Together with a co-worker, Prof Walach conducted a systematic review of mistletoe extracts (Rudolf Steiner’s anti-cancer drug) as a treatment for improving the quality of life (QoL) of cancer patients. They included all prospective controlled trials that compared mistletoe extracts with a control in cancer patients and reported QoL or related dimensions.
Walach included 26 publications with 30 data sets. The studies were heterogeneous. The pooled standardized mean difference (random effects model) for global QoL after treatment with mistletoe extracts vs. control was d = 0.61 (95% CI 0.41-0.81, p < 0,00001). The effect was stronger for younger patients, with longer treatment, in studies with lower risk of bias, in randomized and blinded studies. Sensitivity analyses supported the validity of the finding. 50% of the QoL subdomains (e.g. pain, nausea) showed a significant improvement after mistletoe treatment. Most studies had a high risk of bias or at least raise some concern.
The authors concluded that mistletoe extracts produce a significant, medium-sized effect on QoL in cancer. Risk of bias in the analyzed studies is likely due to the specific type of treatment, which is difficult to blind; yet this risk is unlikely to affect the outcome.
This is a surprising conclusion, not least because – as reported on this blog – only a year ago another German team of researchers conducted a similar review and came to a very different conclusion. Here is their abstract again:
Purpose: One important goal of any cancer therapy is to improve or maintain quality of life. In this context, mistletoe treatment is discussed to be highly controversial. The aim of this systematic review is to give an extensive overview about the current state of evidence concerning mistletoe therapy of oncologic patients regarding quality of life and side effects of cancer treatments.
Methods: In September and October 2017, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and “Science Citation Index Expanded” (Web of Science) were systematically searched.
Results: The search strategy identified 3647 articles and 28 publications with 2639 patients were finally included in this review. Mistletoe was used in bladder cancer, breast cancer, other gynecological cancers (cervical cancer, corpus uteri cancer, and ovarian cancer), colorectal cancer, other gastrointestinal cancer (gastric cancer and pancreatic cancer), glioma, head and neck cancer, lung cancer, melanoma and osteosarcoma. In nearly all studies, mistletoe was added to a conventional therapy. Regarding quality of life, 17 publications reported results. Studies with better methodological quality show less or no effects on quality of life.
Conclusions: With respect to quality of life or reduction of treatment-associated side effects, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.
How can this discrepancy be explained? Which of the reviews is drawing the correct conclusion? Here are some relevant details that could help finding an answer to these questions:
- Walach is a psychologist by training, while the senior author of the 2019 review, Jutta Huebner, is an oncologist.
- Huebner included only randomised clinical trials (RCTs), whereas Walach included any interventional and non-interventional prospective controlled study.
- Huebner included 17 RCTs that reported QoL data, while Walach included 26 publications with 30 data sets including 5 non-randomised studies.
- Several of the primary studies had been published multiple times at different stages of completion. Walach included these as independent data sets, while Huebner included each study only once.
- Huebner looked at QoL, whereas Walach also considered measurements of self-regulation as outcome measures.
- Both reviews point out that the methodological quality of the primary studies was often poor; Walach drew a positive conclusion regardless, while Huebner did not and pointed out that studies with better methodology show less or no effects on quality of life or side effects of cancer therapy.
- Walach’s review was funded by funded by the Förderverein komplementärmedizinische Forschung, Arlesheim, Switzerland, a lobby group for mistletoe therapy, while Huebner’s work was funded by the German Guideline “S3 Leitlinie Komplementärmedizin in der Behandlung von onkologischen PatientInnen (Registernummer 032-055OL)” funded by the German Cancer Aid (Fördernummer 11583) within the German Guideline Program in Oncology and by the working group Prevention and Integrative Oncology of the German Cancer Society.
I am sure there are other important differences, but the ones listed above suffice, I think, to decide which of the two papers is trustworthy and which is not.