Table 3.

Detailed description of interventions.

Study	Open label placebo	Verbal instruction		Procedure of OLP aministration: (1) No. of interactions (2) Length of interaction(s) (3) Provider and assessor interactions
Carvalho et al. 201630	“A typical prescribed medicine bottle of placebo pills with a label clearly marked “placebo pills” and “take 2 pills twice a day.” The placebo pills were Swedish Orange gelatin capsules filled with microcrystalline cellulose, a common inert excipient for pharmaceuticals”	“The PI explained that the placebo pill was an inactive substance, like a flour pill, that contained no active medication in it. After informed consent, all participants were asked if they had heard of the “placebo effect” and explained in an approximately 15-min a priori script, adopted from an earlier OLP study,18 the following “4 discussion points”: (1) the placebe effect can be powerful, (2) the body automatically can respond to taking placebo pills like Pavlov dogs who salivated when they heard a bell, (3) a positive attitude can be helpful but is not necessary, and (4) taking the pills faithfully for the 21 days is critical. All participants were also shown a video clip (1 min 25 s) of a television news report, in which participants in an OLP trial of irritable bowel syndrome were interviewed”		(1) 3 visits (2) 15 min a priori script; 10–15 min midpoint visit (3) Blinded nurse; interaction with unblinded Pl at midpoint
Hoenemeyer et al. 201831	“The Pl provided pre-packaged pills, clearly labeled “placebos”, along with oral and written instructions to take 2 placebo pills twice per day.”	“The 4 points were (1) placebo effects are powerful in double-blinded clinical trials and there is some evidence that placebos work even when patients know it’s placebos but we don’t know if they work when honestly prescribed for CRF; (2) placebo responses may be attributed to conditioning, expectancy and biological (e.g., neurological, genetic) factors; (3) an open mind is helpful but unrelated to outcomes that may happen automatically; and, (4) taking the placebo pills as prescribed for 21 days is important (OLP group).”		(1) 2 visits + 1 phone call at midpoint (2) Not reported (3) Blinded research assistants and blinded research specialists; interaction with unblinded Pl (an oncology behaviour specialist) at 2 visits * phone call
Kam-Hansen et al. 201432	“Study drug envelope was labeled “placebo”.”	“Take pill 30 min after migraine onset”		(1) Not reported (2) Not reported (3) No reported interactions; patient self-report
Kaptchuk et al. 201021	“Placebo pills were blue and maroon gelatin capsules filled with Avicel, a common inert excipient for pharmaceuticals”	“The provider clearly explained that the placebo pill was an inactive (i.e., ‘‘inert’’) substance like a sugar pill that contained no medication and then explained in an approximately fifteen minute a priori script the following ‘‘four discussion points:’’ (1) the placebo effect is powerful, (2) the body can automatically respond to taking placebo pills like Pavlov’s dogs who salivated when they heard a bell, (3) a positive attitude helps but is not necessary, and (4) taking the pills faithfully is critical.”		(1) 3 visits (2) 30 min initial interview process; 15 min midpoint (3) Blinded assessors; midpoint interaction with unblinded physician Pl
Kelley et al. 201237	“A visually distinctive placebo capsule”; “Blue capsules containing microcrystalline cellulose.”	“The rationale included four points: (a) in RCTs placebos are roughly 80% as effective as antidepressants; (b) classical conditioning is a possible mechanism for automatic self-healing; (c) placebo-treated patients who are more compliant have better outcomes, therefore the placebos should be taken faithfully; and (d) positive expectations increase placebo effects, but it is OK to have doubts. Although the rationale was scripted, treating psychiatrists were encouraged to deliver the rationale in a natural and supportive manner that allowed for questions and answers.”		(1) 3 visits, 1 blinded (2) Not reported (3) Blinded clinicians
Kleine-Borgmann et al. 201933	“Open-label placebo capsules containing microcrystalline cellulose twice a day for 21 days”	“All patients were shown a video providing standardized information about the placebo effect in general and recent research findings on potential beneficial effects of open-label placebo application.”		(1) 3 visits (2) Not reported (3) Blinded examiner
Nitzan et al. 202034	“Each participant received two packets containing a one month supply of placebo (120 capsules) and was instructed to take two capsules in the morning and two in the evening.”	“There will be no active component in the tablet, but there is a good chance that it will alleviate some of the depressive symptoms. Furthermore, recent scientific evidence suggests that placebo tablets can be helpful in treating various medical conditions even if a person knows they are placebos”		(1) 3 visits (2) Not reported (3) Research team-member
Pan et al. 202028	“The OLP group received a glass bottle containing the pills labelled “Placebos for menopausal hot flushes” with the original medication leaflet.”	“Each patient receives the following information about placebos: (1) the placebo effect is powerful; patients reported symptom improvement after taking placebos in double-blind drug trials, including hot flush trials. However, these participants were unaware of whether they were receiving a placebo or medicine. (2) A few studies have shown that placebos without deception can have beneficial effects. The body may react to the pill intake automatically (Depending on the patient’s prior knowledge, an example is given, e.g., the Pavlov dog or food poisoning for which certain foods cause queasiness and nausea). Being positive and believing in a positive effect can help but is not necessary. (4) Taking the pills faithfully twice a day is crucial since the custom of pill intake can contribute to the effect. Also, to the adhering instructions is important to maintain the quality of the study, i.e., if some patients would only take half their pills, we would be comparing several subgroups with the no-treatment group. (5) Finally, we do not know whether placebos without deception can reduce hot flushes. Therefore, we encourage patients to simply “give it a try.”.”		(1) 4 visits (2) Relevant biopsychosocial information 10–15 min (3) Assessments by blinded research assistant; clinical consultation with unblinded clinician at each visit
Sandler et al. 201019	A “visually distinctive capsule “	“Children and parents were told explicitly at the beginning of the study that the inert capsule was a placebo that contained no active pharmaceutical ingredients. Also, they were told the study was designed to determine if the procedure was effective. In keeping with a proof of concept study, we were neutral regarding the likelihood of success. Positive expectancy was maintained, however, by referring to the placebo both as a placebo and as a Dose Extender. If either the child or parent raised questions about possible mechanisms of placebo effects, we briefly discussed possibilities of mind–body interactions, expectancy and conditioning (described as “a kind of learning”).”		(1) Not reported (2) Not reported; children randomised to the OLP group had an additional discussion of the placebo with the study physician (3) Interaction with physician Pl; assessments by unblinded parents and blinded school teachers
Sandler and Bodfish 200820	“A visually distinctive placebo capsule”	“This little capsule is a placebo. Placebos have been used a lot in treating people. It is called ‘Dose Extender’. As you can see, it’s different from __ (give name of prescribed stimulant). Dose Extender is something new. It has no drug in it. I can promise you that it won’t hurt you at all. It has no real side effects. But it may help you to help yourself. It may work well with your, kind of like a booster to the dose of. That’s why it’s called a Dose Extender.”		(1) Not reported (2) Not reported (3) Interaction with unblinded physician Pl; assessments by unblinded parents and blinded schoolteachers
Schaefer et al. 201638	“Participants in the placebo group received a white tube containing 28 placebo pills. The tube was labeled with the logo of the local university and the following information: ‘placebo pills (28), take one in the morning and one before night for 14 days	“We explained that placebos are inactive substances and that they contain no medications. Participants were further told that although placebos contain no medication, placebo effects may still be powerful. The effect was explained to them by pointing out that the body may automatically respond to taking placebo pills, like Pavlov’s dogs that salivated when they heard the bell. In addition, they were told that a positive attitude may be helpful for the placebo effect, but is not necessary. Last, they were told that those participants who were in the placebo group needed to take the placebos faithfully		(1) 2 visits (2) Not reported (3) Not reported, nor wether blinded
Schaefer et al. 201835	See above (Schaefer et al., 2016)	With briefing: See above (Schaefer et al., 2016)	Without briefing: “placebos were explained as containing no medications, similar to a sugar pill.”	(1) 2 visits (2) Not reported (3) Experimenter
Zhou et al. 201836	“Placebos were small red tablets containing microcrystalline cellulose, FD&C Red 40 and ethyl alcohol, manufactured and labeled by an FDA-registered pharmacy.”	“Following a written script, investigators described the study rationale, possible impact of placebo on CRF, prior evidence of the impact of placebo on symptoms including fatigue, and answered participants’ questions”		(1) 1 visit + 2 phone calls (2) Not reported (3) Research assistants