By Ed Miseta, Chief Editor, Clinical Leader
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In early 2013, an initial groundbreaking survey was conducted to determine patient perspectives on investigational medicinal products (IMPs). The survey, sponsored by ISPE (International Society for Pharmaceutical Engineering), was intended to provide an international perspective on IMPs to ensure clinical supply packaging, labels, and booklet labels were patient-friendly.
Unfortunately, 97 percent of the 1,400 respondents were based in the U.S. Additional surveys were conducted in 2015 to garner a more global perspective and include more patients from the EU, China, and Japan.
Esther Sadler-Williams, global director of strategic development and innovation, clinical supply services for Catalent Pharma Solutions, did not want to have to go back to the funders of the original study to ask for more money to complete the EU survey. This necessitated coming up with a creative and inexpensive method of gathering additional data. In the EU, her group worked closely with the NIHR (National Institute for Health Research), which helped along with NHS Greater Glasgow and Clyde, to coordinate the effort with a U.K. network of clinical trial pharmacists.
“The NIHR was a good partner to have,” she states. “They worked very hard to grant us access to clinical sites, which then provided us with access to patients. Initially, we were not sure if that would allow us to cast a wide enough net, so we also partnered with EUPATI [European Patients’ Academy on Therapeutic Innovation], an organization that really supports patient advocacy groups to try and help them support the clinical trial process.”
While those networks gave the researchers the European connections they needed, the group still needed someone to analyze the EU results. That need was met via a partnership with the Biostatics Group of the University of Glasgow. With all of those European partners in place, Sadler-Williams felt it would be possible to pursue the EU survey without going back to underwriters for additional financial support.
The 2013 survey was edited and revised. Questions that provided relevant information were retained, while others were discarded. Other questions were added at the request of the partners. The new survey, which contained 48 questions, was then shared with the research teams in China and Japan.
“We all used the same survey because one of our goals was to be able to look at commonalities across the three regions,” says Sadler-Williams. “In Europe, the survey was available only in English. While the surveys were not exactly the same across all three regions, we did try our best to make them as consistent as possible.”
EXTRA EFFORT REQUIRED IN CHINA
Lynn Wang, regional lead of Asia Pacific Global Clinical Supply at Merck, headed up the survey in China. She notes a survey of this type, which looked at patient perceptions of clinical supplies, had never been conducted in China. With the number of clinical trials in China increasing during the last 10 years, she also felt the timing was good to take a look at the perspectives of both patients and sites regarding their clinical supplies.
“We took the survey that was prepared by Esther and her team in the EU, translated it into Chinese, and made it available in both paper and mobile versions,” says Wang. “This was very different from Europe, where all of the surveys were electronic. We felt that execution would be a primary issue for the patients and wanted to make it as easy as possible for them to complete it. We did have to make some small modifications to it in order to make it more tailored to China researchers and patients. In the U.S. and the EU, many patients may have been involved in clinical research for years, whereas in China, many would have been relatively new to the process.”
It was also felt that simply sending patients the paper or mobile survey would not be enough to garner a significant number of responses. In fact, the research team in China took the extra step of contacting participants individually. Questions were handed to the participants, who then had the questions and the intentions of the researchers explained to them. Volunteers also were asked to confirm that they understood the questions and the purpose of the survey.
Reaching out to potential participants was one of the biggest challenges, and various methods were used. Two of the most successful techniques involved community outreach under DIA (Drug Information Association) China and the five organizations that managed clinical sites. A total of 2,500 patient responses was received, with 1,935 containing valid responses. Those were used in the final analysis.
“In the EU, we knew we were at a bit of a disadvantage since the survey was going to be available only in English,” says Sadler-Williams. “But before we decided if additional work would have to be undertaken with EU translated versions, we still wanted to see what sort of response we could get and whether the results would be consistent with those obtained in 2013. Japan has initiated a patient survey, but there are a number of challenges in undertaking this type of survey there, so it may be many months before a response that is statistically evaluable can be completed in this region.”
SATISFACTION HIGH, BUT IMPROVEMENT OPPORTUNITIES EXIST
First, a recap of the results from the 2013 survey. As noted earlier, 97 percent of those surveys were from U.S. respondents. The survey found a high level of satisfaction with both clinical trial packaging and instructions and an acceptable level of reported compliance. Opportunities for improvement were noted in relation to medicine kit format preferences and kit differentiation, and it was felt new technology solutions could enhance dosing and visits via electronic reminders. Additionally, respondents felt kit design and labeling could play a stronger role in assisting patients with dosing information and proper product handling.
For the patients in Europe and China, one of the key questions on the survey dealt with how easy the clinical medicine kits were to use. The results were similar to the 2013 survey. About 90 percent of respondents found the kits easy or somewhat easy to use. However Sadler-Williams cautions the results should not make pharma complacent, thinking they don’t need to change anything. After all, there are still a lot of patients who feel that the kits could be easier to use. “[Not fully understanding the kits] could result in those patients being unable to comply with their dosing schedule,” she says. “To illustrate that even further, another question asked if the design of the kit supported the patients’ ability to take their medicine on schedule. On this question, the results from the EU and China were very different from the results in the U.S.”
Forty percent of respondents in the EU noted the kits helped them to take their medicines on schedule. It was slightly higher (46 percent) in China. However, both of those numbers were significantly less than the 60 percent figure noted in the U.S. So while the majority of patients found the kits easy, or somewhat easy, to use, many found the kit design did not help to remind them to take their medicine.
“I think that is a key takeaway for executives,” says Sadler-Williams. “There is an opportunity here to really think about the design of the kit, where possible, and get patient groups together in advance of the study. Present a template of the design and solicit feedback from them. Asking these questions of patients after the trial is too late. Any feedback they provide ahead of time can make the kits easier to use and perhaps improve patient retention.”
Wang notes that another key difference that surfaced between U.S./EU respondents and those in China had to do with how patients were notified of dosing instructions. In the EU, 81 percent of respondents (58 percent in the U.S.) indicated dosing instructions on the label would help them to take their medicine on schedule. Another 68 percent noted dosing units on the container would help. In China, only 55 percent felt dosing instructions on the label would help. A significant majority of respondents (77 percent) indicated they would prefer verbal instructions from their physician/nurse/pharmacist on every visit.
“Patients in China clearly prefer that personal communication,” says Wang. “Having the information on the label to refer back to is important to patients, but there is still a strong preference for actually hearing those verbal instructions on how and when to take the medicines from the site staff. They enjoyed getting the kit and reading the instructions, but they still wanted to talk to somebody and have it verbally explained to them. That investigator’s message is both important and effective.”
KIT SIZE AND STORAGE WERE NOT AN ISSUE
Since patients generally have to move and store the kits containing their medicines, you might expect the size of the kits and the ability to properly store them to be important issues for patients. Surprisingly, that was not the case with most patients. In the U.S. study, 77 percent indicated the size of the kits was about right, and 82 percent noted they were easy to store. Similar results came out in the EU and China studies as well.
“Storing the kits wasn’t a particular problem to any of the survey participants,” notes Sadler-Williams. “Significant majorities in both the EU and China indicated kits were the right size and they were easy, or very easy, to store. When asked what characteristics about the kit were important to them, size and weight (along with single doses) were perceived to be less important, while clear instructions, ease of use, and label information again garnered high marks. Ease of transport was also cited as being a concern.”
The researchers were concerned not just about preferences today, but also what they might be in the future. One question asked how patients would prefer to receive information going forward. Here, the responses seemed to vary by region. In the U.S., the top three choices, in order, were text message, smartphone app, and website. In the EU, the order of preference was email, text, and smartphone. In China, the preferred methods were text message, regular mail, and smartphone. The least-preferred method in all three regions was electronic reader.
“This obviously has a lot to do with culture,” states Wang. “When you look at the responses from China, two-thirds came from current patients, who were already participating in a clinical trial. The age group also ranged from 54 to 65. This might explain the reluctance to receive messages via email and eReaders (the bottom two choices), but those preferences may change over time.”
A PREFERENCE FOR HOME DELIVERY AND RETURNING MEDICINES
A few additional findings are worth noting. Respondents in both the EU and China (approximately 14 percent) indicated they would keep unused medications for future use. In China, only 2 percent of patients said they did not return the used/unused medicines, and 6 percent indicated they would do so occasionally, which is less than that in the U.S. and EU.
Patients were also asked about their preference for having their clinical medicine supplies delivered to their homes, as opposed to having to pick them up at a clinic. In the EU, 71 percent of respondents indicated it would be helpful. In China, 78 percent indicated that option would be very, or somewhat, helpful. While this was expected in older age groups, it was also evident in the younger age groups where patients might have jobs, families, and more active lifestyles.
"Having the information on the label to refer back to is important to patients, but there is still a strong preference for actually hearing …. verbal instructions."
Regional lead of Asia Pacific Global Clinical Supply, Merck
“If even a few patients keep their clinical medicines for future use, that is a concern,” says Sadler-Williams. “As an industry designing these studies, we need to ensure processes are put in place for sites and patients to understand that all unused medicines are to be returned to the site. Sponsors and sites really need to work harder to make sure all of these medicines are properly returned.”
Respondents were also asked about the effectiveness of product labels and pictograms. In the EU, most respondents report having read the booklet label at least once, and most noted it was easy to view and was large enough to read. Ninety-six percent correctly identified the four pictograms that were included. For future use, 51 percent said they would prefer just the text, 8 percent would prefer just the pictogram, and 41 percent would like to see both.
Finally, Sadler-Williams and Wang both recommend that sponsors consider regional differences when designing trials. Even small differences in preference across regions can impact trial results. For example, patients in the U.S. and China have a strong preference for receiving their medicines in bottles, whereas patients in the EU prefer blister packs.
“In large, global studies, we are often tempted to make and manage everything exactly the same,” says Sadler-Williams. “This can make things much easier to manage. But what is more important is the preference of the patient. Taking those concerns into account is vital to ensuring the overall success of the trial.”