The current paradigm for biologic initiation: a mixed-methods exploration of practices, unmet needs, and innovation opportunities in self-injection training

Figures & data

Figure 1. Remote online study and focus group design and flow

Table 1. Patient participant characteristics

Category	Biologic-Experienced Patients – Remote Ethnography (N=24)	Biologic-Naive Patients – Focus Groups (N=5)
Age Median (Range)	48 (30 to 68)	60 (49 to 75)
Gender Female	21 (87%)	4 (80%)
Race White Black or African American Hispanic or Latin Asian/Pacific Islander Native American	17 (71%) 4 (17%) 1 (4%) 1 (4%) 1 (4%)	4 (80%) 1 (20%) 0 0 0
Education Graduated high school/GED Completed some college Associate’s degree Bachelor’s Degree Master’s Degree	1 (4%) 4 (17%) 5 (21%) 8 (33%) 6 (25%)	0 1 (20%) 0 1 (20%) 3 (60%)
Employment Status Full-Time Employed Part-Time Employed Retired/Unemployed Homemaker	11 (46%) 3 (13%) 7 (28%) 3 (13%)	1 (20%) 0 4 (80%) 0
TBQ Median (Range)	67 (0 to 145)	56 (11 to 140)
Biologic Experience BxN BxE	13 (54%) 11 (46%); 1 previous therapy (7), 2 previous therapies (3), 3 previous therapies (1)
Self-Reported Diagnosis Psoriasis/Psoriatic Arthritis Rheumatoid Arthritis Multiple Sclerosis Ulcerative Colitis/Crohn’s Lupus Migraine Type 2 Diabetes Severe Asthma Hypercholesterolemia	5 (21%)^1 4 (17%)^2 3 (13%)^3 2 (8%)^4 2 (8%)^5 2 (8%)^6 3 (13%)^7 2 (8%)^8 1 (4%)^9	0 1 (20%)^10 0 0 1 (20%)^11 1 (20%)^12 1 (20%)^13 1 (20%)^14 0

Abbreviations: TBQ, Treatment Burden Questionnaire; BxN, biologic-naïve, experience only on currently prescribed biologic therapy; BxE, biologic-experienced, experience on one or more previously prescribed biologic therapies

¹(2) Humira (adalimumab), Cosentyx (secukinumab), Tremfya (guselkumab), Stelara (ustekinumab)

²(2) Humira (adalimumab), Simponi (golimumab), Enbrel (etanercept)

³Plegridy (peginterferon beta-1a), Betaseron (interferon beta-1b), Rebif (interferon beta-1a)

⁴Humira (adalimumab), Stelara (ustekinumab)

⁵(2) Benlysta (Belimumab)

⁶(2) Ajovy (fremanezumab-vfrm)

⁷(2) Victoza (liraglutide), Ozempic (semaglutide)

⁸Dupixent (dupilumab), Fasenra (benralizumab)

⁹Praluent (alirocumab)

¹⁰Plaquenil (hydroxychloroquine)

¹¹Plaquenil (hydroxychloroquine)

¹²Tylenol (acetaminophen)

¹³Metformin

¹⁴Singulair (montelukast)

Table 2. HCP participant characteristics

Category	Healthcare Provider (HCP) – Remote Ethnography (N=18)
Age Median (Range)	50.5 (32 to 69)
Gender Female	11 (61%)
Race White Black or African American Hispanic or Latin Asian/Pacific Islander Middle Eastern or North African	9 (50%) 1 (5.5%) 4 (22%) 3 (17%) 1 (5.5%)
Professional Title Physician/Physician’s Assistant (PA) Nurse Nurse Educator*	6 (33%)^15 7 (39%)^16 5 (28%)^17
Clinical Specialty Neurology Rheumatology Gastroenterology Endocrinology Cardiology Allergy/Immunology Dermatology Primary Care	1 (5.5%) 3 (17%) 1 (5.5%) 2 (11%) 2 (11%) 3 (17%) 4 (22%) 2 (11%)
Frequency of Biologic Training Daily Weekly Monthly^†	7 (39%) 10 (55.5%) 1 (5.5%)
Total Time in Current Position 1–2 years 3–5 years 5+ years	2 (11%) 3 (17%) 13 (72%)
Monthly Biologic Initiations (switching or new) 1–10 11-20 21–30 31-40 41+	7 (39%) 4 (22%) 3 (17%) 3 (17%) 1 (5.5%)
Number of Biologics Experienced in Training 1–5 6-10 11+	8 (44%) 7 (39%) 3 (17%)
Facility Geography NY, FL NJ AZ, GA, IL, MD, MA, NV, OH, PA, TN, TX	3 (17%) from each state 2 (11%) 1 (5.5%) from each state

Abbreviations: LVN, Licensed Vocational Nurse; LPN, Licensed Practice Nurse; *Nurse Educator, participants who are currently employed as a NP, RN, LVN, or LPN who are also practicing nurse educators and have experience routinely training patients to self-inject biologic medications. ^†To fill the Primary Care quota, 1 Nurse participant was accepted for ‘monthly’ training frequency.

¹⁵Physician 5 (27%); Physician’s Assistant 1 (6%)

¹⁶Registered Nurse (RN) 4 (22%); Nurse Practitioner (NP) 3 (17%)

¹⁷LVN/LPN 2 (11%); Registered Nurse (RN) 2 (11%); Nurse Practitioner (NP) 1 (6%)

Figure 2. HCP and patient reported biologic initiation time allocation

Table 3. Frequency of injection-related content relayed

Biologic Initiation Topics	HCP Frequency of Topics Discussed (N = 18)			Patient Frequency of Topics Discussed (N = 24)
	Always	Sometimes	Never	During Training	Learned on My Own	Neither
Dosing Frequency	17 (94%)	1	0	15 (63%)	9	0
Overview of Device Features	17 (94%)	1	0	10 (42%)	12	2
Post-Injection/Disposal Information	17 (94%)	1	0	9 (38%)	12	3
Storage Information	17 (94%)	1	0	11 (46%)	11	2
Rationale Behind the Instructions for Use	16 (89%)	2	0	12 (50%)	9	3
Injection Preparation Information	16 (89%)	1	1	12 (50%)	9	3
Drug Safety Information/Side Effects	16 (89%)	2	0	12 (50%)	9	3
Establishing Medication Management Routine	15 (83%)	3	0	11 (46%)	12	1
Loading vs. Maintenance Phase	15 (83%)	2	1	10 (42%)	7	7
Injection Support Resources/PSP Information	12 (67%)	5	1	10 (42%)	10	4
Managing Emotions/Injection-Related Anxiety	9 (50%)	9	0	7 (29%)	10	7
Difference in New and Prior Injection Devices	9 (50%)	9	0	8 (33%)	9	7
Information on Traveling with Biologics	9 (50%)	8	1	7 (29%)	10	7
Lifestyle Fit/Personal Impact	8 (44%)	9	1	9 (38%)	13	2
Review of Quick Reference Guide (QRG)	8 (44%)	9	1	8 (33%)	10	6
Review Full Prescribing Information (PI)	5 (28%)	10	3	7 (29%)	14	3

Abbreviations: PSP, patient support program

Figure 3. HCP correlation of topics discussed (% always) and perceived importance

Figure 4. HCP correlation of topics discussed (% sometimes) and perceived importance

Table 4. HCP live responses to self-injection videos containing use errors

Video Stimulus	Instructions for Use Language	Observed Use Error	Identification Count (N = 18)
Video #1: Humira Injection	Keep pressing the plum-colored activator button and continue to push the Pen against your squeezed, raised skin until all the medicine is injected. This can take up to 10 seconds, so count slowly to ten. Keep pushing the Pen against the squeezed, raised skin of your injection site for the whole time so you get the full dose of medicine. You will know that the injection has finished when the yellow indicator fully appears in the window view and stops moving.	[Yellow indicator hidden by fingers, lifts off thigh before checking] ‘I don’t know if I got it all the way but it’s showing.’	6 (33%)
5/6 Suggest facing viewing window toward you while injecting and verify window before lifting
‘Should inject at a 90-degree angle and watch the window, verifying the yellow has come down before removing the pen from his skin.’ N7, Dermatology
‘Should have placed the window of the injection facing toward him.’ N3, Rheumatology
‘Should wait for the yellow indicator to stop moving in the window before he pulled the pen off his skin.’ N6, Allergy/Immunology
‘Need to position it so that you can see the window on the side to watch it inject and make sure it’s finished so you don’t inadvertently withdraw it.’ P12, Dermatology
‘Have the patient look to see that the injection is complete before pulling away, he pulled away before the window showed complete injection.’ P11, Dermatology
1/6 Suggests longer count required
‘Needs to count to 15, he only counts to 10. I’m not sure he did it right, he would need further training.’ N10, Primary Care
Video #2: Enbrel Injection	Create a firm surface at the selected injection site (thigh, stomach, or outer areas of the upper arm), by using either the Stretch method or the Pinch method.	[No stretch or pinch method observed]	6 (33%)
6/6 Express no pinching or spreading method observed
‘I would pinch up some of that skin.’ NE3, Allergy/Immunology
‘He did not grab a portion of the skin to pull the skin up prior to injecting.’ N7, Dermatology
‘Did not pinch or stretch his skin.’ N6, Allergy/Immunology
‘I think pinching the skin could be helpful overall.’ P12, Dermatology
‘He should’ve pinched his skin a little bit to make a pocket for the medication.’ N9, Primary Care
‘I notice he’s not pinching the skin.’ N10, Primary Care
Video #3: Simponi Injection	Choose Injection Site – Option Lower abdomen (do not use the 2-inch area around your navel)	‘Go about an inch [points to area around navel].’	2 (11%)
2/2 Correct location of injection in the navel area
‘We do 2 inches from the belly button, and also divide his abdomen in four, like four quadrants. I would probably go a little higher or a little lower.’ NE7, Allergy/Immunology
‘Needed to do it two inches away from the belly button.’ N6, Allergy/Immunology
Video #4: Cosentyx Injection	Listen for the 2nd click, this indicates the injection is almost complete. Check the green indicator fills the window and has stopped moving. The Cosentyx Sensoready Pen can now be removed.	[Wet Injection Observed] ‘That’s weird, there’s liquid out there, quite a bit.’	12 (67%)
8/12 Suggest longer hold required and verify window before lifting
‘Allow the pen to stay flush against the skin for a few more seconds, it looks like the patient removed the pen too early for all the injection to be delivered into the subcutaneous tissue.’ N7, Dermatology
‘Somehow, he removed the injector before the injection is complete, the fluid from the injector comes out and sprayed on the thigh. Again, that’s not a good example how to inject Cosentyx. This patient needs to be trained again. Press the button, wait for the second click before removing the injector.’ P8, Gastroenterology
‘He pulled it out too soon after the second click and there’s a little medication dripping on the leg. I would talk to him about this, he needs further teaching.’ N10, Primary Care
‘Next time you inject please keep in mind you need to wait 10–20 seconds and count slowly and then remove it from the body to allow the tissues to absorb the medication.’ NE6, Endocrinology
‘They’re not sure why it did it- but it’s clear he took it out of the skin before it finished dispensing. Part of the teaching should include what to do when that happens.’ N11, Endocrinology
‘It’s not a good injection, his medicine is still coming back out of his leg. Unfortunately, this is the reality when most patients go home and do it.’ N9, Primary Care
‘I think that the patient was a little bit confused as to what the appropriate site was to actually administer the injection and whether or not they held the injection too long and whether or not it was administered properly because apparently some of the medication may have come out from the injection site.’ P7, Cardiology
‘With the liquid coming back out, maybe go into a fattier area, maybe pinch the skin. Didn’t check his window when he was done.’ NE3, Allergy/Immunology
4/12 Express this is a normal occurrence
‘A little of the medication came out of the area that was injected, which is a little bit normal unless it was a whole lot.’ NE2, Dermatology
‘I know he’s concerned about that little bit of splash back, but that’s fine, that happens.’ N4, Rheumatology
‘That’s normal, for some of the medication to come out.’ NE7, Allergy/Immunology
‘Overall, he did very well, I was not worried about the liquid at the end although he was, which may be something to discuss at his next visit.’ P12, Dermatology

All videos observed in this activity were publicly shared videos on YouTube. HCPs recorded their live responses to these videos upon initial viewing, and their recognition of use errors was defined as any verbal expression of awareness.

Table 5. Evidence-based recommendations to improve self-injection initiation

Element	Description	Study Findings	Opportunities
Spaced Repetition	Spaced repetition is an evidence-based learning technique in which training is repeated over time, with the time intervals increasing between each repetition.	When device training does occur in an office setting, it is typically a single, time-constrained event. Patients may be overwhelmed during a single visit and providing information in an incremental and iterative manner could reduce this emotional burden.	Distribute injection training over a series short, frequent sessions, rather than a single-instance event. Introduce material in increments and re-iterate important points, providing patients adequate time to absorb and retain information for the duration of their therapies.
Practice At Home	Patients are supplied demo-devices for home use and given the opportunity to practice in their actual self-injection environment without the risk of error, injury, or medication loss.	A limited number of demo-devices are available in healthcare facilities, precluding patients from taking devices home for subsequent practice. The lack of availability of demo-devices forces some HCPs to rely on actual devices for injection training and restricts patients to a single demonstration or ‘practice’ session before self-injecting actual medication.	Lessen the impact of in-office training variability by making training devices available for patients at home, either through increased supply in prescribing facilities or shipments from the pharmaceutical manufacturers directly. Demo-devices at home have the potential to facilitate teach-back instruction through alternative mediums and JIT training before real injections in the early stages of therapy.
Teach-Back Technique	Teach-back is a technique to confirm patient understanding by asking them to repeat or describe what they understand about their condition, treatment, and any instructions given during their visit to care.	Very few patients have the opportunity to return injection demonstrations to their HCP for feedback. If it does occur, it is limited to in-office training only, as little instruction occurs beyond that session.	Leverage the injection training responsibility HCPs place on pharmaceutical manufacturers and develop avenues to employ tech-back methods through video and other means to access more patients and eliminate the reliance on in-person demonstration.
Just-In-Time Reinforcement	JIT training provides the opportunity for ‘rolling refreshers’ on how to perform a procedure in real-time just prior to actual performance.	HCP participants view demo-devices in the context of one-time, in-office use, and do not consider that they could be employed beyond the initial training session. In contrast, patients note that demo-devices would be useful to have at home to reinforce proper technique and set expectations for their actual injections.	Provide patients with the resources to perform JIT reinforcement before their self-injections in early stages of therapy, especially those with longer dosing intervals. Application of JIT principles has the potential to offer patients real-time tips and recommendations they may have forgotten from previous training or actual use.
Adult Learning Principles	Adult learning principles state the need for: 1) rationale behind instruction, 2) motivation to learn, 3) consideration for past experience, 4) learning approaches that match individual backgrounds and diversities, and 5) active involvement of the adult (patient) in the learning process.	Very little formal guidance is provided to HCPs on biologic initiation, as nearly all HCPs reported relying on a trial-and-error to develop practices. Common patient communication and tailoring techniques are not consistently practiced by all HCPs and are likely established through individual heuristics rather than established standards.	Develop a structured, consistent resource for biologic initiation, centered on adult learning principles. Decrease HCP trial-and-error and establish a standard of communication strategies and instruction techniques. This resource would enable HCPs, regardless of time in practice and therapy experience, to reach similar practices in shorter time spans.
Emotional engagement	Emotional engagement is present when users feel delighted by a brand, service, or business and are enthusiastic about the functional benefits of a product. This can be obtained through consideration of individual mind-sets, preferences, and lifestyles.	Time constraints and perceived importance dictate that HCPs focus on disease activity and technical treatment logistics (dosing frequency, device features, disposal, storage), while neglecting the emotional aspects patients may experience (managing emotions, injection-related anxiety, traveling, lifestyle fit/personal impact).	Implement early patient instruction on establishing routines, managing emotions and adapting lifestyles, not solely injection mechanics and safety. Understanding technical use and clinical information is a priority, but only a portion of the overall experience. Take into account individual patient preference and concerns, and ensure patients are mentally and emotionally prepared to manage the treatment.
Peer-to-Peer Learning	Peer-to-peer learning is the dynamic of students teaching other students (or in this case patients teaching other patients). It’s an experience that involves the sharing of knowledge, ideas and experiences between individuals in similar situations.	HCPs view materials offered by the biologic brands as sufficient and frequently refer patients to these sources. However, the majority of patient participants expressed that the materials offered by biologic brands have shortcomings. They often reported that this information is ‘basic’ and ‘biased,’ displays an overwhelming amount of content and legal jargon and lacks authenticity.	Consider patient feedback on resource shortcomings and, while preserving medical accuracy of the information being relayed, produce ‘authentic’ material, aimed at showcasing actual patient experiences, the reality of injections, and potential solutions to mitigate fear and anxiety.
Rituals	Rituals are elements of a routine developed by patients to help mitigate fear and anxiety associated with self-injection, ultimately increasing their confidence. Authors suggest, empowering patients to develop their own personalized self-injection rituals could offer substantial benefit.	Training and support patients receive early in biologic initiation has a significant effect on their perceived burden of treatment and ease of use with self-injections. Regardless of training experience, patients experience negative physical and mental responses during early stages of treatment.	Explore rituals, as they may be of interest to pharmaceutical manufacturers when developing patient support materials.