Alternative randomised trial designs

Everyone knows about a “standard” 2-arm randomised trial, but there are lots of variations on the basic design. Many will be familiar with the more common alternative trial designs, such as cross-over, cluster, multi-arm trials and within-person - these are introduced here. However, beyond these there are many, many alternatives, of which many but by no means all are some sort of adaptive trial.

Below is a not-too-serious list of more unusual/fancier sounding randomised trial designs that I have come across. Inclusion in no way means either I endorse or infer anything good or bad about the design. A more serious point is that the same designs have been presented as new with different labels - and probably will be again.

If you have a name for the list, do send me the reference and I will add.

A non-exhaustive list of less common and fancy Sounding randomised trial designs  

• Adaptive designs (D'Amico et al. Adaptive designs: lessons for inflammatory bowel disease trials. Journal of Clinical Medicine. 2020;9(8):2350. doi: 10.3390/jcm9082350) [there are many variations on this theme – some of the more common, interestingly named ones are listed below]
• Adaptive signature design (Adaptive Signature Design- review of the biomarker guided adaptive phase -III controlled design - PubMed (nih.gov)) [also known as Biomarker adaptive signature design/two-stage adaptive signature design]
• Adaptive hypothesis designs (D'Amico et al. Adaptive designs: lessons for inflammatory bowel disease trials. Journal of Clinical Medicine. 2020;9(8):2350. doi: 10.3390/jcm9082350)
• Adaptive enrichment designs (Stallard. Adaptive enrichment designs with a continuous biomarker. Biometrics. 2023;79:9-19. doi: 10.1111/biom.13644)
• Basket (Park et al. Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols. Trials. 2019;20(1):572. doi: 10.1186/s13063-019-3664-1)
• Bayesian decision-theoretic sequential response-adaptive randomization design (A Bayesian decision-theoretic sequential response-adaptive randomization design - PubMed (nih.gov))
• Biomaker stratified trials (Kaplan. The FOCUS4 design for biomarker stratified trials. Chinese Clinical Oncology. 2015; 4(3):35. doi: 10.3978/j.issn.2304-3865.2015.02.03)
• Block response-adaptive randomization (Familywise error rate control for block response-adaptive randomization - PubMed (nih.gov))
• Cohort multiple RCT (Abaid et al. Reducing publication bias through trial registration. Obstetrics and Gynecology. 2007;109(6):1434-1437. doi: 10.1097/01.AOG.0000266557.11064.2a)
• Complex innovative design (Blagden et al. Effective delivery of Complex Innovative Design (CID) cancer trials—A consensus statement. British Journal of Cancer. 2020;122:473-482. doi: 10.1038/s41416-019-0653-9)
• Comprehensive cohort trial (Wasmann et al. Partially randomised patient preference trials as an alternative design to
  randomised controlled trials: systematic review and meta-analyses. BMJ Open. 2019;9:e031151. doi: 10.1136/
  bmjopen-2019-031151)
• Crossed design (Martindale C. The therapist-as-fixed-effect fallacy in psychotherapy research. Journal of Consulting & Clinical Psychology. 1978;46(6):1526-30. doi: 10.1037//0022-006x.46.6.1526)
• Dog leg (Hooper R, Bourke L. The dog-leg: an alternative to a cross-over design for pragmatic clinical trials in relatively stable populations. Int J Epidemiol 2014;43:930-6.)
• Double Randomisation (Does CBT for Youth Anxiety Outperform Usual Care in Community Clinics? An Initial Effectiveness Test - PMC (nih.gov))
• Expertise based trial (Devereaux et al. Need for expertise based randomised controlled trials. BMJ. 2005;330. doi: 10.1136/bmj.330.7482.88)
• Fully randomised preference trial (Preference Collaborative Review Group. Patients' preferences within randomised trials: systematic review and patient level meta-analysis. BMJ. 2008;31;337:a1864. doi: 10.1136/bmj.a1864)
• Group sequential design (An Investigation of the Shortcomings of the CONSORT 2010 Statement for the Reporting of Group Sequential Randomised Controlled Trials: A Methodological Systematic Review | PLOS ONE)
• Hierarchical design (Martindale C. The therapist-as-fixed-effect fallacy in psychotherapy research. Journal of Consulting & Clinical Psychology. 1978;46(6):1526-30. doi: 10.1037//0022-006x.46.6.1526)
• Multi-arm mult-stage (MAMS) (Noor et al. Uptake of the multi-arm multi-stage (MAMS) adaptive platform approach: a trial-registry review of late-phase randomised clinical trials. BMJ Open. 2022;12(3):e055615. doi: 10.1136/bmjopen-2021-055615)
• N-of-1 trial (Collette and Tombal. N-of-1 trials in oncology. The Lancet Oncology. 2015;16(8):885-886. doi: 10.1016/S1470-2045(15)00062-5)
• Non-randomised surgeon design (Endoscopic resection of gastrointestinal submucosal lesions: a comparison between strip biopsy and aspiration lumpectomy - PubMed (nih.gov))
• Play the winner (Rosenberger. Randomized play-the-winner clinical trials: review and recommendations. Controlled Clinical Trials. 1999;20(4):328-42. doi: 10.1016/s0197-2456(99)00013-6)
• Partially randomised patient preference trial (Wasmann et al. Partially randomised patient preference trials as an alternative design to randomised controlled trials: systematic review and meta-analyses. BMJ Open. 2019;9:e031151. doi: 10.1136/bmjopen-2019-031151)
• Partially/fully nested trial design (Roberts et al. Design and analysis of trials with a partially nested design and a binary outcome measure. Statistics in Medicine. 2016;35(10):1616-1636. doi: 10.1002/sim.6828)
• Patient preference design (Wasmann et al. Partially randomised patient preference trials as an alternative design to randomised controlled trials: systematic review and meta-analyses. BMJ Open. 2019;9:e031151. doi: 10.1136/bmjopen-2019-031151)
• Platform (Park et al. An overview of platform trials with a checklist for clinical readers. Journal of Clinical Epidemiology. 2020;125:1-8. doi: 10.1016/j.jclinepi.2020.04.025)
• Randomised CRM (Koopmeiners and Wey. The randomized CRM: an approach to overcoming the long-memory property of the CRM. Journal of Biopharmaceutical Statistics. 2017;27(6):1028-1042. doi: 10.1080/10543406.2017.1293076)
• Registry-based trials (Li et al. Registry-based randomized controlled trials- what are the advantages, challenges, and areas for future research? Journal of Clinical Epidemiology. 2016;80:16-24. doi: 10.1016/j.jclinepi.2016.08.003)
• Response-adaptive randomization design (How to Do Response-adaptive Randomization (RAR) if You Really Must - PubMed (nih.gov))
• Sample size re-estimation design (Trends in Adaptive Design Methods in Dialysis Clinical Trials: A Systematic Review - PMC (nih.gov))
• Seamless two-stage / two-stage adaptive seamless design (Chow and Tu. On two-stage seamless adaptive design in clinical trials. Journal of the Formosan Medical Association. 2008;107(12):S52-S60. doi: 10.1016/S0929-6646(09)60009-7)
• Sequential multiple assignment randomization trial (SMART) design (Doorenbos et al. Sequential multiple assignment randomization trial designs for nursing research. 2019;42(6):429-435. doi: 10.1002/nur.21988)
• Single case design (Kazdin. Single‐case experimental designs: Characteristics, changes, and challenges. Journal of the Experimental Analysis of Behavior. 2021;115(1):56-85. doi: 10.1002/jeab.638)
• Staircase cluster randomised trial (The staircase cluster randomised trial design: A pragmatic alternative to the stepped wedge - Kelsey L Grantham, Andrew B Forbes, Richard Hooper, Jessica Kasza, 2023 (sagepub.com))
• Stepped wedge (Brown CA, Lilford RJ. The stepped wedge trial design: a systematic review. BMC Med Res Methodol. 2006 Nov 8;6:54. doi: 10.1186/1471-2288-6-54. PMID: 17092344; PMCID: PMC1636652.)
• Surgeon randomised/randomised-surgeon design (Minimally invasive dynamic hip screw: prospective randomized trial of two techniques of insertion of a standard dynamic fixation device - PubMed (nih.gov))
• Trials within cohorts (TWiC) (Trials within Cohorts)
• Tracker trials (Lilford et al. Trials and fast changing technologies: the case for tracker studies. BMJ. 2000;320:43. doi: 10.1136/bmj.320.7226.43)
• Two-stage enrichment design (Frieri et al. Design considerations for two-stage enrichment clinical trials. Biometrics. 2022. doi: 10.1111/biom.13805)
• Two stage (patient preference) - including Rucker/Wennberg designs (King et al. Conceptual framework and systematic review of the effects of participants' and professionals' preferences in randomised controlled trials. Health Technology Assessment. 2005;9(35). doi: 10.3310/hta9350)
• Umbrella (Park et al. Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols. Trials. 2019;20(1):572. doi: 10.1186/s13063-019-3664-1)
• Zelen’s (single and double-consent)/Randomised consent designs (Simon et al. Zelen design clinical trials: why, when, and how. Trials. 2021;22(1):54. doi: 10.1186/s13063-021-05517-w  & Schellings et al. Randomized consent designs in randomized controlled trials: Systematic literature search. Contemporary Clinical Trials. 2006;27(4):320-332. doi: 10.1016/j.cct.2005.11.009)