Омела белая Viscum album Mistletoe

3.2. Design of Studies

The oldest study (which was excluded from the analysis because of a lacking control group) dated back to 1984; all others were published in 2001 or later, the most recent being 2008. The number of patients enrolled varied considerably from 32 to 396; overall 734 patients were treated with Iscador and 741 patients served as controls. In most cases, the respective dosage of Iscador, was not given in the original studies.

The trials included in this meta-analysis were of poor quality, as indicated by randomization, matched-pair building, blinding, multicenter, description of dropouts, and so forth. (Table 1). Nine investigations reached a JADAD score of 2, five a score of 1, and one no point (Table 1). Due to methodological problems, an adequate blinding of VA-E application (which results in most cases in observable local reactions at the injection site) is not possible (reviewed in [10]), and thus the most important differentiating variable was in fact randomisation versus nonrandomisation and thus was used for the multivariable metaregression analysis.

3.3. Effect Sizes

4. Discussion

4.2. Congruence of Results

A Cochrane Review of Horneber et al. published in 2008 analyzed RCTs on various mistletoe extract preparations and indicated weak evidence that VA-E application could be effective with respect to QoL during chemotherapy for breast cancer [12]. Both groups [11, 12] argued that the main reason for the restricted informative value of the findings concerning subjective outcomes in trials with VA-E was the unblinded assessments or the unblinding of the intervention through local reactions.

Also Kienle et al. summarized in their systematic review of various RCTs from 2003 that most of these publications reported statistically significant positive outcomes (or at least positive trends) for survival or tumor remission and QoL, while several studies reported no effect on survival, recurrence, remission, and QoL [6]. In 2007, Kienle and Kiene published a systematic review of prospective clinical trials on anthroposophic mistletoe extracts and stated beneficial effects of VA-E application with respect to QoL and reduction of side effects of cytoreductive therapies in most analyzed trials [9]. They concluded that the best evidence for efficacy of VA-E exists for the improvement of QoL and the reduction of side effects of cytotoxic therapies, while the survival benefit was a matter of critique [9].

4.3. Limitations of the Used Measures of QoL and Associated Dimensions

The investigation of Kjaer, which used a less suited visual analogue scale (VAS) to measure well-being and QoL, was excluded from analysis anyway because the authors presented just the data of the VA-E arm [35, 36]. The investigation of Borelli [24] used the Spitzer Quality of Life Index [37] which covers relevant 5 QoL dimensions. Also the EORTC-QLQ C30 and BR 23 which incorporate 9 multi-item scales is among the best fitting QoL instruments [38]. The trial of Dold et al. [25] used a measure which refers to the Karnofsky performance status scale [39], which is the physician's rating of physical activity and self-supply, and rated additional medical conditions such as appetite, cough, dyspnea, pain, fever, and edema. These measures refer to important aspects of QoL and can be regarded as more or less suitable. However, this study relied on physician's rating rather than patient's self-assessment; nevertheless, to avoid a selection bias we decided to include this study too (in fact the treatment effects were rather low, and thus this decision would not promote very positive overall effects). The authors detected significant differences only with respect to subjective improvement of disorders—but there were no differences between the groups with respect to the outcomes.

All other trials used a 16-item instrument to measure psychosomatic “self-regulation” [26–33, 40], which was assumed to asses an important aspect of QoL. Recently we were able to approve correlations between “self-regulation” and QoL; this unique dimension deals with competence and autonomy of patients and thus should be regarded as an active problem-solving capacity in terms of an active adaptation to stressful situations to restore well-being [41]. Nevertheless, this dimension can be regarded as QoL associated.

4.4. Potential Bias Factors

Another intriguing fact could be that the nonrandomized studies of Grossarth-Maticek's group might have a lower external validity (generalisability), because the inclusion and exclusion criteria were not very precise and not all of them were explicitly formulated in advance. Moreover, apart from the matching criteria, there were no explicit procedures for building pairs. The most important fact was raised by the authors themselves [26, 29, 33], as they cannot exclude the possibility that patients with a good prognosis were preferentially enrolled, since patients from both groups who died shortly after the diagnosis would not have entered the study.

Because the investigations with a stronger internal validity yielded similar results as compared to the studies with the stronger external validity point in the same direction, one can conclude that the results are more or less consistent. Nevertheless, because several patients started with lower self-regulation score during the treatment, one cannot exclude the possibility of normalization and regression to the mean effects.

4.5. Explanation of Outcome Effects

One cannot ignore the fact that positive expectations of the patients are also modulating factors influencing behavior which in turn can have a strong impact on health. Expectations are also thought to underlie the so-called “placebo effects”, impacting perceptions and biological processes. In fact, invasive procedures such as injections have a higher “placebo response” compared with oral drugs [44]. One should realize that the “placebo effect” itself represents a true measurable correlate of an organism's psychoneurobiological response and, thereby, influences the healing process [45]. The “placebo effect” is taken to mean also the broad array of nonspecific effects in the patient-physician relationship, including attention, compassionate care, and the modulation of expectations; anxiety; self-awareness [46]. At least, one may suggest that all of these explanations could contribute to the observed positive effects, particularly because the application of VA-E is regarded by most patients as an active and effective chance to fight the tumor. Thus, there might be a combination of pharmacological and motivational aspects mediated by the Iscador application which may contribute to the positive outcome (Figure 5). Whatever the underlying effects are, a recent review of our group found that pooled analysis of clinical studies suggests that adjuvant treatment of cancer patients with the mistletoe extract Iscador is associated with a better survival [13], albeit we found hints for a publication bias which limits the evidence found in that meta-analysis, and this better survival is probably associated with a better QoL, too.