Kadir 2000.

Methods	This was a randomised, double‐blind, placebo‐controlled, cross‐over single centre study.
Participants	A total of 39 women were randomised to the study. 10 of these women did not receive any study medication for various reasons. Out of the remaining 29, one was known to have taken her first dose of study medication but did not complete a follow up PBAC and therefore was not included in the ITT population (n ¼ 28). Four women did not complete the second period of treatment and thus the per protocol population consisted of 24 women. Inclusion criteria: women aged 18 – 50 years with diagnosed inherited bleeding disorders, including mild to moderate VWD (vWF:Ac ¼ 5 – 50 IU dL)1), heterozygote FXI‐deficient women (FXI ¼ 15 – 70 IU dL)1) or carriers of haemophilia (FVIII ¼ 5 ‐ 50 IU dL)1), and objectively confirmed menorrhagia (PBAC score > 100) were included in the study. Exclusion criteria: women with type 2B VWD, a history of renal and hepatic impairment, endocrine disorders, thromboembolic disease and nasal pathology interfering with absorption of the spray, including rhinitis, nasal polyp or significantly deviated septum were excluded from the study, as were those with a known hypersensitivity to desmopressin or chlorobutanol (or both). Other exclusion criteria included use of hormonal contraception or intrauterine contraceptive devices, medical treatment for menorrhagia and hysteroscopy, and/or dilatation and curettage in the previous 3 months.
Interventions	During each of the study periods, the women were instructed to take 1 spray in each nostril (i.e. 300 µg of desmopressin ‐ Octim® spray and the same amount of saline for the placebo)) twice daily during the second and third day of the period for 2 months.
Outcomes	1. Measurement of MBL primary outcome for the study and for this review. Method: the women were instructed to maintain a diary for each treatment cycle in which the PBAC, was provided and the woman was advised to tick or complete wherever appropriate. The PBACs were then scored by one gynaecologist using the scoring system used by Higham (Higham 1990). The study has reported median PBAC scores rather than mean for placebo and desmopressin. 2. Adverse events (the second primary outcome of the review). 3. Participant preference (the review did not have this outcome). 4. Absenteeism from work.
Notes	The use of diuretics, carbamazepine, non‐steroidal anti‐inflammatory agents, platelet‐impairing medications, clofibrate and chlorpropamide were prohibited during and 10 days before the study. This study was supported by the Ferring pharmaceutical company.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Blinded randomisation" mentioned but method of sequence generation mot mentioned.
Allocation concealment (selection bias)	Unclear risk	"Blinded randomisation" mentioned but how allocation was concealed not stated.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Doube blinded.
Incomplete outcome data (attrition bias) All outcomes	High risk	Out of 39 recruited women outcome data available for 29.
Selective reporting (reporting bias)	Low risk	All outcomes reported.
Other bias	High risk	This study was supported by the Ferring pharmaceutical.