The results of the clinical trials in healthy volunteers and surveys in patients with MS indicate that the 29G/5-bevel needle currently used for the injection of IFN β-1a, 44 or 22 mcg sc tiw, is an improvement over the previous 27G/3-bevel needle in terms of pain, ease of insertion and patient satisfaction. Based on the 5040 needle pricks administered in the two clinical trials of healthy volunteers, it appears that not only can individuals discriminate between different needles, based on the gauge, bevel geometry and shield material, but they also thought that the 29G/5-bevel needle was an improvement over the previous 27G/3-bevel needle in terms of subjective pain score on the VAS and VB-VAS. These results are supported by the five surveys in patients with MS who have experience of injections of IFN β-1a, 44 or 22 mcg sc tiw.
When interpreting the results of the clinical trials and the patient surveys, there are a number of precautions that should be noted. The patient surveys are only intended to provide supportive evidence to the more rigorously designed clinical trials. The surveys were unblinded, differed in size (3/5 surveys had fewer than 100 patients), and the results are based on subjective questionnaires, which asked slightly different questions and had different multiple-choice answer options. However, the consistent results between the surveys and the clinical trials support the assertion that the 29G/5-bevel needle is an improvement over the 27G/3-bevel needle, regardless of whether the individuals were healthy volunteers receiving fluid-less injections or patients with MS receiving injections of IFN β-1a. When considering the results of the clinical trials, it should be noted that the VAS and VB-VAS are subjective measures, and the descriptors were modified to accommodate the assessments being made. However, the strong, positive correlation between the VB-VAS and the Gracely Box SL pain scale, which was unmodified, as well as the strong, positive correlation between the VB-VAS and the VAS demonstrate the convergent validity of these pain scales and consistently support the assertion that injections with the 29G/5-bevel needle are associated with less pain than with the 27G/3-bevel needle.
The apparent ability of individuals to discriminate between needles seen in this study is supported by similar findings in a previous study of patients with Type I diabetes and healthy volunteers . Patients with diabetes, who were experienced in carrying out daily sc injections, as well as healthy volunteers, were able to discriminate between good or poor quality needlepoints. This suggests that differences in a needle's gauge and the number of bevels will have a readily noticeable effect on a patient's injection experience. Furthermore, the meta-analysis of the two trials we conducted demonstrate that the VAS, VB-VAS and Gracely Box SL pain scale appear to be reliable tools for assessing individuals' perceived pain associated with injection.
The ranking of the needles on the VAS and VB-VAS scales for pain and ease of insertion indicate that the needle-shield material contributes to an individual's perception of pain associated with injections. The additional analysis we conducted showed that a needle's geometry (gauge and number of bevels) reduced individuals' perceived pain by 40% when comparing the needle currently used to inject IFN β-1a, 44 or 22 mcg sc tiw, with the previous needle. The needle-shield material appeared to account for some of this difference, as demonstrated by the difference in pain scores for the 29G/5-bevel needle with TPE shield and the same needle with the rubber shield versus the 27G/3-bevel needle with rubber shield. The most likely explanation for this difference is that the TPE shield caused less abrasion to the needle during insertion than the rubber shield. The type of silicone lubricant used for injections might have influenced individuals' perceived pain, but further experiments would be required to explore these possibilities.
Although the VAS and Gracely Box SL pain scale were developed and validated for the assessment of pain related to disease conditions and care deliveries, we have successfully managed to discriminate between the performances of different hypodermic needles. We developed the VB-VAS from these two existing pain scales specifically to assess injection-related pain. Indeed, the overall effectiveness of the VB-VAS to detect small differences in noxious skin stimuli, as induced by needle pricks, was the same as the VAS and Gracely Box SL scale. Convergent validity of the three pain scales was confirmed by strong, positive correlations between the VB-VAS and the Gracely Box SL pain scale and the VAS and the VB-VAS. Further evidence of convergent validity of the VB-VAS and VAS was provided by the identical rankings on both scales of the different types of needle, from least painful (29G/5-bevel needle with TPE shield) to the most painful (27G/3-bevel needle with rubber shield). Together, these results indicate that the three pain scales are reliable tools to discriminate needles according to the level of nociceptive stimulation that is elicited.
The findings of the five international surveys in patients with MS support those of the clinical trials of needle pricks in healthy volunteers. A fundamental difference between the surveys and the trials is that the patients with MS in the surveys were injected with IFN β-1a, 44 or 22 mcg sc tiw, and were experienced at self-administration using the previous 27G/3-bevel needle. Importantly, unique questions in the US survey indicated that, in addition to reduced pain, patients reported less bruising, burning and stinging, and fewer injection-site reactions when injecting IFNβ-1a, 44 or 22 mcg sc tiw, using the 29G/5-bevel needle than when using the 27G/3-bevel needle.
To address the potential concern that the thinner 29G/5-bevel needle may be damaged more easily than the 27G/3-bevel needle, a needlepoint drop test was also performed (data on file). After each needle was dropped 90 times from a known height on to a polypropylene sheet, 84% of 29G/5-bevel needles remained free from needlepoint defects compared with only 33% of 27G/3-bevel needles. Thus, despite being sharper and thinner, this engineering study suggests that the 29G/5-bevel needle is less prone to accidental damage during routine use. This is particularly important as injections of IFN β-1a are self-administered by patients with MS.
The efficacy of IFN β-1a, 44 or 22 mcg sc tiw, in the treatment of MS is well established through clinical trials such as the Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) trial and the EVidence of Interferon Dose-response: European North American Comparative Efficacy (EVIDENCE) trial [6–9]. It is expected that the 29G/5-bevel needle will result in additional treatment benefits by improving compliance and patient satisfaction. Of the DMDs that are currently approved for the treatment of patients with relapsing forms of MS, only IFN β-1a, 44 or 22 mcg sc tiw, is supplied to patients in a ready-to-use, pre-filled syringe that is pre-fitted with the 29G/5-bevel needle and TPE shield. In comparison, other formulations of IFN β are administered using thicker needles fitted with rubber shields and/or reconstitution is required before patients can inject.