Human factors engineering and design validation for the redesigned follitropin alfa pen injection device

Figures & data

Figure 1. The redesigned follitropin alfa pen injection device.

Figure 2. The risk management process for addressing use-related risks with the redesigned follitropin alfa pen.

Figure 3. Modification of the redesigned pen device. Change from conical (A) to cylindrical (B) needle cap to mitigate use error observed in the pre-validation studies.

Table 1. Demographic characteristics and prior injection experience of participants in the validation studies.

A) Characteristics	Validation study		Mitigation validation study
	Infertility patients (n = 18)	Significant others (n = 15)	Infertility patients (n = 16)	Significant others (n = 15)
Age, mean (SD), years	33.8 (4.05)	35.7 (4.85)	34.1 (5.23)	35.3 (6.70)
Range	(29 – 43)	(30 – 46)	(24 – 40)	(25 – 49)
Female, n (%)	18 (100)	0 (0)	16 (100)	1 (6.7)
Spouse/SO participating, n (%)	17 (94.4)	15 (100)	15 (93.8)	15 (100)
Years of infertility, mean (SD)	2.9 (2.06)	NA	2.1 (1.42)	NA
Range	(0.58 – 7.0)	NA	(0.25 – 5.00)	NA
Indicated for gonadotropins, n (%)
Both	9 (50.0)	7 (46.7)	5 (31.3)	5 (33.3)
In vitro fertilization	6 (33.3)	5 (33.3)	9 (56.3)	8 (53.3)
Ovulation induction	3 (16.7)	3 (20.0)	2 (12.5)	2 (13.3)
Education level, n (%)
High school graduate	4 (22.2)	5 (33.3)	4 (25.0)	6 (40.0)
College graduate	13 (72.2)	7 (46.7)	9 (56.3)	7 (46.7)
Professional/advanced degree	1 (5.6)	3 (20.0)	3 (18.8)	2 (13.3)
Right hand dominance, n (%)	18 (100)	12 (80.0)	15 (93.8)	13 (86.7)
Experience with injection,* n (%)	13 (72.2)	6 (40.0)	10 (62.5)	7 (46.7)
FSH product	8 (44.4)	2 (13.3)	7 (43.8)	5 (33.3)
Other fertility medications	11 (61.1)	3 (20.0)	8 (50.0)	2 (13.3)
Other disorders	2 (11.1)	2 (13.3)	1 (6.3)	0 (0)
Injection device used, n
FSH pen	4	1	3	2
FSH pen and syringe	4	1	3	2
FSH syringe	0	0	1	1
Other fertility medication syringe	11	3	8	2
Other disorder pen	0	1	0	0
Other disorder syringe	2	1	1	0
Number of injections,*^,‡ n
1	1	0	1	0
2	2	1	6	1
3	5	1	2	1
≥ 4	3	4	0	5
Missing/unknown	2	0	1	0
B) FN characteristics	Validation study (n = 16)		Mitigation validation study (n = 16)
Age, mean (SD), years	39.4 (12.64)		37.6 (11.06)
Range	(25 – 59)		(23 – 56)
Female, n (%)	16 (100)		16 (100)
FN professional at infertility center, n (%)	16 (100)		16 (100)
Years as a FN, mean (SD)	9.9 (7.27)		7.7 (5.60)
Range	(1.1 – 23)		(0.25 – 17)
Right-hand dominance, n (%)	12 (75)		14 (87.5)
Works directly with patients, n (%)	16 (100)		16 (100)
Involved in injectable gonadotropin training (both pen and syringe), n (%)	16 (100)		16 (100)
Trains patients to self-inject, n (%)	16 (100)		16 (100)
Number of patients trained per month, n (%)
≤ 5	2 (12.5)		1 (6.3)
6 – 10	1 (6.3)		2 (12.5)
11 – 20	4 (25.0)		2 (12.5)
21 – 30	3 (18.8)		6 (37.5)
31 – 40	3 (18.8)		4 (25.0)
41 – 50	2 (12.5)		1 (6.3)
> 50	1 (6.3)		0 (0)
Administers gonadotropins to patients, n (%)	11 (68.8)		11 (68.8)
Number of gonadotropin injections administered per month, n (%)
0	5 (31.3)		5 (31.3)
< 1	4 (25.0)		1 (6.3)
1 – 5	3 (18.8)		10 (62.5)
6 – 10	0 (0)		0 (0)
> 10	4 (25.0)		0 (0)
No prior experience with GONAL-f RFF® Redi-ject™ pen, n (%)	16 (100)		16 (100)

*Refers to self-injections for patients, and injections given to self or given to someone else for significant others.

^‡Units are cycles of fertility treatment for patients, and injections for significant others.

FN: Fertility nurse; FSH: Follicle-stimulating hormone; NA: Not available; SD: Standard deviation; SO: Significant other.

Table 2. Critical use errors in A) validation study and B) mitigation validation study.

A)	Infertility patients (n = 18)			Significant others (n = 15)	FNs (n = 16)
Injection simulations, n		126		105	112
Use errors
Primary safety, n
Setting correct dose		0		0	1*
Completing an incomplete dose		0		0	1^‡
Secondary safety, n
Minimize/eliminate needle sticks		0		0	0
Participant	Critical use-related hazard	Use error	Consequence	Mitigation required	Mitigation strategy
*FN	Setting the wrong dose	Yes	Underdosing	Yes	Device design modification
^‡FN	Not properly completing an incomplete dose	Yes	Overdosing	Yes	IFU wording change
B)		Infertility patients (n = 16)		Significant others (n = 15)	FNs (n = 16)
Injection simulations, n		80		75	80
Use errors
Primary safety, n
Setting correct dose		0		0	1*
Completing an incomplete dose		0		0	0
Secondary safety, n
Minimize/eliminate needle sticks		1^‡		0	0
Participant	Critical use-related hazard	Use error	Consequence	Mitigation required	Mitigation strategy
*FN	Inaccurate dosing	Yes	Underdosing	No	Not due to device interface design or the IFU
^‡Pt	Needle exposure	Yes	Needle stick	No	Not due to device interface design or the IFU, but to study artifact

*^,†The symbols are meant to expand on the types of use errors listed, linking the top half of each table (A and B) with the bottom half. The first part of the table summarizes the use errors and the bottom part expands the information on the error and describes the mitigation strategy.

FN: Fertility nurse; IFU: Instructions for Use; Pt: Patient.

US Food and Drug Administration. Draft Guidance for Industry and Food and Drug Administration Staff - Applying Human Factors and Usability Engineering to Optimize Medical Device Design. 2011. Available from: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm259748.htm [Last accessed 4 February 2014]

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