Press-Through Packaging versus Bold and Slim Bottle-Type Containers: A Comparative Evaluation of Drug Packaging Usability in Patients with Rheumatic Diseases

Introduction

In outpatient clinics, many older adults complain about the difficulties of drug adherence, partly because they must take a variety of drugs, often on different schedules.^1–3 They also express concerns about not being strong enough to handle drug packages. Based on national statistics on households in Japan, about half of such outpatients consist of older adults (age > 65 years) living alone, followed by older couples.^4–6 This suggests that the level of drug adherence in Japan is unclear and thus receives inadequate support; it also suggests that in many cases, drug therapy is neither appropriate nor cost-effective. In fact, the expense incurred from leftover drugs in Japan is becoming a serious problem.^7–10 Many patients need to take drugs for a long time because of chronic diseases such as diabetes mellitus and high blood pressure, and the numbers of aging patients with chronic diseases are increasing around the world.^11–13 If such patients also have impaired hand and finger function, drug packaging and devices with better usability can be essential for everyday life. In fact, usability affects not only drug adherence, but also the effectiveness (and cost-effectiveness) of therapy.^14,15 Among patients with rheumatoid arthritis (RA), one such chronic disease, appropriate drug adherence has been shown to have direct effects on therapeutic outcomes.^16,17 In addition, the number of older patients with RA is increasing based on national statistics from Japan.^18,19 Moreover, older patients with RA tend to have more complicated disease backgrounds, which makes adherence even more difficult.^20,21 In previous questionnaire surveys, patients with RA have described the difficulty of handing packages and how the use of self-made devices helps them cope with everyday drug adherence.^22–24 Of particular concern are patients with early-stage dementia, who tend to skip essential drugs because of such difficulties. In addition, actual data on drug adherence can only be collected if someone constantly stays at home with the older adult. In Japan, press-through packaging (PTP) is the most commonly used type of drug package for every generation, including older adults.^25–27 However, problems such as difficulties in opening and using single-dose packages, the tendency to drop pills, and a lack of necessary support for taking important drugs punctually are frequently observed.^28–30 In addition, the actual status of drug adherence in the home is mostly only known by visitors. As such, the actual situation regarding how older patients usually handle drugs needs to be clarified.

Objectives

In the present study, we conducted objective and subjective studies to evaluate patients’ drug adherence with PTP and conduct comparisons of usability with two new bottle-type design pill containers (Bold and Slim) (Figure 1). We also aimed to clarify the relationship between functional grip and pinch strength and usability (ie, removing pills from packages/containers). In addition, we also investigated the preferences of patients with auto-immune diseases (Table 1).

Table 1 Characteristics of the Study Participants

Figure 1 The three types of packages/containers investigated in the present study. (A) Bold bottle-type dispenser; (B) Slim bottle-type dispenser. For operation, Bold is placed on a flat surface and pressed down, while Slim is tilted and pressed at the indicated point to dispense a tablet; (C) Press-through packaging (PTP).

Materials and Methods

This study was approved by the Sadamoto Clinic Institutional Review Board (approval No. 2302) and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participating outpatients with rheumatology before the study began.

Popular PTP and newly designed bottle-type pill containers (bold bottle-type, Bold; slim bottle-type, Slim) were prepared (Figure 1). The two new design types were fabricated by Kitano Co., Ltd. (Toyama, Japan). The same two examiners (a rheumatologist and a physical therapist) conducted the practical study in the same room from November 2023 to January 2024. Pinch strength was measured using the three standard positions: 1) two-point pinch (between the tip of the thumb and the index finger); 2) three-point pinch (between the pad of the thumb and the pads of the index and middle fingers); and 3) key pinch (between the pad of the thumb and the medial–lateral surface of the index finger). Grip strength was measured using hand-held grip dynamometers (MT-100W and MT-130; SAKAI Medical, Tokyo, Japan), and pinch strength using a pinch dynamometer (MT-140; SAKAI Medical) (Figure 2).

Figure 2 Measurement apparatus and hand strength tests in the present study. Hand-held grip dynamometer with grip and pinch sensors. (A) Grip; (B) Key pinch; (C) Two-point pinch; (D) Three-point pinch. Testing followed the American Society of Hand Therapists protocol: seated posture with the shoulder adducted, elbow flexed at 90°, forearm neutral, and wrist in 0–30° extension and 0–15° ulnar deviation.

The participants were given the following instructions for use of the two new bottle-type pill dispensers; For the Bold type, push down on a flat surface (eg, palm, plate, table) to dispense a pill. For the Slim type, tilt and press a specific point on the bottle to dispense a pill. Both types can be operated with one hand. After confirming that the participants understood the instructions, they were asked to dispense two pills each from all three types of packages/containers. The time it took to complete this task was measured.

The opening status of every patient was observed and recorded using a numeric rating scale (NRS) (Table 2). Every patient provided their preference using quadratic voting (QV; 25 credits) (Table 3), which is a voting system that encourages voters to express their true relative intensity of preference between multiple options By doing so, QV seeks to mitigate the tyranny of the majority by enabling participants to trade influence over issues they do not care about for influence over issues that they do.^31–33 The usefulness of QV for evaluating preferences has been reported elsewhere.³³ In the present study, we used toy coins to demonstrate counting to aid the participants’ understanding of QV.

Table 2 Numeric Rating Scale (NRS) Used in the Present Study

Table 3 Example of Quadratic Voting Pricing

Statistical Analysis

All statistical analyses were performed using IBM SPSS Statistics (Version 25.0; IBM Corp., Armonk, NY, USA). Owing to the small sample size (n = 26) and the ordinal/discrete nature of some variables (eg, NRS, QV), nonparametric procedures were prespecified. Extraction times across PTP, Bold, and Slim were compared using the Friedman test (repeated measures), followed by Wilcoxon signed-rank tests for the planned pairwise comparisons (Bold vs PTP, Bold vs Slim) with Holm’s correction for multiplicity. Correlations between strength measures (grip, key pinch, three-point pinch, two-point pinch) and outcomes (extraction time, QV, NRS) were summarized using Spearman’s rank correlation coefficient (ρ) with exact two-sided p-values. Unless otherwise stated, data are presented as mean ± standard deviation, with the level of statistical significance set at α = 0.05. For time outcomes, negative ρ values indicate shorter (faster) extraction times.

Results

Table 4 shows the results for all 26 participants (22 women, 4 men; mean age: 72.6 ± 8.5 years; age range: 52–85 years). All participants had comorbid conditions. Among the participants with RA, hand impairment was graded as mild in 10, moderate in 9, severe in 4, and other disease in 2. The mean grip strength of all participants was 20.4 ± 7.5 kgf; six participants had a grip strength < 15 kgf. Among the pinch measures, the two-point pinch had the lowest mean value (3.6 kgf). Regarding extraction times, Bold had the shortest mean time (Bold: 5.4 ± 2.2 s; PTP: 6.6 ± 3.9 s; Slim: 6.8 ± 4.0 s), but pairwise differences were not statistically significant after adjustment. Regarding QV and NRS, no significant differences were observed among the three containers; the mean NRS values were similar (PTP: 3.8, Bold: 3.8, Slim: 3.7).

Table 4 Results of Comparisons Among All 26 Participants

Table 5 shows the correlations between grip/pinch strength and extraction time, QV, and NRS for all participants. Greater strength was associated with shorter extraction times for PTP and Slim (negative correlations), while correlations with Bold time were small. No relation was found between extraction time and grip/pinch strength for Bold. Correlations with QV and NRS were generally weak, and any nominal associations were not consistent after accounting for multiple testing.

Table 5 Spearman’s Rank Correlations Between Strength Measures and Outcomes

Comparison of Time Across Different Age Groups

Table 6 shows comparisons of mean pill extraction times for participants aged ≤ 70 and ≥ 71 years. In the ≥ 71 group, Bold had a significantly shorter extraction time (p < 0.05). No significant differences in the three items were seen in the group of participants aged ≤ 70 years.

Table 6 Comparison of Extraction Times Between Age Groups

Comparison of QV Across Different Age Groups

As shown in Table 4, no significant difference in QV was observed for PTP, Bold, or Slim (2.2, 2.3, and 2.2, respectively; p < 0.05). Among participants aged ≥ 71 years, Bold tended to be easier to dispense, whereas among those aged ≥ 70 years, Slim tended to be easier; however, none of these differences reached the level of statistical significance (Table 7).

Table 7 Comparison of Quadratic Voting (QV) Between Age Groups

Comparison of NRS Across Different Age Groups

Table 8 shows a comparison of mean NRS scores between the ≤ 70 and ≥ 71 groups and the mean for all participants. Regarding the NRS for all participants, Bold was the highest (3.9). However, no significant difference was seen in the ≥ 71 group. In addition, Bold (3.8) and Slim (4.3) were higher than PTP (3.2) in the ≤ 70 group, and Slim was highest in ≤ 70 group.

Table 8 Comparison of Numeric Rating Scale (NRS) Scores Between Age Groups

Discussion

Considering the rapid aging of the global population,^34,35 problems associated with drug adherence are only expected to become more serious.^8,36–38 In addition, many people use over-the-counter drugs (OTC) and supplements in everyday life. The development of alternative methods that can help older adults take their medication could provide a stress-free way for users who struggle with this challenge.

This study analyzed alternative types of pill dispensers and conducted a comparison with PTP. As shown in Table 4, the average grip strength for all participants was 20.4 ± 7.5 kgf; however, six of the participants, all of whom had some level of impaired hand and finger function, had a grip strength < 15 kgf, which means that they tend to have some difficulties in handling their drug packaging in everyday life. Obviously, most such individuals require more time to dispense pills from PTP. One participant in the present study (No. 25) could not use PTP at all. Because she lives alone, she is always mindful of her drug taking and uses single-dose packaging. As shown in Figure 1, the Bold and Slim dispensers make repeat use easier. In addition, both types can be operated using only one hand and require little pinch or grip strength. Moreover, their simple instructions can be understood by any user.

Regarding the time needed to extract the pills, Bold had the shortest average time (Table 4). A comparison of average extraction times between two different age groups indicated that even when using the Bold type for the first time, extraction times were faster compared with PTP. Regarding the Slim type, although it was a little difficult for some older users in the ≥ 71 group to identify where to push on the packaging, those in the ≤ 70 group could use it appropriately, and thus had the fastest times; therefore, the Slim type could be used by all age groups.

No significant difference in average QV, which reflects user preferences, was observed among the three package types (Table 4). However, Bold was significantly higher than the other types in the ≥ 71 group, and Slim was the highest in the ≤ 70 group (Table 8). The older users in the ≥ 71 group may have preferred Bold because it can easily be used with one hand, regardless of grip or pinch strength, whereas those in the ≤ 70 group may have preferred Slim because of its ease of use and convenience.

Regarding the NRS, which reflects the usability of pill taking, no significant differences were observed; however, Bold had the highest score compared with the others (Table 4). Looking at different age groups, in the ≥ 71 group, no significant difference was seen among the three items. In the ≤ 70 group, Bold and Slim had higher scores than PTP (Table 7). These findings indicate that all of the participants rated the new types of dispensers higher than PTP, even though they were not previously familiar with them.

As shown in Table 5, correlations between PTP and Slim were found with grip and pinch strength and time. No relation was observed between Bold and strength, which indicates that even the participants with weak grip and pinch strength could use Bold. Regarding QV and NRS, no strong correlations were found. These results indicate that there were no significant differences in these measures. The differences in the results could have been due to individual differences in hand and finger strength. In fact, 57.6% of the participants had less than average grip strength, 42.3% less than average pinch strength, and 61.5% less than average two- and three-point pinch. In addition, most of the study participants had some type of functional disorder in terms of handling the dispenser, and about half had more serious difficulties (Table 4); therefore, many such individuals could have difficulties in handling packages because of weakness, which can affect opening status in various ways and necessitate some level of support.

In the present study, difficulties in extracting pills from packages/containers were observed. However, such difficulties are seldom noticed in society. Older patients who experience difficulties in taking various medications at several different time points every day, particularly essential medications such as those for diabetes and high blood pressure, poor drug adherence can lead to serious adverse outcomes.^39–41 In the area of rheumatology, even expensive drugs such as Janus Kinase inhibitors need to be taken punctually without skipping.⁴²

Although most prescription drugs in Japan are covered by a universal health care insurance system, poor adherence affects the results of therapy and wastes money; therefore, additional efforts are needed to reduce leftover drugs. If patients can use a preferred pill container, it could improve drug adherence. In addition, individuals have numerous opportunities to take OTC drugs, and convenient containers such as the Bold bottle-type dispenser could be even more useful in everyday life. As the pharmaceutical industry needs to consider safe and effective drug delivery in regard to drug packaging, some alternative containers such as those described in the present study could be beneficial for some users.

This study was limited by its small sample size. Larger studies with more patients are needed to validate the present results. In addition, it would be interesting to investigate patient preferences among a more diverse population of users, including healthy adults, in a wider variety of settings.

Conclusion

In the present study, we evaluated the usability and patient preferences associated with three types of drug packages/containers. We also measured the functional pinch and grip strength of the participants. Because daily medication use is the primary therapeutic method for patients, personal preferences for drug dispensers could be highly important for improving drug adherence. Although PTP is effective for many patients, alternative container types may improve usability for some patients. In addition, patient-preferred drug dispensers could improve adherence to OTC drugs and supplements.