Table 3 Examples of clinical trials that have used the different designs

Parallel groups

• Phosphodiesterase-5 inhibition for pulmonary hypertension in heart failure [31]

• Vigabatrin in infantile spasms due to tuberous sclerosis (comparative parallel design) [27]

• Stiripentol in Dravet syndrome (placebo controlled parallel design) [28]

Factorial

• Aspirin and simvastatin for pulmonary arterial hypertension [35]

Cross-over

• Amantadine in Huntington disease [40]

• Oral sildenafil therapy in severe pulmonary artery hypertension [45]

• Sirolimus therapy to halt the progression of ADPKD [42]

Latin square

• Plasma exchange for induction and cyclosporine A for maintaining remission in Wegener’s granulomatosis [47]

• Assessment of disease flare in patients with systematic lupus erythematosus [33]

N-of-1

• Amitriptyline in fibromyalgia [34]

• Tramadol to treat chronic cough [37]

• L-arginine in ornithine transcarbamylase deficiency carrier [32]

Delayed start

• Rasagiline in Parkinson’s Disease [16, 41]

Randomised placebo-phase

• Low dose phenelzine in the chronic fatigue syndrome [39]

Stepped wedge

• Long-term efficacy of HBV vaccine to prevent liver cancer and chronic liver disease [49]

• School-based anti-smoking campaign, (delivered by one team of facilitators who travel to each school)

• Sure Start programme in the UK (http://www.ness.bbk.ac.uk)

Randomised withdrawal

• Withdrawal of hydroxychloroquine sulfate in systemic lupus erythematosus [48]

• Etanercept in children with polyarticular juvenile rheumatoid arthritis [38]

• Vigabatrin withdrawal randomized study in children with epilepsy [26]

• Antipsychotic withdrawal with Alzheimer’s Disease [25]

• Stiripentol withdrawal design in children with partial epilepsy [29]

Early escape

• Intravenously golimumab in patients with active rheumatoid arthritis [36]

• Pain control for post-operative pain [46]

Three-stage

• Etanercept in children with polyarticular juvenile rheumatoid arthritis [15, 38]

Adaptive randomisation

• Prevention of postoperative venous thromboembolism in digestive surgery [43, 44]

• Reduction of maternal-infant transmission of Human Immunodeficiency Virus Type 1 with zidovudine [30]

• No example found for the ‘drop the loser’ design