Randomized and double-blind studies--demands and reality as demonstrated by two examples of mistletoe research

Randomized and double-blind studies--demands and reality as demonstrated by two examples of mistletoe research.

Author information

• 
  ¹Klinik für Tumorbiologie an der Albert-Ludwigs-Universität, Breisacher Strasse 117, D-79106 Freiburg i.Br, Germany. rostock@tumorbio.uni-freiburg.de
  

Abstract

BACKGROUND:

Two examples of clinical research with mistletoe extracts were used to demonstrate essential difficulties in carrying out randomized and placebo-controlled trials. STUDY 1: In a randomized, placebo-controlled, double-blind study investigating the immunological effects of mistletoe extract, healthy subjects were asked to state whether, in their estimation, they had been treated with verum or a placebo. Due to the intrinsic effects of the mistletoe therapy--local inflammatory reactions at the injection site--100% of the subjects treated with verum and 77% of those treated with a placebo made a correct assessment of their therapy. Although double-blind trials are preferable from the methodological point of view--above all in QoL research--this study shows that double blinding is barely achievable when the investigated therapy has obvious (side) effects. STUDY 2: A prospective, randomized, multicenter study of a mistletoe therapy complementary to chemotherapy treatment of breast cancer had to be stopped after a period of 28 months, because it proved impossible to recruit more than 16 patients in six large study centers. With regard to this example and to other failed, GCP-compliant clinical trials on mistletoe therapy we describe which factors interfere with successful clinical trials. One important point, especially in the investigation of complementary cancer treatments, is that cancer patients are unwilling to have their treatment determined by randomization. Many cancer patients in Germany have their own point of view, as to whether a complementary treatment could be of benefit to them or not. Faced with a life-threatening disease they wish to determine this part of their treatment themselves.

CONCLUSION:

This background elucidates the need for improving the methodology of non-randomized trials to obtain objective and reliable results even in these fields of clinical research.

Рандомизированных двойных слепых исследований--потребности и реальности, как показал два примера омела исследования.

Два примера клинических исследований с омела экстракты использовались для демонстрации на существенные трудности в проведении рандомизированных плацебо-контролируемых испытаний. Исследование 1: рандомизированное, плацебо-контролируемое, двойное слепое исследование иммунологических эффектов омела экстракт, здоровых испытуемых просили указать, является ли, по их оценкам, они обращались с verum или плацебо. Из-за встроенных эффектов омела терапия--местные воспалительные реакции в месте инъекции--100% пациентов, лечившихся с веществом и 77% тех, кто получал плацебо правильность оценки их терапии. Хотя двойных слепых исследованиях предпочтительны с точки зрения методологической, прежде всего в КЖ исследование-это исследование показывает, что двойные слепящего едва ли достижимо, когда исследуемой терапии имеет очевидные (побочные) эффекты. Исследование 2: проспективное, рандомизированное, многоцентровое исследование омела терапия дополняет курс химиотерапии рака молочной рак пришлось прекратить после сроком на 28 месяцев, потому что это оказалось невозможно привлечь к работе более 16 пациентов в шести крупных исследовательских центров. Применительно к данному примеру и другим не удалось, GCP-совместимый клинических испытаний омела терапия мы описываем, какие факторы мешают успешные клинические испытания. Один важный момент, особенно в расследовании взаимодополняющие рак процедуры, заключается в том, что рак пациенты не желают, чтобы их лечения определяется путем рандомизации. Многие рак пациентам в Германии иметь свою собственную точку зрения относительно того, может ли дополнительное лечение может быть полезным им или нет. Столкнувшись с угрожающими жизни заболеваниями, которые они пожелают определить эту часть их лечение самостоятельно.

Вывод:

Этот фон подчеркивается необходимость совершенствования методологии нерандомизированных испытаниях для получения объективных и достоверных результатов даже в этих областях клинических исследований.

Anticancer Res. 2004 Jan-Feb;24(1):303-9.

Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial.

Piao BK¹, Wang YX, Xie GR, Mansmann U, Matthes H, Beuth J, Lin HS.

Author information

• 
  ¹Guang An Men Hospital, Beijing, China.
  

Abstract

Standardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine. A multicentric, randomized, open, prospective clinical trial was conducted in three oncological centers in the People's Republic of China in Bejing, Shenyang and Tianjin. Following the guidelines of "Good Clinical Practice" (GCP) this study was performed to get information on efficacy safety and side-effects of the standardized mistletoe extract (sME). Two hundred and thirty-three patients with breast (n=68), ovarian (n=71) and non-small cell lung cancer (NSCLC; n=94) were enrolled into this study. Two hundred and twenty-four patients fulfilled the requirements for final analysis (n=115 treated with sME HELIXOR A; n=109 comprising the control group being treated with the approved immunomodulating phytopharmacon Lentinan). All patients were provided with standard tumor-destructive treatment schedules and complementarily treated with sME or Lentinan during chemotherapy according to treatment protocol. Biometrically, the patients of the control and sME treatment group were comparable regarding distribution, clinical classification (WHO) and treatment protocols. Analysis was performed according to the "Intention to treat principle". Quality of life (QoL) was significantly (p<0.05) improved for patients who were complementarily treated with sME, as determined by the questionnaires FLIC (Functional Living Index-Cancer), TCM (Traditional Chinese Medicine Index) and the KPI (Karnofsky Performance Index) in comparison to the control group. Additionally, the occurrence of adverse events (AEs) was less frequent in the sME than in the control group (total number of AEs 52 versus 90 and number of serious AEs 5 versus 10 in study and control group, most of them due to chemotherapy). Only one serious AE was allocated to complementary treatment in each group (1 angioedema in sME group). All other side-effects of the sME (7 harmless local inflammatory reactions at subcutaneous injection site, 4 cases with fever) were self-limiting and did not demand therapeutic intervention. This study showed that complementary treatment with sME can beneficially reduce the side-effects of chemotherapy in cancer patients and thus improve quality of life.

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