Bayever 1984.

Methods	Duration From 1977 to 1982 Randomization Allocation compatible with 'Mendelian randomization' Treatment Number of arms: 2 Type of intervention Test arm: MSD‐HSCT Control arm: IST Median follow‐up time Not reported
Participants	Setting Single‐center study United States Eligibility criteria Less than 25 years of age All 35 patients who had an HLA‐identical donor underwent bone marrow transplantation The 22 patients without an HLA‐identical donor received ATG therapy Number of patients MSD‐HSCT arm: N = 35 IST arm: N = 27 Age MSD‐HSCT arm: median 17 (range 2 to 24) years IST arm: median 15 (range 1 to 23) years Gender MSD‐HSCT arm: males 67% (23 of 35) patients IST arm: males 68% (15 of 22) patients Further inclusion criteria to define SAA Criteria for the diagnosis of SAA: bone marrow cellularity < 25% (with < 30% myeloid cells) and peripheral counts, taken on 3 occasions 24 hours apart, including at least 2 of the following: granulocytes < 0.5 X 109/L, platelets < 20 x 109/L, reticulocytes < 20 X 109/L
Interventions	MSD‐HSCT arm Patients received MSD‐HSCT from 1977 to 1982 Interval from diagnosis to treatment median 60 (range 9 to 2520) days Previous therapy: none reported Discontinuation of treatment not reported, no criteria defined Bone marrow was the stem cell source for all recipients IST arm Patients received IST from 1977 to 1982 Interval from diagnosis to treatment median 58 (range 8 to 2669) days Previous therapy: none reported; quote from the introduction section: "(...)whether treatment with ATG should be the primary therapeutic approach(..)" Discontinuation of treatment not reported, no criteria defined ATG: treatment consisted of 1 dose of equine anti‐human thymocyte globulin per day (20 mg/kg/day) for 8 days Ciclosporin: no treatment
Outcomes	Primary outcome Overall survival such as 2‐year actuarial survival Secondary outcomes Treatment‐related mortality denoted as causes of death after treatment such as graft rejection, acute GVHD, chronic GVHD, interstitial pneumonia, veno‐occlusive disease, hemorrhage, infection Adverse events denoted as complications after treatment such as acute GVHD, chronic GVHD, interstitial pneumonia, serum sickness, hypertension Karnofsky performance scores of surviving patients Response to treatment denoted as hematologic recovery with normal peripheral blood counts within 6 months of treatment (both treatment arms)
Notes	No competing interest reported, funding, grants, and awards received from non‐for profit organizations Supported in part by the National Cancer Institute, National Institutes of Health, and by the US Public Health Service
Risk of bias
Bias	Authors' judgement	Support for judgement
Blinding of outcome assessment (detection bias) All outcomes	High risk	Blinding of outcome assessor was not reported for any outcome
Incomplete outcome data (attrition bias) All outcomes	Low risk	The data for all 57 included patients have been analyzed and it is conceivable that the outcome data were complete (Table 3 of the article)
Selective reporting (reporting bias)	Unclear risk	Relapse was reported for the IST group but not for the MSD‐HSCT group. "All eight patients with severe aplastic anemia who responded after ATG therapy are alive. One of the responders has relapsed but still survives(..)"
Other bias	High risk	The authors reported the study results at an early time point before all planned data had been gathered. "We present this interim report(...)". No other bias such as competing interest or cross‐over.
Comparable baseline characteristics	Low risk	There were no differences of baseline characteristics between the 2 treatment groups, in particular with reference to age (Table 1 of the article)
Concurrent control	Low risk	Data for the control group were collected during the same time period as the data for the test group. "Fifty‐seven consecutive patients younger than 25 years with severe aplastic anemia underwent treatment at UCLA between November 1977 and October 1982."