OLP studies
| Study | Disorder/Problem | N | Duration | Control group(s) | Study structure: (a) Blinding: assessment (b) Blinding: visit midpoint (c) Placebo briefing before randomisation | Structure OLP: (a) No. of interactions (b)Length of interaction(s) (c) Length of intervention (d) Provider and assessor interactions | Structure control(s): (a) No. of interactions (b) Length of interaction(s) (c) Length of intervention (d) Provider and assessor interactions |
| Aulas and Rosner (2003)24* | Minor anxiety and somatoform symptoms | 34 | 7 days | None | (a), (b), (c): Not applicable—single group study, no randomisation | (a) Not reported (b) Not reported (c) 1 week (d) Physician | No control group |
| Carvalho et al,7 2016† | Chronic lower back pain | 83 | 3 weeks | TAU | (a) A registered nurse blinded to treatment assignment conducted all assessments (b) Unblinded PI: reminded participants receiving placebo pills about the 4 discussion points and reminded participants in the TAU arm that they could start the placebo pills at the end of the 3 weeks (c) 4 discussion points on placebo effects | (a) 3 visits (b) 15 min a priori script; 10–15 min midpoint visit (c) 3 weeks (d) Blinded nurse; interaction with unblinded PI at midpoint | (a) 3 visits (b) 15 min a priori script; 10–15 min midpoint visit (c) 3 weeks (d) Blinded nurse; interaction with PI unblinded at midpoint |
| Hoenemeyer et al,11 2018† | Fatigue among cancer survivors | 74 | 3 weeks | TAU | (a) All assessments were performed by a research assistant blinded to randomisation allocation (b) Unblinded PI (an oncology behaviour specialist) phone call to inquire about patients’ health changes and answer questions (c) 4 discussion points on placebo effects | (a) 2 visits+1 phone call at midpoint (b) Not reported (c) 3 weeks (d) Blinded research assistants and blinded research specialist; interaction with unblinded PI (an oncology behaviour specialist) at 2 visits+phone call | (a) 2 visits+1 phone call at midpoint (b) Not reported (c) 3 weeks (d) Blinded research assistants and blinded research specialist; interaction with unblinded PI (an oncology behaviour specialist) at 2 visits+phone call |
| Kam-Hansen et al,21 2014* | Episodic migraine | 66 | 7 migraine attacks | No treatment drug (Maxalt) | (a) All study personnel were blind to treatment allocation (b) Not applicable (c) Intake instructions and content of Maxalt and placebo | (a) Not reported (b) Not reported (c) 6 attacks after baseline attack (d) No reported interactions; patient self-report | (a) Not reported (b) Not reported (c) 6 attacks after baseline attack (d) No reported interactions; patient self-report |
| Kaptchuk et al,32 2010† | Irritable bowel syndrome | 80 | 3 weeks | NT | (a) All assessments were performed by a researcher who was blind to treatment assignment (b) Blinded with research assessors. Potential for unblinding in interaction with physician PI; patients receiving placebos received a short reminder regarding the ‘4 discussion points’. In the no treatment arm, patients were encouraged and thanked for helping make a successful study (c) 4 discussion points on placebo effects | (a) three visits (b) 30 min initial interview process; 15 min midpoint (c) 3 weeks (d) Blinded assessors; midpoint interaction with unblinded physician PI | (a) 3 visits (b) 30 min initial interview process; 15 min midpoint (c) 3 weeks (d) Blinded assessors; midpoint interaction with unblinded physician PI |
| Kelley et al,18 2012† | Major depressive disorder | 20 | 4 weeks (intervention group); 6 weeks (waitlist control) | Waitlist control | (a) Blinded clinicians assessed patients at baseline and every 2 weeks thereafter (b) Not applicable (c) 4 discussion points on placebo effects | (a) 3 visits, 1 blinded (b) Not reported (c) 4 weeks (d) Blinded clinicians | (a) 4 Visits‡, 1 blinded (b) Not reported (c) 6 weeks (2 weeks waitlist, 4 weeks OLP) (d) Blinded clinicians |
| Locher et al,17 2017*† | Heat pain experiment with healthy participants | 160 | 1.5 hours | NT OLP- DP | (a) Unblinded study investigators knew the allocation code of participants at the start of the trial (b) Not applicable (c) No briefing before randomisation | (a) 1 visit (b) Not reported (c) Not reported (d) Unblinded researchers | For all controls: (a) 1 visit (b) Not reported (c) Not reported (d) Unblinded researchers |
| Mathur et al,20 2018† | Wound healing in healthy volunteers | 65 | 10 days | NT | (a) Blinded co-investigator dermatologist assessing wound healing at visit 3 (b) Not reported (c) 4 discussion points on placebo effects | (a) 3 visits (b) 25 min for the first session; 10 min for first follow-up; 15 min for final follow-up (c) 10 days (d) Blinded co-investigator dermatologist | (a) 3 visits (b) 25 min for the first session; 10 min for first follow-up; 15 min for final follow-up (c) 10 days (d) Blinded co-investigator dermatologist |
| Park and Covi (1965)23* | Neuroticism | 14 | 1 week | None | (a), (b), (c): Not applicable—single group study, no randomisation | (a) 2 visits (b) 75–90 min for initial visit. Time not provided for second visit (c) 1 week (d) 1 unblinded psychiatrist | No control group |
| Sandler and Bodfish, 200810§ | Juvenile ADHD | 26 | 4 weeks baseline and 4 weeks dose reduction | Full dose group Partial dose group (ie, medication dose reduction without OLP) | (a) School teachers were the only blinded raters during the study (b) Not applicable (c) No briefing before randomisation | (a) Not reported (b) Not reported (c) 8 weeks (d) Interaction with unblinded physician PI; assessments by unblinded parents and blinded school teachers | For all controls: (a) Not reported (b) Not reported (c) 8 weeks (d) Interaction with unblinded physician PI; assessments by unblinded parents and blinded school teachers |
| Sandler et al,22 2010§ | Juvenile ADHD | 99 | 4 weeks baseline and 4 weeks dose reduction | Full dose group Partial dose group (ie, medication dose reduction without OLP) | (a) Unblinded parents; blinded school teachers (b) Not applicable (c) No briefing before randomisation | (a) Not reported (b) Not reported; children randomised to the OLP group had an additional discussion of the placebo with the study physician. (c) 8 weeks (d) Interaction with physician PI; assessments by unblinded parents and blinded school teachers | For all controls: (a) Not reported (b) Not reported (c) 8 weeks (d) Interaction with physician PI; assessments by unblinded parents and blinded school teachers |
| Schaefer et al,9 2016† | Allergic rhinitis | 25 | 2 weeks | TAU | (a) Not reported (b) Not applicable (c) 4 discussion points on placebo effects before randomisation | (a) 2 visits (b) Not reported (c) 2 weeks (d) Not reported, nor whether blinded | (a) 2 visits (b) Not reported (c) 2 weeks (d) Not reported, nor whether blinded |
| Schaefer et al,8 2018*† | Allergic rhinitis | 46 | 2 weeks | TAU+, TAU−, OLP− | (a) The experimenter was blind to treatment assignments. (b) Not applicable (c) Basic information about placebos | (a) 2 visits (b) Not reported (c) 2 weeks (d) Experimenter | For all controls: (a) 2 visits (b) Not reported (c) 2 weeks (d) Experimenter |
| Zhou et al,19 2018* | Cancer-related fatigue | 40 | 3 weeks | NT | (a) Not reported if research assistants who conducted phone calls were blinded. Other assessments: not reported (b) Not applicable (c) Study rationale, information on possible impact of placebo on cancer-related fatigue, prior evidence of the impact of placebo on symptoms including fatigue | (a) 1 visit+2 phone calls (b) Not reported (c) 3 weeks (d) Research assistants | (a) 1 visit+2 phone calls (b) Not reported (c) 3 weeks (d) Research assistants |
*Open placebo is provided not as a dose-extender, and without the aforementioned four discussion points.
†Open Placebo is provided with four discussion points identical or very similar to what was originally discussed by Kaptchuk et al.6
‡The difference between 4 visits in control and 3 visits in OLP is due to the fact that patients initially assigned to control were later switched to the OLP condition for 4 weeks, meaning they were technically in the study for 2 weeks longer than patients initially assigned to OLP. Of note, the authors examined between-subject differences comparing 2 weeks of OLP vs 2 weeks of waitlist, as well as within-subject differences comparing before and after 4 weeks of OLP.
§Placebo issued as a dose-extender; some information about the placebo effect might be given.
DP, deceptive placebo; NT, no treatment; OLP, open label placebo; OLP−, OLP without a rationale; PI, principle investigator; RCTs, randomised controlled trials; sign., significant; TAU, treatment-as-usual.