DCCT2 1993.
| Methods |
Parallel randomised controlled clinical trial Randomisation ratio: 1:1 Superiority design |
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| Participants |
Inclusion criteria: age: 13‐39 years, IDDM for 1‐15 years, urinary albumin excretion < 200 mg/24h, very mild‐to‐moderate nonproliferative retinopathy Exclusion criteria: hypertension, hypercholesterolaemia, severe diabetic complications or medical conditions Diagnostic criteria: insulin dependence, as evidenced by deficient C‐peptide secretion |
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| Interventions |
Number of study centres: 29 Treatment before study: |
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| Outcomes | Outcomes reported in abstract of publication: retinopathy, microalbuminuria, nephropathy, neuropathy, severe hypoglycaemia | |
| Study details |
Run‐in period: Study terminated before regular end: yes ("In June 1993, after an average follow‐up of 6.5 years (range, 3 to 9), the independent data monitoring committee determined that the study results warranted terminating the trial") |
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| Publication details |
Language of publication: English Funding: non‐commercial and commercial (various corporate sponsors, see DCCT 1987) Publication status: peer‐reviewed journal/full article |
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| Stated aim of study | Quote from publication: "Will intensive therapy prevent the development of diabetic retinopathy in patients with no retinopathy (primary prevention), and will intensive therapy affect the progression of early retinopathy (secondary intervention)? Although retinopathy was the principal study outcome, we also studied renal, neurologic, cardiovascular, and neuropsychological outcomes and the adverse effects of the two treatment regimens" | |
| Notes | IDDM: insulin‐dependent diabetes mellitus | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote from protocol: "For large samples, the Urn procedure minimizes the potential for selection bias, i.e., minimizes the potential that the clinics may influence the assignment of treatments to subjects by guessing which treatment will be assigned next. The Urn procedure, however, does not guarantee equal numbers of subjects in each treatment group. Rather, the probability of a substantial imbalance in the numbers assigned to each treatment is virtually eliminated by this procedure. Within either the primary prevention or secondary intervention trial, the probability that more than 370 of the 700 subjects would be assigned to either group is only 0.0073. The exact number of subjects to be randomised to either group is unknown because the exact number of subjects to be recruited within each clinic‐retinopathy stratum is unknown." Quote from publication: "Randomization was stratified according to the primary‐prevention and secondary‐intervention cohorts at each centre". Comment: urn randomizations procedures (Wei 1988) |
| Allocation concealment (selection bias) | Low risk | Quote from protocol: "The Coordinating Center disclosed the random assignment of each patient to the clinic via telephone at the time of randomizations".The list of random assignments will be kept confidential and accessible only to the Coordinating Center staff at the time of randomizations. Randomization into one of the two treatment groups will be accomplished by a telephone call to the Coordinating Center after all criteria for entry into the study have been satisfied and documented at the Coordinating Center. At the time of randomizations, the next treatment assignment for that subjects clinic‐retinopathy stratum is communicated by telephone to the treatment centre staff, with written verification to follow." Comment: allocation concealment considered appropriate |
| Blinding of participants and personnel (performance bias) Objective Outcomes | Low risk | Quote from publication: "The two treatment regimens will, of necessity, be conducted in an unmasked manner.” ; “With the exception of HbA1c, all centrally determined outcome measurements will ordinarily be masked from the investigator responsible for the treatment regimens and from the subjects.“ Comment: treatment assignment not blinded, risk of bias considered low for objective outcomes |
| Blinding of participants and personnel (performance bias) Subjective Outcomes | High risk | Quote from publication: "The two treatment regimens will, of necessity, be conducted in an unmasked manner.” ; “With the exception of HbA1c, all centrally determined outcome measurements will ordinarily be masked from the investigator responsible for the treatment regimens and from the subjects.“ Comment: treatment assignment not blinded |
| Blinding of outcome assessment (detection bias) Objective Outcomes | Low risk | Quote from publication: “The Morbidity and Mortality Classification Committee classified deaths and cardiovascular events. Coding was performed without knowledge of treatment assignment, according to pre‐established criteria". Comment: objective outcomes were assessed in a blinded manner |
| Blinding of outcome assessment (detection bias) Subjective Outcomes | Unclear risk | Comment: due to the open design of the trial it is likely that it was not possible to have a blinded assessment of all subjective outcomes |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote from publication: "Each subject will then be included in the assigned treatment group in all statistical analyses regardless of the eventual therapeutic course. Thus subjects who fail to comply with or who are unable to complete the assigned treatment regimen will nevertheless be included in the originally assigned group for statistical analyses" Comment: ITT analysis |
| Selective reporting (reporting bias) | Low risk | Comment: no reason to assume selective reporting found |
| Other bias | Low risk | Comment: no other risks of bias found |