AMDRT 2004.

Methods	Multicentre study: 10 sites. Randomisation stratified by lesion type (new or recurrent CNV following thermal laser photocoagulation) and blood (< 50% or >= 50%).
Participants	Country: USA. Number randomised: 88. New CNV arm: mean age 77 years (range 63 to 92). Recurrent CNV arm: mean age 80 years (range 73 to 78). 58% women. Inclusion: visual acuity of at least 20/320 and subfoveal CNV (occult CNV, minimally classic CNV or predominantly classic CNV) with fibrosis if present comprising < 50% of the lesion not amenable to treatment. AMD confirmed by drusen > 63 μm or focal hyperpigmentation in either eye or evidence of CNV, geographic atrophy or serous detachment of the pigment epithelium in the non study eye.
Interventions	Treatment (n=41):External beam radiotherapy 20 Gy (5 x 4 Gy) 6 mv. Control : observation (n=25) or sham radiotherapy (n=22) depending on centre.
Outcomes	Primary outcome: loss of 3 or more lines of visual acuity. Secondary outcomes: lesion size graded on fluorescein angiography. side effects.
Notes	Age‐related macular degeneration radiotherapy trial (AMDRT). Funded by the National Eye Institute and each participating institution. Sample size 100 patients; stopped early because of a low rate of recruitment.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	"Randomised treatment assignment schedules, stratified by lesion type (new or recurrent) and status of blood (<50% or >=50% of the lesion) were generated for each clinical site" Page 819, methods, enrolment and randomisation procedures, 2nd paragraph.
Allocation concealment?	Low risk	“After required examinations and photography were completed, an eligibility checklist was faxed to the Coordinating Center. The enrolling ophthalmologist and clinic coordinator verbally confirmed eligibility of the patient by telephone with a Coordinating Center staff member. For centres performing sham radiotherapy, sealed, black‐lined security envelopes containing a randomized assignment were provided to the ophthalmology clinical staff. At enrollment, the clinic co‐ordinator confirmed with the Co‐ordinating center the assignment of the patient to the next sequentially numbered envelope for the appropriate strata. The sealed envelope was sent to the Radiation Oncology Department and opened by the radiation oncologist and radiation physicist immediately before treatment. For centers not performing sham radiotherapy, the coordinator called the Co‐ordinating center to obtain the treatment assignment" Page 819, methods, enrolment and randomisation procedures, 1st and 2nd paragraphs.
Blinding? Visual acuity	High risk	“At the outset, each center had the option to choose sham radiotherapy or observation only as the control treatment for active radiotherapy. Three centers chose sham radiotherapy.” Page 819, methods, 1st paragraph.  “During follow‐up, examiners were masked to the patient’s treatment assignment” Page 820, 1st paragraph. It was obvious which group received radiotherapy. Only 3 out of 10 centers chose to perform sham radiotherapy. Only some of the control group (22/47) received sham radiotherapy. Visual acuity assessment was masked to treatment group, however, it is possible that an individual’s performance on the visual acuity test could be influenced by their perceptions as to which treatment they received.
Blinding? Lesion size on fluorescein angiography	Low risk	“Certified photographers performed all fundus photography and fluorescein angiography following SST protocols. Initial visit photography was required within 42 days of enrollment. Expert readers at the FPRC, masked to treatment assignment, reviewed all baseline photographs and angiograms for eligibility.” Page 820, photography and fluorescein angiography, 1st and 2nd paragraphs. Although the report does not explicitly state that photograph graders were masked to treatment assignment when considering follow‐up photographs and angiograms it is highly likely that they were and it is unlikely that a participant’s knowledge of treatment group would influence the appearance of photographs or fluorescein angiograms.
Incomplete outcome data addressed? All outcomes	High risk	31/41 (76%) in treatment group seen at 12 months; 31/47 (66%) of the control group seen at 12 months. 12 enrolled patients were subsequently considered ineligible; all these patients included in the analysis. 5 patients did not get the treatment they were assigned but were analysed in the original group to which they were assigned.   “Among all missed visits, the most common reason for not completing the visit was patient refusal; other reasons were illness and transportation problems” The follow‐up in the control group was rather low which is why this is marked “no”.
Free of selective reporting?	Unclear risk	See additional table 3.
Free of other bias?	Unclear risk	"Patient enrollment began in January 2000 with a goal of 100 patients. One center had been conducting a single center clinical trial with the same protocol and consent procedures and had enrolled 23 patients before their multi‐center certification; these patients are included in the analysis. In September 2001, the Data and Safety Monitoring Committee (DSMC) recommended that recruitment be halted because of a low rate of enrollment." Page 819, methods, second paragraph.