Risk of dosing errors in ART treatment: user experience of single- vs multi-use follitropin alfa pens

Figures & data

Table 1. Critical steps identified from the Instructions for Use (IFU) for each product

IFU	BEMFOLA®	OVALEAP®	GONAL-F®
Preparing your pen/injection	Hold pen by its sides and attach the needle by clicking it into place Do not push the dosage knob while attaching the needle Dosage knob pushed until activation bar with small arrow disappears Hear a click? Small amount of liquid was splashed out?	Twist to unscrew the pen body from the cartridge holder Twist the cartridge holder off the shaft The dose indicator is set to ‘0’ Carefully twist inner plunger (opposite direction to arrows) Insert cartridge into the pen with colored metal clip pointing forward Slowly & carefully push the two parts of the pen together Screw the cartridge holder onto the shaft Ensure the two parts are securely joined; do not overtighten Firmly screw the outer protector with the needle onto the cartridge holder ensuring it is straight Turn dosing dial by two ‘clicks’ and remove inner needle cap Hold pen with needle pointing upwards and slide injection button in the direction of the needle A drop will form at the tip of the needle – if not, repeat	Verify that Dose Feedback Window is set to ‘0’ Get a new needle Screw-threaded tip of the Gonal-f® pre-filled pen into outer needle cap until feeling a light resistance Look closely at tip of needle for tiny drop(s) of fluid YES: Proceed to ‘Setting the dose’ prescribed NO: Gently turn the dose setting knob clockwise until it reads ‘25’ in the Dose Feedback Window Press the dose setting knob as far as it will go A tiny drop of liquid will appear at the tip of the needle Verify dose window = ‘0’
Setting the dose	Dosage knob turned until desired dose is set in the display window Dosage knob not pushed yet	Set required prescribed dose by turning the dosing dial	Turn the dose setting knob until your intended dose shows in the Dose Feedback Window Set the dose that was prescribed
Injecting the dose	Do not push the dosage knob while inserting the needle Push slowly but continuously, until the dose bar disappears Wait for 5 seconds before the injection needle is removed	Slide the injection button in the direction of the needle and hold it pressed down until the dose indicator is on ‘0’ Wait for 10 seconds after the injection before withdrawing the needle	Verify that Dose Feedback Window displays correct dose Press the dose knob down as far as it will go and hold it to complete the full injection (the dose number shown in the Dose Feedback Window turns back to ‘0’) After ≥5 seconds, pull the needle out of the skin while keeping the dose setting knob pressed down
After the injection	No critical steps identified for Bemfola®	Only needed if the patient completes a partial injection Inspect dose window and identify position on dose window, e.g. 37.3 plus 1 line To inject this dose, take new cartridge and repeat all steps from ‘Preparing Your Pen/Injection’	Only needed if the patient completes a partial injection Dose Feedback Window will indicate the missing amount needed to inject using a new pen Repeat ‘Before you start using your pen’ through to ‘Preparing your pen/injection’ with a second pen Set the dose to the missing amount you recorded in the treatment diary or the number still displayed in the Dose Feedback Window on your previous pen, then inject

Figure 1. Injection pens provided for nurse testing: (a). Gonal-f® pen, 300IU; (b). Ovaleap® pen and 300IU cartridge; (c). Bemfola® single-use pens, 2 × 150IU. Relative product sizes are shown to scale

Figure 2. Dosing scenarios and pen products tested by patients in the usability study: (a). Gonal-f®; (b). Ovaleap®; (c). Bemfola®. Relative product sizes are shown to scale

Table 2. Study participants and summary of inclusion criteria

Study participants	GERMANY (Berlin)	UK (London)	FRANCE (Paris)	SPAIN (Barcelona)	TOTAL
Nurses	5	5	4	5	19
Patients	6	6	6	6	24
TOTAL	11	11	10	11	43
Inclusion criteria
Patients Minimum 18 years old All wanted to get pregnant, but were facing difficulties All had already met with a physician concerning their fertility problems All were considering hormonal treatment with pens, but were still naïve concerning the use of pens (not in therapy yet) Local language speaker			Nurses Minimum 2 years’ fertility clinic experience All worked in a fertility center or in a clinic/unit/office responsible for fertility treatments, with minimum 300 cycles per year All were responsible for patient pen training, with minimum 10 per month Maximum 60 years old Local language speaker

Figure 3. Critical error rates recorded during the pen usability study. Critical error rate (%) = [(total number of critical steps omitted or carried out incorrectly) / (total number of critical steps)] × 100.Figure 4

Figure 4. Results of preference rankings in the handling tests. Data show the product preferred in each aspect of handling characteristics by (a) Nurses (N = 19) and (b) Patients (N = 24)