Müller-Vahl Kirsten R, Jakubovski Ewgeni, Fremer Carolin, Lenz-Ziegenbein Martina, Großhennig Anika, Klages Carolin, Koch Armin, Haas Martina, Pisarenko Anna
Clinic of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
Institute for Biostatistics, Hannover Medical School, Hannover, Germany.
Front Neurosci. 2022 Sep 21;16:793703. doi: 10.3389/fnins.2022.793703. eCollection 2022.
Randomized double-blind placebo-controlled trials (RCTs) are regarded as the gold standard for clinical trials. While there are established standards to avoid unblinding, in RCTs using tetrahydrocannabinol (THC) containing cannabinoids, however, accidental unblinding and intentional self-unbinding must be considered as a particular issue, since THC tests are widely available. To investigate unblinding rates in an RCT using a THC-containing cannabinoid, we re-contacted 54 out of 97 participants of the CANNA-TICS trial who had participated in our study center in Hannover. Of the 54 participants, 53 could be reached. Of these, one participant (2%) stated that she had unblinded herself intentionally during the treatment phase, and another three patients (6%) reported intentional unblinding after the end of the treatment. Noteworthy, two patients provided discrepant information and denied self-unblinding during the interview, although during study/clinic visits they had reported having done so. Thus, based on all available information, three participants (6%) unblinded themselves intentionally during the treatment phase and another three (6%) after the end of the treatment. Accidental unblinding during the treatment phase was reported by 4/54 participants (7%) (during study visits). Since one participant reported both intentional self-unblinding (during the interview) and accidental unblinding (during a study visit), the total unblinding rate was 17% ( = 9). Of these, seven participants (13%) reported unblinding during the treatment phase. When asked in the interview whether they knew that self-unblinding would have been possible, only 34% ( = 18/53) of participants stated that they had been aware of this possibility. Thus, altogether 33% ( = 6/18) of those being informed about the possibility of self-unblinding did so and half of them (3/18, 17 %) during the treatment phase. It can be expected that in parallel to increasing knowledge of medicinal and recreational use of cannabinoids, more and more people will also be informed about the availability of THC tests. Hence, in future RCTs using THC-containing cannabinoids, researchers have to take the possibility of accidental and intentional unblinding into consideration, when designing the study.
随机双盲安慰剂对照试验（RCTs）被视为临床试验的金标准。虽然有既定标准来避免破盲，但在使用含四氢大麻酚（THC）的大麻素的RCTs中，由于THC检测广泛可得，意外破盲和故意自我破盲必须被视为一个特殊问题。为了调查使用含THC大麻素的RCT中的破盲率，我们重新联系了参与汉诺威研究中心CANNA-TICS试验的97名参与者中的54名。在这54名参与者中，53名能够联系上。其中，一名参与者（2%）表示她在治疗阶段故意自我破盲，另外三名患者（6%）报告在治疗结束后故意破盲。值得注意的是，两名患者提供了不一致的信息，在访谈中否认自我破盲，尽管在研究/临床访视期间他们曾报告这样做过。因此，根据所有可得信息，三名参与者（6%）在治疗阶段故意自我破盲，另外三名（6%）在治疗结束后破盲。4/54名参与者（7%）报告在治疗阶段意外破盲（在研究访视期间）。由于一名参与者报告了故意自我破盲（在访谈中）和意外破盲（在一次研究访视期间），总破盲率为17%（=9）。其中，七名参与者（13%）报告在治疗阶段破盲。当在访谈中询问他们是否知道自我破盲是可能的时，只有34%（=18/53）的参与者表示他们意识到了这种可能性。因此，总共33%（=6/18）被告知自我破盲可能性的人这样做了，其中一半（3/18，17%）在治疗阶段。可以预期，随着对大麻素药用和娱乐用途的了解不断增加，越来越多的人也会了解到THC检测的可得性。因此，在未来使用含THC大麻素的RCTs中，研究人员在设计研究时必须考虑到意外和故意破盲的可能性。
