Melmed 2015.

Study characteristics
Methods	A multi‐centre (13 centres in the USA), adaptive, phase 1b/2a dose‐ranging placebo‐controlled study was performed to evaluate the safety and efficacy of human placenta‐derived cells (PDA‐001) inparticipants with moderate‐to‐severe Crohn’s disease between August 2010 and November 2011. Follow‐up period: 2 years (wk 1,2,4,6,12,24 then every 6 months till 24 months).
Participants	Moderate to severe Chron’s CDAI score (220‐450 ) Active inflammation on colonoscopy or elevated fecal calprotectin and inadequate response to conventional therapy at enrolment and visual evidence of mucosal inflammation within 3 months of enrollment by colonoscopy. An elevated fecal calprotectin (>162.9 mg/g) could also serve as evidence of mucosal inflammation, but no patients were enrolled based on this criterion. Fifty participants were enrolled (safety analysis, 50 participants; efficacy analysis, 48 participants). Four subjectsparticipants received 8 units of PDA‐001 (phase 1b study); 46 participants were subsequently randomised to 1 or 4 units of PDA‐001 or placebo (phase 2a study). The age of the participants was ≥18‐75 years old.
Interventions	Participants received 8 units of PDA‐001 (cenplacel‐L) (1.5X108 cells per unit) in the phase 1b open‐label study. (not included in the analysis as it is non‐randomised). Intervention group:  1 unit, or 4 units of allogenic PDA‐001 (2 infusions 1 week apart) systemic infusion. The cells were extracted from placental tissue. Doses: Group I: 1.5x108, Group II: 6x108 Control group: patients in the placebo group received "vehicle control without any cells"(Infusion was done twice on 0 and 7 days) "Concomitant therapy with stable doses of immunomodulators and/or biologics was permitted."
Outcomes	The primary endpoint was induction of clinical response (> or =100 points and/or 25% decrease in CDAI) at 4 and 6 weeks.
Notes	This manuscript included 2 phases: phase 1b not included in the analysis as it is non‐randomised, phase 2a included in the analysis as it is randomised. “The study was suspended before the last 2 enrolled subjects were randomized because of safety events” Trial start date: August 2010  Trial ending date: November 2011 Trial registry number: NCT01155362 Funding Source: sponsor: Celularity Incorporated. Collaborator: Celgene Corporation. Conflict of interest:  G. Y. Melmed has provided consulting services for AbbVie, Amgen, Celgene, Given Imaging, Janssen, Luitpold Pharmaceuticals, and UCB and has received research funding from Pfizer, Prometheus Laboratories, and Shire Pharmaceuticals. W. M. Pandak has received research grants from Bayer, Novartis, MannKind, Bristol‐Myers Squibb, Ocera, Salix, GlobeImmune, Scynexix, Genzyme, Intermune, Hoffman Laroche, SciClone, Wyeth, Merck, UCB, Celgene, Centocor, Millenium, Osiris, Exilixis, AtheroNova, Pfizer, and GlaxoSmithKine. J. Valentine has received research funding from Pfizer, Celgene, Abbott, Bristol‐Myers Squibb, Takeda, Genentech, and the National Institutes of Health and has provided speaking services for AbbVie.  D. Schwartz has provided consulting services for AbbVie, UCB, Janssen, Takeda, Celgene, and Tigenix and has received research funding from AbbVie and UCB.  S. Lichtiger has provided consulting services for Jansen, AbbVie, Prometheus Laboratories, and Shire and has received research funding from Jansen, Pfizer, Osiris, and Millenium. B. Sands has provided consulting services for AbbVie, Amgen, AstraZeneca, Avaxia Biologics, Bristol‐Myers Squibb, Janssen Biotech, Luitpold Pharmaceuticals, MedImmune, Pfizer, Puretech Ventures, Salix, Shire, Takeda, Topivert Pharma, and Vedanta Biosciences; has received research funding from AbbVie, Amgen, Celgene, Janssen R&D, Millennium Pharmaceuticals, Pfizer, and Prometheus Laboratories; has received honoraria for lecturing in a CME program from IMEDEX, Strategic Consultants International, Focus Medical Communications, Curatio CME Medical Institute/Huntsworth Health NA, Creative Educational Concepts, and Scripps; has received honoraria as an associate editor from the American Gastroenterological Association Institute; and holds stock in Avaxia Biologics, a non‐publicly traded company.  R. Richards has provided speaking services to AbbVie. K. Johnson, R. Hariri, and S. Fischkoff are full‐time employees of Celgene Corporation with stock and stock options. The remaining authors have no conflicts of interest to disclose.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Subsequent subjects were enrolled into the phase 2a study and were randomly assigned to receive placebo, 1 unit (1.5X108 cells), or 4 units (6X108 cells) of PDA‐001 in a double‐blinded fashion" The method of randomisation is not stated clearly.
Allocation concealment (selection bias)	Unclear risk	The method of allocation was not mentioned.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Phase IIa: It was mentioned that it was a "double blinded study". also; "IP (investigational product was covered with an opaque bag to maintain blinding and administered peripherally through a volumetric pump over 2 hours."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Mostly blinded due to blinding of personnel and patients.
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT analysis was done. "one subject withdrew consent before the wk 4 efficacy endpoint, and a second subject did not provide the efficacy assessment at wk 4”
Selective reporting (reporting bias)	Low risk	Both primary and secondary outcomes match the protocol.
Other bias	Low risk	No differences in baseline characteristics.