Results of a human factors experiment of the usability and patient acceptance of a new autoinjector in patients with rheumatoid arthritis.

PURPOSE: This study evaluated the human factors affecting the ease of use of a disposable autoinjector developed for subcutaneous self-injections performed by patients with chronic diseases. MATERIALS AND METHODS: This was a randomized, single-center study conducted with 65 patients with rheumatoid arthritis. Patients performed six simulated injections. Assessments of patient device acceptance and device usability were made by patient reports and independent observations of compliance with the device instruction for use (IFU) following single injections and repeated injections. RESULTS: A total of 390 simulated injections were performed. Patient device acceptance was high; more than 90% of patients found each of the tested criteria to be acceptable (>80% was required for statistical significance; P<0.016). Perceived ease of use and simplicity of the three-step process resulted in high acceptance scores: mean scores (± standard deviation) were 8.71 (±1.18) and 8.05 (±0.37), respectively, on a 0-10-point scale. Patients also expressed their acceptance with the ease and usefulness of the detection of the remaining drug in the autoinjector. In addition, 80% of patients declared that they would recommend the device to someone else. Globally, the human factors tested (age, sex, hand disability [Cochin score], extent of previous experience with self-injection [ie, expert or naïve]) had no impact on IFU device compliance. In particular, the lack of a Cochin score interaction indicated that the degree of hand disability is not a predictive factor of poor self-injection capability with this autoinjector. CONCLUSION: This study demonstrated a high level of patient acceptance for self-injection with this autoinjector among patients with rheumatoid arthritis. In particular, patients with severe hand disability were able to successfully comply with device IFU.

Echographic measurement of skin thickness in sites suitable for intradermal vaccine injection in infants and children.

Whereas the knowledge of skin thickness is essential to determine microneedle length and ensure proper administration of and better responses to intradermal vaccines, very few figures are available, especially in infants and children. Using ultrasound echography, we investigated skin thickness in 384 children aged 4-7, 12-18, and 54-66 months at potential body sites for intradermal vaccine delivery: deltoid, suprascapular, upper back, and lumbar area. The mean epidermis plus dermis thickness was significantly higher at the suprascapular than at the deltoid site (1.29mm vs. 1.22mm) and remained relatively unchanged whatever the BMI, age, sex, and skin phototype. In the 43 children aged 54-66 months, the mean skin thickness was significantly higher in the upper than in the lumbar area (1.39mm vs. 1.31mm). In this study setting, the heterogeneity in skin thickness cannot be considered sufficient to indicate various microneedle lengths for various ages or injection sites.

Evaluation of performance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy volunteers.

OBJECTIVE: A disposable autoinjector was developed for subcutaneous (SC) self-injection by patients with chronic diseases. To verify its performance and evaluate its acceptance, a clinical study was conducted in healthy volunteers, comparing SC injections performed by subjects using the autoinjector with SC injections performed by nurses using a syringe. METHODS: This was a randomized, single-center, crossover study comparing SC self-injection using an autoinjector with SC nurse-administered injection using a syringe. Two volumes (0.2 mL and 1 mL) were injected into healthy volunteers. Study objectives included assessment of the accuracy and consistency of the volume injected by the injection systems, and skin reaction and pain associated with the injection. The fluid depot in the SC tissue layer was evaluated by ultrasound. Subject acceptance was evaluated using questionnaires on attitudes and emotions towards the injection technique, and challenged by seeking the subjects' preferred system for a final study injection or future treatment. RESULTS: A total of 960 injections (480 with autoinjector, 480 with syringe) were performed in 40 subjects. There were no significant differences in mean fluid leakage and injected volumes between the systems. Pain associated with the injection was significantly lower with the auto-injector than with the syringe. Local skin reaction at the injection site was overall satisfactory. Injections were appropriately performed by all subjects. At study end, all 40 subjects preferred the autoinjector for a final study injection and for future treatment. CONCLUSION: This study indicated that the autoinjector used by the subject was similar to a syringe used by a nurse in terms of performance and safety in administering the injections, and better in terms of pain, overall acceptance, and preference.

Immunogenicity and safety of intradermal influenza vaccination in renal transplant patients who were non-responders to conventional influenza vaccination.

Seasonal influenza epidemics are associated with high morbidity and mortality particularly in high-risk patients. Conventionally administered influenza vaccines show reduced efficacy in populations with weakened immune systems such as solid-organ transplant patients. This study assesses the safety and immunogenicity of an intradermally administered influenza vaccine in renal transplant patients previously identified as non-responders to a licensed trivalent inactivated influenza vaccine (TIV). Renal transplant patients with low or no hemagglutination inhibiting (HI) antibody response to an A influenza (H3N2) vaccine strain were enrolled in a descriptive phase II, open-label, randomized, multicentre trial: 31 received an investigational intradermal TIV, and 31 received a conventionally administered TIV. Both vaccines contained 15 µg hemagglutinin (HA) per strain. The 62 study subjects were selected from 201 renal transplant patients aged 18-60 years who had been vaccinated in the previous year with a conventionally administered TIV. Vaccination was safe and well tolerated by each administration route. The immunogenicity results of this descriptive study showed ID TIV vaccination to induce HI antibody responses that trended higher in renal transplant patients than conventionally administered TIV. Our results suggest that ID influenza vaccination may offer enhanced immunogenicity and protection in persons who do not respond well to conventional TIV. Further studies should be conducted in immunocompromised populations to validate the trends for higher efficacy of ID vs. conventional route of immunization against influenza.

Safety and efficacy of novel dermal and epidermal microneedle delivery systems for rabies vaccination in healthy adults.

In the present pilot study, intradermal ID delivery systems with a BD microneedle from 1 to 3mm in length, and epidermal delivery (BD skin abrader) through abraded skin surface relative to standard intramuscular injection were evaluated. Circulating neutralizing antibodies were measured against the rabies virus after the Vero cells rabies vaccine was administered at D0, D7, D21 and D49. This clinical evaluation in 66 healthy volunteers shows that ID delivery using BD microneedle technology of 1/4 the IM antigen dose is safe, efficient and reliable, resulting in a protective seroconversion rate. In contrast, the epidermal delivery route did not produce an immune response against the rabies vaccine.

Cutaneous delivery of prophylactic and therapeutic vaccines: historical perspective and future outlook.

The skin has long been recognized as an attractive target for vaccine administration. A number of clinical studies have tested the epidermal and dermal routes of delivery using a variety of vaccines over the years. In many cases, cutaneous administration has been associated with immunological benefits, such as the induction of greater immune responses compared with those elicited by conventional routes of delivery. Furthermore, there is a growing body of evidence to suggest that such benefits may be particularly important for certain higher-risk populations, such as the elderly, the immunocompromised and cancer patients. Despite the potential advantages of vaccination via the skin, results have sometimes been conflicting and the full benefits of this approach have not been fully realized, partly due to the lack of delivery devices that accurately and reproducibly administer vaccines to the skin. The 5-year outlook, however, appears quite promising as new cutaneous delivery systems advance through clinical trials and become available for more widespread clinical and commercial use.

A novel needle for subcutaneous injection of interferon beta-1a: effect on pain in volunteers and satisfaction in patients with multiple sclerosis.

BACKGROUND: To reduce injection pain and improve satisfaction, a thinner (29-gauge [29G]), sharper (5-bevel) needle than the 27G/3-bevel needle used previously to inject interferon (IFN) beta-1a, 44 or 22 mcg subcutaneously (sc) three times weekly (tiw), was developed for use in multiple sclerosis (MS). METHODS: Two clinical trials in healthy volunteers and five surveys of patients with MS were conducted to assess whether the 29G/5-bevel needle with a Thermo Plastic Elastomer (TPE) needle shield (a sleeve that houses the tip of the needle in a secure location) is an improvement over the 27G/3-bevel needle with a rubber shield for injection of IFN beta-1a, 44 or 22 mcg sc tiw. Parameters assessed were: pain and ease of insertion (healthy volunteer and nurse responses on subjective pain measurement scales); and patient satisfaction (surveys of patients with MS). RESULTS: In healthy volunteers, the 29G/5-bevel needle with TPE shield was associated with the least perceived pain on the Visual Analog Scale (VAS) and Verbal VAS (VB-VAS); mean VAS pain scores decreased by 40% and skin penetration improved by 69% compared with the 27G/3-bevel needle with standard rubber shield (p < 0.01). Pooled results from surveys of patients with MS indicated that 63% of patients thought that injections were less painful with the 29G/5-bevel needle than the 27G/3-bevel needle. Results from individual surveys indicated that the 29G/5-bevel needle was an improvement over the 27G/3-bevel needle for ease of insertion, injection-site reactions, bruising, burning and stinging. CONCLUSION: Together these studies indicate that the 29G/5-bevel needle with the TPE shield is an improvement over the 27G/3-bevel needle with standard rubber shield in terms of pain, ease of insertion and patient satisfaction. These improvements are expected to result in improved compliance in patients with MS treated with IFN beta-1a, 44 or 22 mcg sc tiw.

Intradermal vaccine delivery: will new delivery systems transform vaccine administration?

There has been a recent resurgence of interest in intradermal vaccine delivery. The physiological advantages of intradermal vaccine delivery have been known for some time, but the difficulties associated with performing an intradermal injection have historically limited its use. New delivery systems currently in development facilitate convenient intradermal vaccination, unlocking the potential advantages of this delivery route, and potentially transforming vaccine delivery.

Evaluation of the clinical performance of a new intradermal vaccine administration technique and associated delivery system.

The advantages of intradermal (ID) vaccine administration have been well documented but difficulties in performing ID vaccination using existing techniques and equipment have limited it's clinical application. In the present study, a new ID injection technique and associated microinjection system is described and evaluated in a swine and Human models. Clinical investigation models included: injection site imaging (X-ray and 3D ultrasound echography), histological examination of injection sites, fluid injection volume accuracy measurement, subject' perceived pain and local skin reactivity were specifically developed. These evaluations showed that microinjection system can make the practice of ID vaccination easy to perform, reliable and safe, thus setting the stage for broader clinical application of ID vaccine delivery.

Echographic measurement of skin thickness in adults by high frequency ultrasound to assess the appropriate microneedle length for intradermal delivery of vaccines.

Skin thickness (epidermis-dermis) across the deltoid, suprascapular, waist and thigh as possible body sites for a new microdelivery system for intradermal (id) inoculation were evaluated using 20 MHz ultrasound echography in 205 women and 137 men aged 18-70 years, in three ethnic groups: Caucasian, Asian and Black. Mean skin thickness was 2.54 mm at the suprascapular, 2.02 mm at the deltoid, 1.91 mm at the waist and 1.55 mm at the thigh. A 1.5 mm microneedle length inserted perpendicularly to the skin surface would ensure the administration of the antigen into the dermal layer, irrespectively of subject gender, age, ethnicity and BMI. The deltoid, suprascapular and waist are the most appropriate body sites.