Table 2.

Selected implementation trials with embedded process evaluations and null results.

Study	Year	Authors	Study design	Main outcome findings	Process evaluation findings to explain null trial result
TRACS – A structured training program for caregivers of inpatients after stroke	2014	Clarke, Godfrey, Hawkins, et al. (32)	Pragmatic, 2 arm cluster RCT; 36 UK stroke units	No clinical or statistical improvement at 6 months on primary or secondary outcomes	Contextual factors, including organisational history, team relationships, external policy and service development initiatives influenced the implementation of the caregiver training program in unintended ways
WISE – Implementation of a self-management support approach (WISE) across a health system	2014	Kennedy, Rogers, Chew-Graham, et al. (33)	Pragmatic, 2 arm cluster RCT; 44 UK general practices	No effect on 12-month primary (patient) outcomes	WISE not embedded because of a perceived lack of relevance and fit to the ethos and existing work and need for resources beyond the immediacy of the participating practices
OPERA – Older People's Exercise intervention in Residential and nursing Accommodation	2014	Ellard, Thorogood, Underwood, et al. (34)	Pragmatic, 2 arm cluster RCT; 78 care homes in England	No observed effect on primary or secondary outcomes	OPERA intervention failed to change the prevailing culture that prioritised protecting clients from harm over encouraging activity Overall low attendance at group exercise sessions and those residents most likely to benefit from the intervention were least likely to engage. Low levels of staff training and few home champions for the intervention
TICD – Tailored Implementation in Chronic Diseases (5 tailored programs for chronic conditions in primary care)	2016 2017	Jäger, Steinhäuser, Freund, et al. (35) Wensing (36)	Cluster RCTs of tailored implementation programs in 5 European countries: Netherlands – cardiovascular disease; 34 general practices England – obesity; 28 general practices Norway – depression; 80 municipalities Poland – COPD; 18 general practices Germany – polypharmacy/multimorbidity; 21 general practices	Little overall observed impact on primary or secondary outcomes	Perceived relevance and credibility of practice recommendations Inability to adapt some of the contextual factors encountered, particularly at the outer context level “Determinants, interventions and contextual factors interacted in complex ways, which reduced their impact” (p.3)
FIRE – Facilitating Implementation of Research Evidence	2018	Rycroft-Malone, Seers, Eldh, et al. (37)	Pragmatic, 3 arm cluster RCT in in 4 European countries; 24 nursing homes	No significant differences in the primary outcome of documented compliance with guidance recommendations	Success of intervention implementation related to contextual factors, including fit and alignment, prioritisation and engagement, which determined a facilitator's opportunity to learn over time and enact the role
EPOCH – A multi-component quality improvement intervention to reduce mortality after emergency abdominal surgery	2018	Stephens, Peden, Pearse, et al. (38)	Stepped wedge cluster RCT; 93 UK hospitals	No improvement in primary outcomes, 90-day survival or hospital length of stay	Variable intervention fidelity at hospital level, difficult to engage clinical colleagues Quality improvement leads were attempting to deliver the intervention in challenging contexts with limited time and resources
T3 – Triage, Treatment and Transfer of Stroke Patients	2020	McInnes, Dale, Craig, et al. (39)	Pragmatic, 2 arm cluster RCT; 26 emergency departments in Australia	No improvement in 90-day health outcomes of acute stroke patients	The implementation strategy was unable to overcome system and clinician level barriers. Some contextual factors were outside the control of a senior nurse, including low medical engagement, acceptance of supporting evidence and professional boundaries