The evidence base for emergency use authorizations for COVID-19 treatments: A rapid review.

Background and Aims: During the COVID-19 pandemic, US Food and Drug Administration (FDA) permitted emergency use authorizations (EUAs) for vaccines/treatments with promising data. Eight treatments were issued EUAs by May 31, 2021; one of these was approved (Remdesivir for certain populations) and two were revoked (chloroquine phosphate/hydroxychloroquine and bamlanivimab) by September 30, 2021. The aim of this study is to find out what evidence the EUAs were based on and how many studies were published while they remained active (up to September 30, 2021). Methods: A review of published clinical studies for the 6 months before each EUA was issued, and the time after (until September 30, 2021, or until revoked). PubMed and the identified systematic reviews were the sources for identifying published literature. Results: The number of clinical studies published pre-EUA varied from a single case study (for chloroquine phosphate/hydroxychloroquine) to numerous studies of multiple types (for convalescent plasma). Four treatments had a single randomized controlled trial (RCT) as evidence (bamlanivimab monotherapy, REGN-COV, bamlanivimab + etesevimab, sotrovimab) and two also had other study types (remdesivir and baricitinib). The number of clinical studies published post-EUA (for those active on September 30, 2021) was widely varied. Eighteen RCTs were published for Convalescent plasma, while Remdesivir had eight. Baricitinib, REGN-COV, and bamlanivimab + etesevimab all had one, but none were published for sotrovimab. Conclusion: The number of trials for treatments with EUAs was limited in all cases before the EUA was issued, and in most cases for those with EUAs ongoing at the end of September 2021. The presence of EUAs may discourage participation in relevant clinical trials, which delays the widespread implementation of evidenced-based therapies. Large, robust RCTs should be completed, such as the RECOVERY trial in the United Kingdom, to quickly find the answers desperately required during a pandemic.

Effect of financial voucher incentives provided with UK stop smoking services on the cessation of smoking in pregnant women (CPIT III): pragmatic, multicentre, single blinded, phase 3, randomised controlled trial.

OBJECTIVE: To examine effectiveness, cost effectiveness, generalisability, and acceptability of financial incentives for smoking cessation during pregnancy in addition to variously organised UK stop smoking services. DESIGN: Pragmatic, multicentre, single blinded, phase 3, randomised controlled trial (Cessation in Pregnancy Incentives Trial phase 3 (CPIT III)). SETTING: Seven UK stop smoking services provided in primary and secondary care facilities in Scotland, Northern Ireland, and England. PARTICIPANTS: 944 pregnant women (age ≥16 years) who self-reported as being smokers (at least one cigarette in the past week) when asked at first maternity visit, less than 24 weeks' gestation, and notified to the trial team by routine stop smoking services. INTERVENTIONS: Participants in the control group were offered the standard stop smoking services, which includes the offer of counselling by specially trained workers using withdrawal orientated therapy and the offer of free nicotine replacement therapy. The intervention was the offer of usual support from the stop smoking services and the addition of up to £400 ($440; €455) of LoveToShop financial voucher incentives for engaging with current stop smoking services or to stop smoking, or both, during pregnancy. MAIN OUTCOME MEASURES: Self-reported smoking cessation in late pregnancy (between 34 and 38 weeks' gestation) corroborated by saliva cotinine (and anabasine if using nicotine replacement products). Results were adjusted for age, smoking years, index of multiple deprivation, Fagerström score, before or after covid, and recruitment site. Secondary outcomes included point and continuous abstinence six months after expected date of delivery, engagement with stop smoking services, biochemically validated abstinence from smoking at four weeks after stop smoking date, birth weight of baby, cost effectiveness, generalisability documenting formats of stop smoking services, and acceptability to pregnant women and their carers. RESULTS: From 9 January 2018 to 4 April 2020, of 4032 women screened by stop smoking services, 944 people were randomly assigned to the intervention group (n=471) or the control group (n=470). Three people asked for their data to be removed. 126 (27%) of 471 participants stopped smoking from the intervention group and 58 (12%) of 470 from the control group (adjusted odds ratio 2.78 (1.94 to 3.97) P<0.001). Serious adverse events were miscarriages and other expected pregnancy events requiring hospital admission; all serious adverse events were unrelated to the intervention. Most people who stopped smoking from both groups relapsed after their baby was born. CONCLUSIONS: The offer of up to £400 of financial voucher incentives to stop smoking during pregnancy as an addition to current UK stop smoking services is highly effective. This bolt-on intervention supports new guidance from the UK National Institute for Health and Care Excellence, which includes the addition of financial incentives to support pregnant women to stop smoking. Continuing incentives to 12 months after birth is being examined to prevent relapse. TRIAL REGISTRATION: ISRCTN Registry ISRCTN15236311.

Bah humbug! Association between sending Christmas cards to trial participants and trial retention: randomised study within a trial conducted simultaneously across eight host trials.

OBJECTIVES: To determine the effectiveness of sending Christmas cards to participants in randomised controlled trials to increase retention rate at follow-ups, and to explore the feasibility of doing a study within a trial (SWAT) across multiple host trials simultaneously. DESIGN: Randomised SWAT conducted simultaneously across eight host trials. SETTING: Eight randomised controlled trials researching various areas including surgery and smoking cessation. PARTICIPANTS: 3223 trial participants who were still due at least one follow-up from their host randomised controlled trial. INTERVENTION: Participants were randomised (1:1, separately by each host trial) to either received a Christmas card in mid-December 2019 or to not receive a card. MAIN OUTCOME MEASURE: Proportion of participants completing their next follow-up (retention rate) within their host randomised controlled trial. RESULTS: 1469 participants (age 16-94 years; 70% (n=1033) female; 96% (813/847) white ethnicity) across the eight host randomised controlled trials were involved in the analysis (cut short owing to covid-19). No evidence was found of a difference in retention rate between the two arms for any of the host trials when analysed separately or when the results were combined (85.3% (639/749) for cards versus 85.4% (615/720) for no card; odds ratio 0.96, 95% confidence interval 0.71 to 1.29; P=0.77). No difference was observed when comparing just participants who were due a follow-up in the 30 days after receiving the card (odds ratio 0.96, 0.42 to 2.21). No evidence of a difference in time to complete the questionnaire was found (hazard ratio 1.01, 95% confidence interval 0.91 to 1.13; P=0.80). These results were robust to post hoc sensitivity analyses. The cost of this intervention was £0.76 (€0.91; $1.02) per participant, and it will have a carbon footprint of approximately 140 g CO2 equivalent per card. One benefit of this approach was the need to only submit one ethics application. CONCLUSIONS: Sending Christmas cards to participants in randomised controlled trials does not increase retention. Undertaking a SWAT within multiple randomised controlled trials at the same time is, however, possible. This approach should be used more often to build an evidence base to support selection of recruitment and retention strategies. Although no evidence of a boost to retention was found, embedding a SWAT in multiple host trials simultaneously has been shown to be possible. STUDY REGISTRATION: SWAT repository https://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,846275,en.pdf#search=SWAT%2082.