64,4 | pancreatic cancer, T3-T4 | supportive care, Iscador Q | supportive care | EORTC-QLQ-C30 |
Dimension | Included studies | # of patients | SMD | 95% CI | p value |
---|---|---|---|---|---|
Physical functioning | 1116 | 0,65 | −0,11-1,41 | 0,09 | |
Role functioning | 1116 | 0,63 | 0,05-1,22 | 0,04 | |
Emotional functioning | 1116 | 0,52 | −0,10 − 1,13 | 0,1 | |
Cognitive functioning | 779 | 0,46 | − 0,21 − 1,13 | 0,18 | |
Social functioning | 779 | 0,62 | 0,22-1,03 | 0,002 | |
Fatigue | 779 | −0,79 | −1,66 − 0,08 | 0,08 | |
Nausea/Vomitting | 1247 | − 0,55 | -1-(− 0,1) | 0,02 | |
Pain | 1116 | − 0,86 | − 1,54-(− 0,18) | 0,01 | |
Dyspnea | 779 | −0,37 | -0,65-(− 0,09) | 0,009 | |
Insomnia | 1247 | -0,54 | −1,23 − 0,14 | 0,12 | |
Appetite loss | 1247 | −0,62 | -1,29 − 0,05 | 0,07 | |
Constipation | 779 | − 0,14 | −0,41-0,13 | 0,31 | |
Diarrhea | 779 | -0,43 | -0,86-0,01 | 0,05 | |
Financial difficulties | 713 | -0,69 | −1,21-(− 0,16) | 0,01 |
Moderator | N studies | Effect Sizes SMDa | 95% CIs | Heterogeneity I2 | z-score | p value < =b |
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Risk of Bias status | ||||||
High | 22 | 0.66 | 0.41–0.90 | 75.5 | 5.2 | 0.001 |
Low | 1 | 0.84 | 0.62–1.1 | 0 | 7.4 | 0.001 |
Some | 7 | 0.56 | 0.12–1.0 | 93.7 | 2.5 | 0.014 |
Blinding | ||||||
Yes | 3 | 0.96 | 0.30–1.62 | 77.4 | 2.9 | 0.041 |
No | 27 | 0.61 | 0.39–0.82 | 85.3 | 5.4 | 0.001 |
Randomized | ||||||
Yes | 25 | 0.70 | 0.47–0.93 | 86.3 | 6.0 | 0.001 |
No | 5 | 0.38 | −0.09-0.85 | 63.4 | 1.58 | 0.11 |
Additional Treatment | ||||||
Chemotherapy | 7 | 0.41 | 0.05–0.76 | 89.3 | 2.2 | 0.025 |
No add. Treatment | 4 | 0.77 | 0.20–1.34 | 64.6 | 2.6 | 0.008 |
Individual best care | 1 | 2.33 | 1.93–3.38 | 0 | 5.2 | 0.001 |
Conventional | 16 | 0.58 | 0.36–0.81 | 66.2 | 5.1 | 0.001 |
Surgery | 2 | 0.62 | 0.40–0.83 | 0 | 5.5 | 0.001 |
Controls | ||||||
Active | 8 | 0.60 | 0.20–1.01 | 81.4 | 2.9 | 0.004 |
No active | 22 | 0.65 | 0.41–0.90 | 85.9 | 0.001 | |
Cancer type | ||||||
Lung cancer | 3 | −0.18 | −0.41–0.06 | 0 | 1.45 | 0.15 |
Breast cancer | 10 | 0.48 | 0.29–0.68 | 50 | 4.83 | 0.00001 |
Product | ||||||
Abnova V. | 2 | 1.06 | 0.07–2.04 | 86.5 | 2.1 | 0.036 |
Eurixor | 4 | 0.94 | 0.32–1.60 | 87.7 | 3.0 | 0.003 |
Helixor | 3 | 0.35 | 0.13–0.57 | 0 | 3.1 | 0.002 |
Iscador | 17 | 0.58 | 0.28–0.87 | 88.6 | 3.8 | 0.001 |
Lektinol | 2 | 0.67 | −0.13-1.48 | 63.4 | 1.6 | 0.1 |
Other | 2 | 0.67 | 0.26–1.09 | 0 | 3.2 | 0.001 |
Country | ||||||
Germany | 19 | 0.64 | 0.38–0.90 | 80.5 | 4.8 | 0.001 |
Other | 11 | 0.64 | 0.30–0.98 | 89.4 | 3.7 | 0.001 |
Sponsoring | ||||||
Corporate | 10 | 0.49 | 0.11–0.87 | 92.0 | 2.5 | 0.011 |
Public | 3 | 0.64 | −0.05–1.33 | 91.1 | 1.8 | 0.07 |
Mixed | 10 | 0.73 | 0.36–1.1 | 35.2 | 3.8 | 0.001 |
No Information | 7 | 0.73 | 0.27–1.19 | 82.8 | 3.1 | 0.002 |
Type of Measure | ||||||
Index1 | 6 | 0.33 | −0.12-0.78 | 50.1 | 1.4 | 0.1 |
Scale2 | 14 | 0.71 | 0.41–1.0 | 90.9 | 4.6 | 0.001 |
Self Regulation3 | 10 | 0.73 | 0.39–1.07 | 35.2 | 4.1 | 0.001 |
Moderator | Point estimate | 95% CIs | z-score | p value < = |
---|---|---|---|---|
Study Year | Model: p = 0.0001 | |||
Slope | 0.026 | 0.012–0.04 | 3.8 | 0.001 |
Age | Model: p = 0.3 | |||
Slope | −0.006 | −0.02-0.006 | −1.05 | 0.2 |
Duration of Treatment | Model: p = 0.06 | |||
Slope | 0.04 | −0.0003-0.008 | 1.8 | 0.07 |