Facilitators and barriers to spinal cord injury (SCI ...

Journal of Neurotrauma Facilitators and barriers to spinal cord injury (SCI) clinical trial participation: Multi-national perspective of people living with SCI (doi: 10.1089/neu.2015.4064) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

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1 Facilitators and barriers to spinal cord injury (SCI) clinical trial participation: Multinational perspective of people living with SCI

Running title: Facilitators/barriers to SCI trial participation

Authors: Kim D. Anderson1, Rachel E. Cowan1, Jane Horsewell2 1

University of Miami Miller School of Medicine, Department of Neurological Surgery,

Miami Project to Cure Paralysis. 2

The European Spinal Cord Injury Federation, Kantonstrasse 40, CH 6207, Nottwil

Corresponding author: Kim. D. Anderson, Ph.D. Associate Professor, Department of Neurological Surgery, Director of Education, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Lois Pope Life Center Room 1-31, Mail Locator R-48, Miami, FL 33136. Email. [email protected] Ph. 305-243-7108; Fax. 305-243-3913 Other authors: Rachel E. Cowan, Ph.D. Assistant Professor, Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Lois Pope Life Center Room 1-49, Mail Locator R-48, Miami, FL 33136. Email. [email protected] Ph. 305-243-1949; Fax. 305-243-3913 Jane Horsewell, M.Sc. President, The European Spinal Cord Injury Federation, Kantonstrasse 40, CH 6207, Nottwil, Switzerland Email. [email protected] Ph. 0045 3961 6131 Fax. +41 (0)41 939 54 39

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2 Abstract These are exciting times for the translation of promising interventions for spinal cord injury (SCI) into testing with clinical trials. These interventions include acute surgical decompression, neuroprotection, neural repair, cell replacement, activity-based rehabilitation, and medical devices, including devices requiring surgical implantation. By nature, clinical trials can have very strict inclusion and exclusion criteria which narrow down the pool of potential participants. Meeting enrollment numbers for properly powered trials is a daunting task. Therefore, it is important that trials are designed in a manner that facilitates participation. The purpose of this research study was to learn more about the factors that encourage or interfere with the decision to participate in clinical trials from the perspective of people living with SCI. A multi-national survey was conducted, primarily on-line, in which 802 participants with SCI ranked 32 factors as facilitators or barriers using a Likert-type scale. There were 13 universal facilitators, 5 universal barriers, and 3 universally neutral factors. The number one facilitator was possible improvement in functionality and the number one barrier was possible decline in functionality – as may be expected. However, many unexpected facilitators and barriers were identified. There were also certain factors that were strong barriers or facilitators to certain sub-groups of people living with SCI. All of these factors should be taken into careful consideration when designing clinical trials so as to promote enrollment and enable adherence to different protocols.

Keywords: spinal cord injury; clinical trial; facilitator; barrier; participation

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Journal of Neurotrauma Facilitators and barriers to spinal cord injury (SCI) clinical trial participation: Multi-national perspective of people living with SCI (doi: 10.1089/neu.2015.4064) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. Page 3 of 29

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4 Introduction The field of spinal cord injury (SCI) research is clearly advancing in its identification of potential therapeutics for translation into testing with clinical trials. These interventions include acute surgical decompression, neuroprotection, neural repair, cell replacement, activity-based rehabilitation, and medical devices, including devices requiring surgical implantation such as epidural stimulation and brain machine/computer interface. There are currently several phase I clinical trials ongoing, an increasing number of phase II trials are beginning, and there will be multiple phase II and III trials in the near future (see summary tables hosted on the SCOPE website regarding current SCI interventional clinical trials http://www.scope-sci.org/trials.php ).

These trials will require large

numbers of participants and will likely require multi-national collaborations. By nature, clinical trials can have very strict inclusion and exclusion criteria, which narrow down the pool of potential participants. Meeting enrollment numbers for properly powered trials is a daunting yet critical task. Therefore, it is important that the field design these trials in a manner that facilitates participation.

Recruitment and enrollment for clinical trial participation can be impacted by many factors, as highlighted throughout the literature across diseases. Some of these factors may be less amenable to change due to the research question, such as inclusion/exclusion criteria, and other factors may be dependent upon financial resources, such as the number of trial sites that can be funded. However, once appropriately qualified individuals are identified, there is no guarantee that they will decide to participate in a trial(s). There has been some study of factors that influence the choice to participate from the perspective of

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5 individuals living with cancer, the older adult population, and individuals living with sickle cell anemia1-4. In cancer, for example, barriers to participation that have been identified from potential participants include the understanding of randomization, assignment to placebo or treatment, possible adverse effects, unease with research, complex protocols, financial burden, transportation logistics, and trust in physicians.1 In the older adult population, for example, barriers to participation in interventional trials include understanding complex documents (e.g. overly complex consent forms), distrust of research, transportation, lack of understanding of the study protocol, concern about excessive intrusiveness, and family members acting as gatekeepers/proxies.2,3 In sickle cell anemia, for example, barriers to participation include general mistrust of research, emotional and practical concerns, the possibility of randomization, and unknown longterm risks; facilitators include more education, specifically peer education and improved education in study rationale.4

We chose barriers that are common across the three

populations for which there is literature, to be evaluated in the current study to determine if they are common in the SCI population as well.

To design clinical trials targeting SCI in a manner that facilitates participation, it is important to obtain information from the perspective of potential participants, i.e. people living with SCI. One method of obtaining information from large numbers of people is to do a survey. The Internet has become a useful tool by which to conduct research (Walker 2013). Online research methods have many potential benefits, including the possibility of increasing the geographical span as well as inclusion of individuals with mobility or communication difficulties (Walker 2013). Previous studies show that people with SCI

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6 prefer to receive research information over the Internet5 and important scientific information can be gained from Internet-based research survey to guide research priorities.6-9

A survey was developed targeting a multi-national population of individuals living with SCI to determine whether a host of factors, drawn from the literature, were viewed as facilitators or barriers to making a decision to participate in an interventional clinical trial.

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7 Materials and Methods Survey design A questionnaire was used to acquire information about facilitators and barriers to the decision to participate in interventional clinical trials from persons living with SCI worldwide. The questionnaire was divided into two sections: (1) factors related to clinical trials and (2) demographics. Thirty-two factors related to interventional clinical trials were presented with the instructions to rate whether each would encourage (facilitate) or discourage (be a barrier) participation. A Likert-style rating scale was used from -3 to +3 (-3 strong barrier, -2 intermediate barrier, -1 weak barrier, 0 neither a barrier nor facilitator, +1 weak facilitator, +2 intermediate facilitator, +3 strong facilitator). This was followed by 7 basic demographic questions. The survey was purposefully kept short to encourage participation from a large number of individuals.

The questionnaire was administered online using the software program SurveyMonkey™. A detailed description of SurveyMonkey™ security features is available at www.surveymonkey.com/mp/policy/security/. All answers/data were immediately stored in a secured, computerized database. In an effort to not exclude individuals who did not have access to the Internet, the option of completing the survey via the postal mail or by telephone was provided; answers were immediately entered into the online survey upon receipt.

All survey questions and answer choices are available in the Supplementary Material. The study was reviewed and approved by the University of Miami (UM) Institutional

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8 Review Board (IRB).

We certify that all applicable institutional and governmental

regulations concerning the ethical use of human volunteers were followed during the course of this research.

Participant recruitment To qualify for the study, individuals had to have a spinal injury and be 18 years of age or older (obtained via self-report). A waiver of signed consent was granted by the UM IRB. All of the elements of informed consent were described on the study information page, which was displayed on the first page of the survey. Consent and qualification were inferred by agreement and further participation in the survey. Those individuals that did not agree to the information provided on the study information page elected to not complete the survey. The survey link was emailed directly to 1,900 individuals living with SCI.

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9 Participants were recruited by word of mouth through people with spinal cord injuries, postings on the world wide web, support groups, and multiple consumer organizations, such as The Global SCI Consumer Network, The European Spinal Cord Injury Federation (ESCIF), United Spinal Association (USA), Rick Hansen Institute (RHI), The Miami Project (TMP), Spinal Cord Injury Network (SCIN), Australian Quadriplegic Association of Victoria (AQA Victoria), Disability Wellnes Center, New Zealand Spinal Trust, Spinal Cord Injuries Association of Turkey (TOFD), Nina Foundation, and Sri Lanka group. Enrollment occurred between March and August 2014.

Data reporting and analyses Current age and injury duration groups were reported based on the international SCI basic data set recommendations.10 For reporting of sample demographics we followed the International SCI Core Data Set recommendations.11 Geographical macroregion groupings for Asia & Africa, Canada, Europe (includes the United Kingdom), Latin America & Caribbean, Oceania, and United States (US) were drawn from the United Nations (UN) Statistics Division (http://unstats.un.org/unsd/methods/m49/m49regin.htm ). For each of the 32 factors, participant responses were analyzed to determine the majority perception. For a response to be considered the majority perception, it had to have a prevalence of at least 50% as a barrier (across -3, -2, -1), facilitator (across +3, +2, +1), or neutral (represented as 0). When a majority perception did not exist, the factor was considered divided. Data were analyzed based on gender, current age group, injury level, injury duration group, and geographical regions described above.

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10 Results Demographics A total of 802 participants rated all 32 factors (this represents an estimated 42% response rate base on the information available); however, 33 of those respondents did not provide answers to the demographic questions so the analyses presented here are for the 769 participants who completed the entire survey. The population was 66% male and 50% tetraplegic (15% cervical 1-4, 35% cervical 5-8, 50% thoracic 1 – sacral 5). The mean age of the population was 48±13 years (standard deviation). The primary cause of injury was transport-related (42%), followed by sports (17%), falls (14%), non-traumatic (13%), other traumatic (8%), assault (5%), and unknown (2%) [these categories were used per the International SCI Core Data Set].11 The mean post-injury duration was 16±12 years (standard deviation), with a distribution of 0.3% 20 years [these categories were used for reporting based on the international SCI basic data set recommendations].10 The distribution of participants from macro-geographical world regions was: Asia & Africa 4%, Canada 13%, Europe & United Kingdom 13%, Latin America & Caribbean 3%, Oceania 11%, and US 56%.

Factors that are universally facilitators, barriers, or neutral As described in the methods section, a factor was considered to be universal if at least 50% of the respondents in at least 15 of the 17 sub-groups analyzed rated it as a facilitator, barrier, or neutral (for a full reporting of results for all 17 sub-groups analyzed, see Supplementary Table 1). There were 13 factors that fit the criteria of being rated as a

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11 universal facilitator (Figure 1A).

The highest rated facilitators were possible

improvement in functionality (91%), better understanding of your SCI (86%), opportunity to help future people with SCI even if you do not experience improvement (altruism, 85%), access to cutting edge care (85%), opportunity to learn more about your health (85%), wish to be more independent (83%), and opportunity to receive free (extra) medical tests or treatment (77%). There were 6 other universal facilitators that were rated between 50-80% (Fig. 1). There were 5 factors that were rated as universal barriers to clinical trial participation (Figure 1B). The highest rated barriers were possible decline in functionality (80%), possible side effects (70%), and possible out-of-pocket expenses (64%). There were only 3 factors that met the criteria of being universally neutral (Figure 1C); these were religious issues (71%), prior experience with clinical trials (66%), and privacy issues (63%).

Factors that were divided The remaining 11 factors evoked divided responses that overall were not strong facilitators or barriers (Figure 2). One of the divided factors, knowledge about clinical trials, trended towards being a facilitator with 89% of respondents considering it to be neutral or a facilitator. Figure 3 shows the variety of responses regarding these 11 factors from the 17 subgroups analyzed. More than 50% of the Latin America & Caribbean, Oceania, and Asian subgroups rated this as a facilitator (Fig. 1A.1). Five other factors trended towards being barriers (Fig. 3A.2-6). Transportation to/from the research facility (Fig. 3A.4) was a clear barrier for the Asian and Canadian subgroups, 11-20 and >20 years post-injury subgroups, 46-60 years age subgroup, and female subgroup. Family

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12 obligations (Fig. 3A.3) was rated as a barrier by 52% of the Latin America & Caribbean subgroup. The final 5 factors had no clear trend towards being either a facilitator or a barrier (Fig. 3B.1-5). Interestingly, all 17 subgroups were near equally divided on how they rated being a “guinea pig” (Fig. 3B.1) and possibility of being in the “control group” (Fig. 3B.3). Possible impact on caregiver/attendant/assistant was close to being scored as universally neutral, with 14 of 17 subgroups viewing it as neutral (Fig. 3B.5).

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13 Discussion A multi-national survey was conducted in which a large sample of individuals living with SCI, primarily chronic injury, ranked 32 factors as facilitators or barriers to their decision making process regarding participation in interventional clinical trials. There were 13 universal facilitators, 5 universal barriers, and 3 universally neutral factors.

Some of the high ranking universal facilitators were factors that one would intuitively think would be important when making a decision about clinical trial participation, such as the possible improvement in functionality and wish to be more independent, which are both related to the ultimate goal of the intervention being efficacious. However, when efficacy is unknown, for example with Phase I trials, or when a control group is required, for example in Phase II and III trials, there are other unexpected factors that can strongly facilitate participation. These include the opportunity to learn more about your general health and to better understand your SCI, recommendation from SCI peers, and the simple desire to participate in something that maintains hope. These are factors that could easily be taken into consideration during the design of trials by creating educational feedback opportunities to participants as well as engaging other individuals living with SCI to be team members.

Similarly, some of the universal barriers were factors to be expected, such as the possibility of adverse effects and possible decline in function, which are strongly considered when weighing the risk versus benefit probabilities of translating an intervention.

However, many barriers were identified that are not related to

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14 physical/medical risks, specifically the possibility of out-of-pocket expenses, concern about losing medical coverage, and concern about losing income. It is true that research procedures in a clinical trial are not charged to the participant. However, if travel is required and not paid for by the research team, it is an out-of-pocket expense; if an attendant is needed to assist with completion of certain tasks for the trial and the cost is not paid for by the research team, it is an out-of-pocket expense. Medical coverage or disability income is often tied to certain definitions of disability (for the US, see the Social

Security

Advisory

Board

definition

of

disability

http://www.ssab.gov/documents/socialsecuritydefinitionofdisability.pdf ).

There is a

legitimate fear that participating in a clinical trial could improve function enough to disqualify the person from maintaining their medical coverage or disability income, yet not improve function to the degree that those supplements are no longer needed. Similarly, a concern for those individuals that are already working and bringing in a steady income is that the time commitment of participating in a clinical trial may be so onerous that it may negatively impact their work and cause them to lose essential income. All of these factors should be taken into careful and active consideration when designing clinical trials so as to promote enrollment, reduce participant burden, and enable adherence to different protocols.

There were also certain factors that were stronger barriers or facilitators for certain subgroups of people living with SCI, see Figure 3. There may be a need to tailor design based on “geographic” region, taking into account sociocultural sensitivities.

For

example, survey participants in Latin America and the Caribbean rated family obligations

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15 and possible impact on family/friends as barriers. It would be important to understand more about these concerns, for example, do individuals with SCI living in these countries rely more heavily on family and friends for their care and income? If so, then it would be critically important to design protocols that do not overly burden the family. Transportation to/from the research facility was a barrier for multiple sub-groups (see Fig. 3A.4). This can be addressed in multiple ways in protocol design, for example 1) reimburse transportation costs, 2) provide actual transportation, 3) reduce the number of visits to the research facility, and/or 4) use more telemonitoring. Minimizing the time commitment can also reduce the impact on work and family obligations, thus reducing multiple barriers.

Ultimately, when designing clinical trial protocols a balance has to be made between obtaining the most data possible and actually being able to complete the trial. If a trial is designed in a manner that generates too many barriers, people either will not participate or they will enroll and then drop out – neither of which enables translation. The data presented here have identified multiple barriers that can be removed or lessened and multiple facilitators that can be enhanced in relatively easy ways. One has to be careful, however, that facilitators are not used to the extent that they become coercive. In the end, there is still risk of functional loss and adverse effects when testing experimental interventions and potential participants need to be made aware of the risks that may be involved.

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16 Consumer engagement has been largely untapped in the SCI clinical trial realm. In the cancer literature there is a strong push for participant advocates, peer mentors, and participant navigators to enhance clinical trial recruitment and retention.1 The survey results presented here demonstrate that recommendations from SCI peers is a very strong facilitator. Additionally, approaches used in community-based participatory research are recommended by the cancer field as well, such as the inclusion of community stakeholders in trial design.1 Results from the current survey can be used as a first step in engaging SCI consumers in protocol design. Community physicians (e.g. physicians who care for people living with SCI who do not have expertise in SCI medicine, or physicians who are not associated with academic medical centers) are also stakeholders who should be engaged.1 They can be valuable sources of referral to clinical trial investigators and, based on the data presented here, they can facilitate the decision of individuals with SCI to participate (see Fig. 1B.4). This could also be a barrier, however, if community physicians are unaware of clinical trials for SCI or have a negative viewpoint. Improved education or awareness of this referral source could be an activity taken on by SCI professional organizations.

A recent systematic review of the literature demonstrates that participant engagement in various types of healthcare research is highly feasible, can be conducted in many different settings, and via a variety of methods.12

It has been shown to increase

enrollment, help secure funding (note the new and growing Patient Centered Outcomes Research Institute funded by the US government, which is heavily focused on engagement), aid in study design, and, of particular importance, to help improve the

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17 choice of relevant outcome measures. There can be challenges, of course, the most commonly cited ones being the extra time and funding needed for engagement and the worry that “engagement” reflects a token commitment.12

Limitations We acknowledge the limitations of this survey; it was only conducted in English and was administered primarily on-line. Our sample could therefore be biased towards persons who frequent the internet and who understand English. We did purposefully keep the survey short in an effort to make it less cumbersome and burdensome to participants. It is impossible to know how many additional individuals saw the survey link due to the wide array of internet-based recruitment outlets and consumer organizations.

The

questions and statements were also vetted and edited by individuals in the United States, Europe, Canada, and Australia prior to being finalized. However, these countries are in developed regions of the world and the language may therefore have been biased towards individuals with a higher education and socioeconomic status. Despite this, there was some feedback from individuals for whom English was their second language regarding the interpretation of some questions. Additionally, by far majority the individuals that participated in the survey were one or more year’s post-injury. This could have been due to many factors, such as newly injured individuals still being in the hospital and/or not yet integrated into the community, therefore not accessible via the recruitment methods used here; or learning about the survey and choosing not to participate. Facilitators and barriers to clinical trial participation may be different in the acute and subacute time

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18 period and that information would likely need to be obtained in a different format, such as in-person interviews.

Conclusion The value of creating a mutually respected partnership between SCI consumers and researchers to better inform and enable successful clinical trials is well worth any challenges that may need to be overcome. The data presented here provide one avenue by which we can begin to think about changing small, but significant, aspects in clinical trial design that could have an amplified effect on trial success.

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19 Acknowledgements The authors would like to thank the partners of this project: Global SCI Consumer Network; Rick Hansen Institute; Institute for Safety, Compensation, and Recovery Research; Ontario Neurotrauma Foundation. Importantly, the authors would like to thank all the individuals living with SCI around the world who took the time to provide input to this study.

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Author Disclosure Statement

No competing financial interests exist.

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21 References 1. Denicoff AM, McCaskill-Stevens W, Grubbs SS, Bruinooge SS, Comis RL, Devine P, Dilts DM, Duff ME, Ford JG, Joffe S, Schapira L, Weinfurt KP, Michaels M, Raghavan D, Richmond ES, Zon R, Albrecht TL, Bookman MA, Dowlati A, Enos RA, Fouad MN, Good M, Hicks WJ, Loehrer PJ Sr, Lyss AP, Wolff SN, Wujcik DM, Meropol NJ (2013) The National Cancer InstituteAmerican Society of Clinical Oncology Cancer Trial Accrual Symposium: summary and recommendations. J. Oncol. Pract. 9:267-276. 2. Knechel NA (2013) The challenges of enrolling older adults into intervention studies. Yale J Biol Med. 86:41-47. 3. Denson AC, Mahipal A (2014) Participation of the elderly population in clinical trials: barriers and solutions. Cancer Control. 21:209-214. 4. Lebensburger JD, Sidonio RF, Debaun MR, Safford MM, Howard TH, Scarinci IC (2013) Exploring barriers and facilitators to clinical trial enrollment in the context of sickle cell anemia and hydroxyurea. Pediatr Blood Cancer. 60:13331337. 5. Edwards, L, Krassioukov, A, Fehlings, M (2002) Importance of access to research information among individuals with spinal cord injury: results of an evidencebased questionnaire. Spinal Cord. 40:529-535. 6. Anderson, KD (2004) Targeting recovery: Priorities of the spinal cord injured population. J. Neurotrauma. 21:1371-1383.

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22 7. Anderson, KD, Borisoff, JF, Johnson, RD, Stiens, SA, Elliott, SL (2007) The impact of spinal cord injury on sexual function: concerns of the general population. Spinal Cord 45:328-337. 8. Anderson, KD, Fridén, J, Lieber, RL (2009) Acceptable benefits and risks associated with surgically improving arm function in individuals living with cervical spinal cord injury. Spinal Cord. 47:334-338. 9. Cowan RE, Nash MS, Anderson KD (2013) Exercise participation barrier prevalence and association with exercise participation status in individuals with spinal cord injury. Spinal Cord. 51(1):27-32 10. DeVivo MJ, Biering-Sørensen F, New P, Chen Y (2011) Standardization of data analysis and reporting of results from the International Spinal Cord Injury Core Data Set. Spinal Cord. 45:596-599. 11. DeVivo M, Biering-Sørensen F, Charlifue S, Noonan V, Post M, Stripling T, Wing P (2006) International Spinal Cord Injury Core Data Set. Spinal Cord. 44:535-540. 12. Domecq JP, Prutsky G, Elraiyah T, Wang Z, Nabhan M, Shippee N, Brito JP, Boehmer K, Hasan R, Firwana B, Erwin P, Eton D, Sloan J, Montori V, Asi N, Dabrh AM, Murad MH (2014) Patient engagement in research: a systematic review. BMX Health Serv. Res. 14:89-97.

Figure Legends

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Figure 1. Universal Factors. A) Factors that were rated as universal facilitators by at

least 15 of the 17 subgroups analyzed. B) Factors that were rated as universally neutral

by at least 15 of the 17 subgroups analyzed. C) Factors that were rated as universal

barriers by at least 15 of the 17 subgroups analyzed.

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Figure 2. Factors that yielded divided responses.

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26 Figure 3. Divided Factors. A) Factors that were divided in response, but demonstrated a majority trend towards being either neutral or a facilitator (3A.1) or neutral or a barrier (3A.2-6). B) Factors that were divided with no clear trends. For all, rows are factors, columns are participant subgroups. In each row, blue indicates the percentage of the subgroup who rated the factor a facilitator (+1 to +3); beige indicates the percentage who rated the factor neutral (0); red indicates the percentage of the subgroup who rated the factor a barrier (-1 to -3). For any subgroup where there was a majority perception, we identified that by overlaying it with the actual percentage.

STUDY INFORMATION AND CONFIDENTIALITY The purpose of this research study is to learn more about the things that encourage or interfere with the choice to participate in clinical trials from the perspective of people living with spinal cord injury (SCI). There are many different types of clinical research. Clinical trials are a specific sub-type of clinical research; this survey is a different sub-type of clinical research. By definition, a clinical trial is a medical or behavioral research study of human beings that is designed to answer specific questions about medical or behavioral interventions (such as new cells, drugs, devices, therapies or new ways of using known cells, drugs, devices, therapies). Clinical trials are used to determine whether the interventions being tested are safe and effective. If so, they can then become part of standard medical care. The information gained from this study will provide valuable information to scientists who design and perform clinical trials for SCI. There will be an increasing number of clinical trials in the near future testing interventions for SCI and that will require more people with SCI to agree to become research participants. Sometimes clinical trials are designed in ways that interfere too much with everyday life. By sharing your opinions with these scientists you are providing vital information that will contribute to the design of clinical trials that are easier for more people with SCI to participate in. Your voice can make a difference! Dr. Kim Anderson, the Principal Investigator for this study, also has a spinal cord injury herself and she is trying to bridge the gap in communication between scientists and the community living with SCI. This study involves a questionnaire that takes about 10 minutes to complete. To participate in this study you must have a spinal cord injury and be over the age of 18. Your name and preferred contact information will be collected with the survey so that we may re-contact you in the future if other questions come up about clinical trial design. However, your name and contact information will be unlinked from your answers to protect your confidentiality. Dr. Anderson will be the only person with access to your personally identifying information.

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You may not benefit directly from participating in this research study and you have the alternative not to participate in this research study. Your participation is voluntary. You can decline to participate or can stop participation at any time, if you wish to do so, without any negative consequences to you, however if you stop the survey before completion your answers will not be saved. If you participate in this research study you will be entered into a drawing. At the end of the data collection phase, three participants will be randomly selected to receive compensation equivalent to $25 US Dollars. If you have questions or concerns, you can contact Dr. Kim Anderson at 305-243-7108 or [email protected] . If you have questions regarding your rights as a research participant, contact the University of Miami, Human Subject Research Office at 305-243-3195. By beginning the survey, you are confirming that you meet these requirements and are willing to participate in this study.

Study the list of factors below. Would they discourage you from participating in a clinical trial (i.e. act as a barrier) or would they encourage you to take part (i.e. act as a facilitator)? Rate each factor from -3 to +3 as follows -3 strong barrier -2 intermediate barrier -1 weak barrier 0 neither a barrier nor facilitator +1 weak facilitator +2 intermediate facilitator +3 strong facilitator Factors

-3

-2

-1

0

+1

+2

+3

Being a “guinea pig” Not knowing if your condition will improve Possible improvement in your functionality Possible decline in your functionality Possible side effects Wish to be more independent Possibility of being in the “control group” (not receiving the active intervention) Religious issues Privacy issues Possible out-of-pocket expenses Time commitment

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28 Concern about losing medical coverage/access to medical care Concern about losing your income Transportation to/from the research facility Work obligations Family obligations Family support and encouragement Possible impact on family or friends Possible impact on caregiver/attendant/assistant Require help to perform what is required in the trial Experience with previous clinical trials Knowledge about clinical trials Recommendation from your doctor Recommendation from other people with SCI Recommendation from SCI consumer organizations Opportunity to help future people with SCI even if you do not experience improvement Opportunity to learn more about your general health Opportunity to receive free (extra) medical tests or treatments Possibility to earn a small amount of extra money, if offered Need to retain a positive attitude “Never give up hope!” Access to cutting edge care Better understanding of your SCI 1) Gender – circle 1 Male Female 2) What country were you born in? – write in your answer ________________________ 3) What country do you currently live in? – write in your answer ________________________ 4) How old are you? – write in your answer .______________years 5) What caused your spinal cord injury? – circle 1 Sports (any type of sporting activity, including diving, surfing, etc.) Assault (gunshot, stab wound, hit with blunt object, explosion, etc) Transport (car, truck, ATV, motorcycle, bicycle, boat, aircraft, etc.) Fall (from height or level ground, trip over an object, slipping on wet surface, etc.) Other traumatic cause- ___________________________________________________ Non-traumatic spinal cord dysfunction (birth disorder, infection, tumor, transverse myelitis, spinal stroke, etc)

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29 Unknown 6) Where is your spinal cord injured? – circle 1 Cervical 1-4 (upper neck) Cervical 5-8 (lower neck) Thoracic 1-6 (upper back) Thoracic 7-12 (mid back) Lumbar 1-5 (lower back) Sacral 1-5 (tail bone area/cauda equina/conus medullaris) 7) Year of injury – write in your answer ______________ 8) What is your name? First_______________________ Last/Surname_________________________________ 9) What is your email address, if you have one? _______________________________________________________________________ 10) What is your mailing/post address? _______________________________________________________________________

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Journal of Neurotrauma litators and barriers to spinal cord injury (SCI) clinical trial participation: Multi-national perspective of people living with SCI (doi: 10.1089/neu.2015.4 as been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ fro

Q1

Q2

Q3

Q4

Q5

Q6

Q7

Q8

Q9

Q10

Q11

Q12

Q13

F N B F N B F N B F N B F N B F N B F N B F N B F N B F N B F N B F N B F N B

Gender M F 37 27 39 40 25 33 31 24 47 42 22 34 90 94 5 3 5 2 8 6 14 9 77 85 12 6 21 17 67 78 82 87 16 11 2 2 23 18 43 42 34 40 12 8 70 74 18 18 16 12 63 63 21 25 13 11 26 20 61 69 23 13 39 43 38 44 15 10 31 32 54 58 13 10 34 39 53 51

18 -30 41 38 21 29 39 32 90 4 6 9 18 73 18 24 58 82 13 4 30 36 34 13 71 16 20 61 19 16 27 58 23 43 33 23 26 51 21 28 51

Age group 31-45 46-60 28 33 38 39 34 28 25 29 45 48 30 23 95 90 4 5 2 4 5 8 9 13 86 79 5 11 20 19 75 70 85 82 14 16 1 2 17 21 44 42 39 37 7 11 76 69 17 20 11 13 66 62 23 25 12 12 22 22 66 66 15 20 38 41 47 39 10 13 31 31 59 55 9 11 31 37 59 51

>60 39 41 19 36 39 25 91 4 5 10 13 76 12 16 72 87 10 3 22 47 30 16 67 17 21 61 19 12 29 59 25 40 35 10 36 53 13 44 44

Injury TP PP 34 33 38 40 28 27 27 31 46 44 27 26 92 91 4 5 4 4 6 9 13 13 82 78 8 12 19 20 72 69 88 80 10 18 2 2 18 24 45 41 38 35 9 13 72 71 19 16 12 18 67 59 22 23 11 14 23 24 66 62 17 22 41 40 42 38 12 14 32 31 56 54 12 13 38 34 54 51

Injury duration 0-10 11-20 >20 37 28 34 39 39 39 24 33 28 33 28 24 42 46 49 25 27 27 92 92 90 3 5 7 5 3 3 8 9 6 16 11 10 76 81 84 11 13 7 25 15 16 64 73 77 86 83 82 11 15 17 2 2 1 25 17 19 39 45 47 36 38 34 12 11 10 72 71 69 16 17 21 15 14 15 66 60 61 18 26 25 13 11 13 29 18 22 58 70 66 22 19 16 45 37 37 33 44 46 17 11 10 31 32 32 52 58 58 15 12 8 34 34 38 50 54 53

USA 34 40 26 31 46 23 91 5 4 6 12 82 9 19 72 83 15 2 18 46 36 11 70 19 15 62 24 12 24 65 17 42 41 11 32 58 10 36 53

Europe 34 38 28 26 51 23 95 1 4 9 11 80 14 17 69 92 8 0 26 38 36 14 76 11 12 75 14 16 22 62 21 35 44 20 28 52 15 35 51

Region of residence Canada ASIA 31 29 35 42 35 29 19 38 46 42 36 21 89 92 5 8 6 0 7 8 12 4 81 88 9 4 19 13 72 83 80 88 16 13 4 0 22 21 41 46 38 33 10 4 72 83 18 13 19 13 64 58 17 29 14 17 21 29 65 54 17 25 40 50 44 25 16 13 31 42 53 46 14 17 35 33 51 50

Oceania 37 40 23 30 33 37 93 6 1 11 22 67 14 28 58 82 16 2 30 36 34 12 69 19 16 61 23 11 29 60 30 37 33 12 36 52 16 36 48

LAC 30 42 27 24 45 30 91 3 6 9 12 79 15 12 73 91 9 0 18 39 42 12 67 21 12 48 39 12 21 67 27 36 36 21 18 61 15 27 58


Q14

Q15

Q16

Q17

Q18

Q19

Q20

Q21

Q22

Q23

Q24

Q25

Q26 Q27

F N B F N B F N B F N B F N B F N B F N B F N B F N B F N B F N B F N B F N B F N

19 34 47 15 46 39 16 49 35 59 30 10 28 42 30 18 55 26 23 48 30 24 65 10 44 46 10 59 34 7 66 28 6 56 37 6 87 9 4 85 12

19 31 50 9 55 36 11 52 37 53 34 13 26 45 29 17 52 31 16 47 37 20 66 13 44 45 11 60 35 5 69 25 5 64 30 6 84 10 5 85 13

26 31 43 21 36 43 20 47 33 60 22 18 39 34 27 23 49 28 23 41 36 17 74 9 47 42 11 60 32 8 67 22 11 58 32 10 88 6 7 84 12

18 35 47 10 45 45 13 47 40 58 32 10 26 45 29 17 55 27 17 50 33 21 66 13 42 46 12 59 37 4 70 27 3 59 36 4 85 10 5 85 14

18 30 51 12 50 38 15 51 35 58 31 10 27 42 31 16 56 28 21 47 32 24 64 12 46 44 10 60 34 7 67 28 5 59 35 6 85 11 4 86 12

16 38 47 15 61 24 13 55 32 53 37 10 23 49 28 20 52 28 21 50 28 28 63 9 41 51 8 59 33 9 64 28 7 59 33 8 88 8 4 85 12

18 31 50 10 53 37 12 52 36 55 33 12 27 42 31 18 47 35 19 46 34 23 65 12 44 46 10 55 39 7 64 30 6 55 39 6 86 10 4 84 15

19 35 46 16 45 39 17 48 35 60 30 10 28 45 28 18 61 21 21 49 30 23 66 11 44 45 11 64 30 6 71 24 5 63 31 6 86 9 6 86 11

21 35 44 16 50 34 15 52 33 61 29 10 30 41 29 21 52 27 22 50 29 22 68 10 48 43 8 66 29 5 72 24 4 62 33 5 88 7 5 88 10

18 31 51 12 47 41 15 47 38 60 29 12 29 39 32 17 56 27 22 50 28 28 62 10 41 48 11 51 40 9 63 29 8 56 35 9 84 10 6 80 17

16 33 51 11 49 40 13 50 37 50 38 12 23 50 28 16 55 29 16 44 40 19 66 14 40 47 13 58 37 5 65 30 5 57 38 5 84 12 3 85 13

18 35 47 12 52 35 14 52 33 56 34 10 25 46 29 16 55 29 19 49 32 23 65 12 43 46 11 59 35 6 66 27 6 59 35 6 87 9 4 85 14

14 37 49 18 39 43 20 48 32 56 35 9 32 45 23 19 63 18 19 49 32 15 72 14 38 53 9 59 34 7 68 26 5 55 39 6 85 11 4 79 17

21 23 56 9 51 40 10 46 45 55 24 21 27 39 35 21 50 30 15 50 36 22 66 12 43 45 13 58 33 9 69 24 7 62 29 9 78 12 10 86 9

29 21 50 17 46 38 17 54 29 71 21 8 38 33 29 29 50 21 29 50 21 21 75 4 54 42 4 63 33 4 67 33 0 63 38 0 100 0 0 100 0

22 34 45 17 45 39 19 46 35 63 25 12 36 40 24 23 47 30 30 37 33 31 65 4 51 42 7 59 37 4 69 28 4 60 36 4 84 13 2 57 11

18 36 45 12 39 48 3 45 52 58 36 6 21 27 52 9 55 36 21 45 33 24 55 21 55 36 9 73 24 3 67 30 3 58 39 3 94 3 3 94 3


Q28

Q29

Q30

Q31

Q32

B F N B F N B F N B F N B F N B

2 76 21 3 60 35 5 72 24 4 84 13 3 86 11 3

2 81 18 2 65 32 3 70 27 3 88 11 2 89 9 2

3 82 12 6 74 22 3 81 17 2 86 10 4 89 9 2

1 77 21 2 67 30 3 66 32 3 85 14 2 87 10 2

2 78 20 2 60 37 4 74 22 5 87 11 2 87 10 3

3 73 24 4 49 44 7 71 26 3 84 13 3 84 13 2

1 76 22 2 60 36 4 72 26 3 87 11 2 87 11 2

3 79 18 4 64 32 4 72 24 4 84 13 3 87 11 3

2 82 16 2 63 35 2 78 19 2 86 11 2 89 9 2

3 73 23 4 61 32 7 70 26 3 85 12 3 85 11 3

2 75 22 3 61 35 4 64 31 5 85 13 2 85 12 3

1 77 21 2 62 34 5 69 28 3 85 13 2 86 12 2

4 74 23 3 57 39 4 75 22 3 88 11 1 86 12 2

5 74 20 6 64 32 4 69 24 7 84 12 4 85 11 4

0 96 4 0 63 33 4 79 21 0 88 13 0 100 0 0

2 80 18 2 61 35 4 82 16 2 87 10 4 87 11 2

Supplementary Table 1. For each factor and each subgroup, the percentage of responses that rated that factor as a facilitator, neutral, or a barrier. Rows (Factors): Q1 Being a “guinea pig” Q2 Not knowing if your condition will improve Q3 Possible improvement in your functionality Q4 Possible decline in your functionality Q5 Possible side effects Q6 Wish to be more independent Q7 Possibility of being in the “control group” (not receiving the active intervention) Q8 Religious issues Q9 Privacy issues Q10 Possible out-of-pocket expenses Q11 Time commitment Q12 Concern about losing medical coverage/access to medical care Q13 Concern about losing your income Q14 Transportation to/from the research facility Q15 Work obligations Q16 Family obligations Q17 Family support and encouragement Q18 Possible impact on family or friends Q19 Possible impact on caregiver/attendant/assistant

3 85 12 3 67 33 0 76 15 9 82 12 6 97 0 3


Q20 Require help to perform what is required in the trial Q21 Experience with previous clinical trials Q22 Knowledge about clinical trials Q23 Recommendation from your doctor Q24 Recommendation from other people with SCI Q25 Recommendation from SCI consumer organizations Q26 Opportunity to help future people with SCI even if you do not experience improvement Q27 Opportunity to learn more about your general health Q28 Opportunity to receive free (extra) medical tests or treatments Q29 Possibility to earn a small amount of extra money, if offered Q30 Need to retain a positive attitude “Never give up hope!” Q31 Access to cutting edge care Q32 Better understanding of your SCI Columns (Subgroups): Gender – male Gender – female Current age group – 18-30 Current age group – 31-45 Current age group – 46-60 Current age group – >60 Injury level – tetraplegia Injury level – paraplegia Injury duration group – 0-10 years Injury duration group – 11-20 years Injury duration group – >20 years Region of residence – USA Region of residence – Europe Region of residence – Canada Region of residence – Asia Region of residence – Oceania Region of residence – Latin America and Caribbean Abbreviations: F – Facilitator; the number equals the percentage of responses that were +1, +2, and +3 N – Neutral; the number equals the percentage of responses that were 0 B – Barrier; the number equals the percentage of responses that were -1, -2, and -3