Description of stepped wedge design trials studying drugs or vaccines (n=7): review of literature reviews and trial registries
| Health condition and intervention | Date, country | Design (randomisation unit) | Primary outcome | Data collection | Planned number of subjects | No. of steps/clusters |
|---|---|---|---|---|---|---|
| The Gambia Hepatitis Study8 12 45 Hepatitis B vaccination for prevention of liver cancer | 1987, Gambia | Repeated cross-sectional design Cluster randomisation (regions) | Incidence of liver cancer and chronic liver disease (up to 30–40 years) | Indirect: cancer registry and surveillance throughout the Gambia for cases of cirrhosis and cancer | Intervention: 60 000 Control: 60 000 | 17/17 |
| HPTN 0548 12 61 *Provision of nevirapine to pregnant HIV+ women (prevention of mother to child transmission) | 2003, Zambia and Uganda | Repeated cross-sectional design Cluster randomisation (health clinics) | Proportion of HIV+ women and infants using nevirapine | Direct but no follow-up Cord blood sample, maternal and infant nevirapine uptake Anonymised samples | Intervention: 304 Control: 304 | 2/16 |
| THRio study8 12 16 34 Isoniazid preventive treatment for TB in HIV+ men | 2005, Brazil | Open cohort Cluster randomisation (HIV clinics) | TB incidence | Indirect: captured every six months through regular extraction of information from patients records | Unclear | 15/29 |
| Grant† Isoniazid preventive treatment for TB in HIV+ men8 21 | 2005, South Africa | Closed cohort study Individual randomisation | TB episodes | Indirect: health service information system Patients’ records, hospital admission and employment records | 1655 | 1655/1655 |
| Washington state expedited partner treatment project Expedited patient-delivered partner therapy (azithromycin±cefixime, condoms) for sexually transmitted bacterial infections12 62 | 2006, USA | Open cohort Cluster randomisation (health jurisdiction) | Prevalence of chlamydia infection and gonorrhoea in women | Indirect: chlamydia test positivity through the infertility prevention project or planned parenthood Public health reporting of gonorrhoea in women | Unclear | 4/23 |
| Preventive malaria treatment of children in Senegal‡ Sulfadoxine-pyrimethamine+amodiaquine for malaria in children (3–59 months of age) | 2008, Senegal | Open cohort Cluster randomisation (health post) | All-cause mortality Incidence of malaria by passive case detection | Six monthly households surveys for birth, deaths, socioeconomic status Malaria incidence through passive surveillance (health posts, health centres and hospitals) | 100 000 | 4/54 |
| Operational Research for Cryptococcal Antigen Screening (ORCAS)§ Cryptococcal screening and fluconazole treatment in HIV patients entering antiretroviral therapy with CD4<100 | 2012, Uganda | Repeated cross-sectional design Cluster randomisation (clinics) | Retention in care Single blind (outcomes assessor) | Direct: active follow-up Six-month survival collected via active follow up and with contact tracing of those lost to follow-up | 3000 | 9/18 |
*Hughes: Protocol only (never implemented).
†Grant: use the stepped wedge design as a way to have staggered recruitment.
‡Clinicaltrial.gov NCT00712374.
§Clinicaltrial.gov NCT01535469.
HPTN, HIV Prevention Trials Network; TB, tuberculosis.