Collaborative relationships in translational medical research among Chinese clinicians: an internet-based cross-sectional survey

Background This study aimed to explore the collaborative relationship in translational medical research from the perspective of clinicians in China. The findings are expected to help practitioners optimize and experience the greatest advantages of collaboration. Methods We conducted a national internet-based survey from July 29 to October 12, 2020. Of the 806 responses, 804 were completed with valid responses (valid response rate = 99.8%). The collected data were presented as descriptive statistics and analyzed using nonparametric tests (including the Wilcoxon rank test and Kruskal–Wallis H test) and stepwise logistic regression. Results Of the 804 participants, 733 were either willing or very willing to collaborate in translational medical research. Clinicians’ willingness was influenced by their current research type, role in current translational medical research, burdens of their present research, preferred partners for collaboration at the institutional or individual level, and preferences for independent or dependent relationships. Conclusions Clinicians should evaluate their time, role, burdens, personal preferences for research relationships, and appropriate partners based on their current translational medical research and its goals, before deciding to collaborate.


Background
Translational medical research (TMR), which aims to bridge laboratory and clinical research [1], has experienced rapid development in the past 20 years [2]. In TMR, collaboration has become mainstream and is now a fundamental requirement. TMR consists of a continuous process that begins with clinical discovery and medical research and leads to clinical application in patients [3]; it accommodates multiple disciplines and scientists in various fields. However, owing to the professional gap between laboratory scientists and clinicians and the differences among hospitals, universities, research centers, and industries [4][5][6], practitioners need to collaborate at an individual or institutional level to realize the goals of TMR.
Researchers have considered in depth the advantages and disadvantages of collaboration in TMR.
Collaboration, especially in a multidisciplinary team, is widely recognized to be of great significance and necessity in TMR [7]. Although "translation" has different meanings for different stakeholders, the overall aim is to benefit humankind by promoting the application of clinical findings and laboratory achievements. Therefore, collaboration among clinicians, laboratory scientists, industrial scientists, biotechnologists, and politicians in different institutions can bring these stakeholders together, help them understand one another professionally, and motivate TMR [8,9]. Among all the merits of collaboration in TMR, the most prominent is knowledge exchange, which can help elucidate scientific questions, promote laboratory research, and accelerate clinical application [3,[10][11][12][13][14]. A bibliometric research further confirmed the role of collaboration in TMR, especially in terms of knowledge exchange [15]. Therefore, based on such knowledge exchange and mutual understanding, collaboration between researchers and clinicians is crucial for the translation and application of laboratory biomedical discoveries to patients and to clinical practice [16][17][18][19]. Additionally, collaboration between researchers and industrial scientists can promote the development of medicine [20].
Collaboration in TMR also has its disadvantages and risks. For instance, collaboration in TMR among various partners could lead to greater time expenditure or delay of research plans, owing to diverse academic perspectives or scholarly disagreements [3,21]. Collaboration also tends to cost more, including the time spent in negotiation and exchange, as well as the costs of communication and travel, contradictions in research design and results, and conflicts arising from result sharing [3,14]. Some stakeholders also refuse to collaborate in TMR because of the risks of losing decision-making autonomy and frustration with partners [3].
Considering the characteristics of collaboration in TMR, different practices have been observed, including collaborations at the institutional and at individual levels [7]. In China, current collaborations in TMR mainly focus on the institutional level, such as the Sino-Cuban Joint Working Group on Biotechnology Cooperation [22], and the collaboration between Peking University Health Science Center and the University of Michigan Medical School [23]. However, from the perspective of individuals, their attitudes, viewpoints, willingness, and practice behaviors are important for collaboration in TMR; this is especially true for clinicians, who are situated at the juncture of laboratory and clinical research. This study therefore explored collaborative relationships in TMR from the perspective of clinicians to determine their willingness to collaborate, recognize preferred partners, and determine the factors influencing collaboration.
The results of this study provide key evidence for optimizing collaboration and realizing the greatest advantages of collaboration in TMR.

Study design
We designed an internet-based survey to explore the collaborative relationships in TMR among clinicians in China. The required sample size was determined to be at least 129, which was calculated with a confidence level of 95%, an admissible error of 0.1, and the probability of approval of TMR among clinicians of 74.9% [2]. A preliminary investigation involving 85 clinicians was conducted before the formal survey. Based on the preliminary participants' responses, several items were revised to improve the reliability and validity of this questionnaire. The internal consistency of the formal questionnaire was examined using a Cronbach's α coefficient, which was calculated as 0.930, indicating good reliability. Factorability was tested using the Kaiser-Meyer-Olkin test and Bartlett's test of sphericity, which yielded values of 0.724 and 5103.91 (p < 0.0001), respectively, suggesting good validity.
The formal questionnaire included 24 items that were compiled through a review of references and consultations with experts. Information on demographic characteristics, current status of personal TMR, collaborative willingness in TMR, and perceptions of collaboration in TMR was collected. Items that collected participants' perceptions were rated using a five-point Likert scale.
Regarding demographic characteristics, we analyzed the clinicians' sex, age, educational level, professional title, and department. Regarding the current status of personal TMR, we asked about the clinicians' research type (e.g., clinical, laboratory, or public health management), role in TMR (e.g., principal investigator [PI] or participant), research pressure (low or high), and communication methods used in collaborations (e.g., faceto-face, telephone, or WeChat). The scale of collaborative willingness in TMR contained five items, including willingness to collaborate and preferred collaboration partners at an institutional or individual level. Perceptions of collaboration in TMR were addressed via 11 items that focused on collaborative relationships, positive and negative aspects of collaboration, and factors that influence collaboration. The measure of collaborative relationships explored the preferences for independent or interdependent relationships [24].
Referring to the positive aspects of collaboration, items addressed understanding of collaboration advantages, extra resources made available through collaboration, and improved personal capabilities. The advantages of collaboration included additional funds or resources, knowledge transfer, enhancement of reputation, increase in number of publications, improvement in publication quality, enrichment of academic influence, additional clinical resources, more equipment resources, new technologies, promotion of treatment capability, and acceleration of the research process [3,9,25]. Extra resources made available through collaboration referred to funds, patients, technologies, equipment, talents, and information. Personal capabilities could be improved in terms of communication, receiving new knowledge and technology, and control over research programs.
When considering the negative aspects, we focused on the disadvantages such as the costs, risks, and challenges of collaboration. Disadvantages included more time spent on communication, personal resource transfer to partners, loss of research autonomy and control, deviation from one's main research, and conflicts regarding key research points [3,26]. Collaboration costs included the costs of selecting partners and collecting information, negotiation, implementation, and supervision [9]. The risks of collaboration were identified as the risks associated with coordinating all partners, an imbalance of duties and responsibilities among partners, and dropping out or breaking of promises by partners [27]. The challenges faced during collaboration referred to competition from other research organizations, the ethics review process, insufficient research funds, and the recruitment of project managers [28].
Factors that influence collaboration included those related to the implementation and the success of the collaboration. The former involved factors such as geographical locations, funds, technologies, information, academic status, mutual relationships, and partners' cooperation patterns [29]. The latter included explicit collaboration aims, specific collaboration periods, appropriate partners, clear collaboration rules, clear-cut benefit distribution rules, explicit risk-taking rules, maintaining cooperative network relationships, establishing coordination and supervision mechanisms, specific penalty rules for violations of the collaboration agreement, and definite rules for dealing with disputes or emergencies [30,31].

Data collection
The formal internet-based investigation was conducted from July 29 to October 12, 2020. Of the 806 questionnaires distributed at random to clinicians nationally, 804 were returned with valid responses (valid response rate = 99.8%). The inclusion criteria were (1) clinicians should have TMR experience, (2) all clinicians should voluntarily participate, (3) participating clinicians should complete the survey online and provide informed consent. Those who were not clinicians, did not have TMR experience, or could not complete the online survey were excluded from this investigation. Only completed questionnaires could be submitted to the online survey system.

Statistical analyses
Our statistical analyses were performed using SAS 8.2 (SAS Institute Inc., Cary, NC, USA) and PASW Statistics for Windows, Version 18.0 (SPSS Inc., Chicago, IL, USA). The descriptive statistics, univariate analysis, and multivariate analysis were implemented step by step. First, we employed frequency and percentage to obtain detailed descriptions in the descriptive statistics. Second, the univariate analysis was conducted to confirm the influence of one factor on collaborative willingness in TMR. If p < 0.05, the influence was statistically significant. Third, by including all factors with statistical significance in the univariate analysis, we used a stepwise logistic regression model to determine the influence of multiple factors on collaborative willingness in TMR. In particular, descriptive statistics were used to describe the basic characteristics of the participants. Nonparametric tests, including the Wilcoxon rank test and Kruskal-Wallis H test, were used to test participants' willingness to collaborate in TMR. A stepwise logistic regression analysis was used to analyze the factors influencing the willingness to collaborate in TMR, with inclusion and exclusion criteria of 0.10 and 0.15, respectively. All tests were two-tailed, with p < 0.05 considered to be statistically significant.
Based on the results of the univariate analyses, only factors with a statistically significant influence on collaborative willingness in TMR among clinicians were included in the logistic regression analysis.

Basic characteristics of participating clinicians
Of the 804 participants, 57.5% were men and nearly half were 31-40 years old. Most had a master's degree and an intermediate professional title and worked in non-surgical departments. More than a third (38.1%) of participants were engaged in clinical studies at the time of the survey and most acted as a project participant (not PI). Almost half of participants reported a relatively heavy research burden (based on the five-point Likert scale). The most popular communication method was WeChat (an instant messaging application), with 63.8% reporting using it "often" or "always. " More participants preferred collaborating with individuals rather than with institutions, and the most popular institution type was research institutes. However, their preferences for individuals and institutions varied across different stages of the research. In the research application stage, the most preferred institutions and individuals were research institutes and laboratory scientists, respectively. In the research implementation stage, preferences were for collaboration with research institutes and clinical scientists. In the research achievement promotion stage, preferences were for industrial partners and industrial staff. The number of clinicians who favored independent relationships was nearly equal to those who favor interdependent relationships. Among the advantages of collaboration, improvement in reputation was the most recognized (93.8% agreed or strongly agreed), followed by improved publication quality (93.5%), promotion of knowledge transfer (92.8%), and increased number of publications (92.8%). Information resources were the most recognized extra resources made available by collaboration. The personal capability to receive new knowledge and technology was considered the most positive influence of collaboration.
Of all the disadvantages of collaboration, the transfer of personal resources was considered to be the worst, with 60.1% of the participants agreeing or strongly agreeing. Most participants recognized that the cost, risk, and  challenge of collaboration were the costs of selecting partners and collecting information (89.8%), the risks of unbalanced duties and responsibilities among partners (87.5%), and the challenge of recruiting project managers (87.4%), respectively. The professional technological input of partners was the factor that most influenced desire to collaborate; 92.8% of participants expressed agreement in this respect. For successful collaboration, having explicit collaboration aims (93.4%) and appropriate partners (93.4%) were considered equally important (Tables 1 and 2).

Collaborative willingness in TMR among clinicians Univariate analysis of influential factors
Of the 804 participants, 429 (53.4%) were willing and 304 (37.8%) were very willing to collaborate in TMR, while 14 (1.7%) were unwilling and 57 (7.1%) were uncertain. To explore the relationships between the various factors and clinicians' collaborative willingness in TMR, we performed nonparametric tests. The results (Tables 3 and 4) indicated that 25 factors were statistically significant; these include clinicians' age, education level, professional title, current research type, role in the current TMR, present research pressure, face-to-face communication in collaboration, preferred collaboration partners at the institutional or individual level, and preferences for independent or interdependent relationships. The recognized advantages of collaboration; extra resources brought by collaboration; personal capabilities that might be improved, and perceived disadvantages; costs, risks, and challenges of collaboration; and the factors related to the implementation and success of the collaboration were also factors (all p-values < 0.05).

Logistic regression analysis of willingness to collaborate in TMR
Based on the results of the univariate analyses, only the factors that had a statistically significant influence on   collaborative willingness in TMR among clinicians were included in the logistic regression analysis. The logistic regression analysis results (Table 5) suggested that clinicians' current research type, role in the current TMR, present research pressure, preferred collaboration partners at the institutional or individual level, and preferences for independent or interdependent relationships were statistically significant factors. Greater willingness to collaborate in TMR was associated with clinicians who were not conducting research (compared with those engaged in clinical research, odds ratio [OR] = 0.424), those who were acting as project participants (compared with national PI, OR = 0.396), and those who were more willing to collaborate with individuals or without explicit preferences at the institutional or individual level (compared with those who were more willing to collaborate with institutions; OR = 0.554 and 0.011, respectively). However, less willingness to collaborate in TMR was associated with clinicians with heavier research burdens (compared with those with low burden, OR = 2.591), those preferring to collaborate with hospitals in the research implementation stage (compared with those without such preference, OR = 1.422), and those tending to opt for an interdependent research relationship (compared with those tending to be independent, OR = 1.495).

Discussion
The results of our survey indicated that clinicians' current research situation-including the research type, role, and pressure-preferred partners, and preferences for the research relationship were key factors that influenced their willingness to collaborate in TMR. Moreover, clinician's cognition on translational medicine has an impact on their willingness to collaborate in TMR. Clinicians with more positive attitudes and more knowledge will be more likely to take measures in collaborating in TMR. Those who were not engaged in any research at the time and who were participants in current research programs were more willing to collaborate in TMR, which could be explained by their research pressure or lack thereof. Collaborations in TMR would impose an additional research burden on clinicians, as they would be required to spend more time in communication and resource reallocation [32]. Therefore, clinicians with heavy research loads would be less likely to collaborate in TMR, while those with more time and fewer research responsibilities would be more willing to collaborate. In addition, considering the advantages of TMR collaboration in terms of promoting knowledge transfer and increasing research achievements, clinicians not currently involved in any research or whose involvement was only as a participant would seek more knowledge exchange and increased research achievements through collaboration, which represent incentives for collaboration in TMR [3]. Considering the disadvantages of collaboration, it was shown to weaken control over the research program, which was unacceptable for those undertaking national research projects because such a disadvantage outweighed the merits mentioned above. It is worth noting that some demographic characteristics-such as age, education level, and professional title-would have an indirect effect on clinicians' willingness to collaborate. For example, younger clinicians and those with junior professional titles would be more willing to collaborate due to having more time and fewer research responsibilities as well as for possible knowledge transfer and gaining research achievements. Clinicians with a higher education level would be more willing to collaborate because they may have greater demands for and possibilities of knowledge exchange and research achievements.
Clinicians who preferred individuals as partners, rather than institutions, were more willing to collaborate in TMR. Institutional arrangements are perceived to inhibit collaboration [13], with the compartmentalization of institutions being a main obstruction to collaboration    [7]. Therefore, considering the uncertainty of the potential cooperative institutions, clinicians may be inclined to think that collaborating with individuals would avoid risks such as inappropriate institutional arrangements and structural isolation among different institutions. Moreover, face-to-face communication among clinicians who choose to collaborate with individuals is more likely, which would further promote their willingness to collaborate with individuals. In terms of the benefits of collaborating, working with individuals would also help individual scientists expand the scope and sample size of their research and improve efficiency [9], which is another motivation for collaborating with individuals. Further, considering the preferred institution in the research implementation phase, clinicians who preferred to collaborate with hospitals tended to be more unwilling to collaborate in TMR. A previous study indicated that enhancing the impact of clinical therapy and policy is the core objective of TMR [8]. However, realizing this goal is not easy and it can be time consuming. Such delays may lead to changes, beyond expectations, after collaboration, which consequently impede collaboration in TMR [3]. Thus, although the original aim of collaborating with hospitals was to increase influence by accelerating the clinical application process of research achievements, it would cost more time to realize such translation, which could lead to higher potential risks. The gap between reality and the ideal circumstances would undermine these clinicians' willingness to collaborate. Clinicians who are inclined to be independent in research relationships were more willing to collaborate in TMR. Our results confirmed those of other studies and suggested that the advantages of collaboration would not promote collaboration in TMR [3]. Instead, clinicians who are inclined to be in independent research relationships were less likely to depend on benefits from collaboration, and this tendency facilitated their collaborative willingness. In addition, clinicians who prefer an independent research relationship were more receptive to competing with partners for funds, talent, reputation, and extra support. Such effective and positive competition among partners would promote creativity and excellence [32], which was another form of encouragement for these clinicians to collaborate in TMR.
The results of our study showed that the factors that influenced collaboration in TMR primarily concerned current research characteristics, collaborative partners, and relationships with partners. The advantages and  disadvantages of collaboration were not the main concerns for clinicians when deciding upon collaboration; this indirectly demonstrated that the decision to collaborate was dependent on the feasibility of collaboration (including the availability of time and suitable partners), and that most of the advantages and disadvantages were acceptable, meaning that no additional consideration was required. However, to promote collaboration in TMR, such factors mentioned above should be taken into consideration, which will be helpful to choose more suitable partners and take favorable measures at each stage of collaboration.
The present study has certain limitations. First, most questions in our internet-based survey were selfreported, a method that is prone to potential over-or under-estimation. Second, the study did not distinguish between multi-team systems collaboration and individual collaboration. The factors that influence multi-team systems collaboration and individual collaboration may differ; we will further explore this issue in a follow-up study. Third, we did not consider the role of innovation intermediaries in collaborative TMR. We will explore how innovation intermediaries affect collaborations among clinicians in translational medicine in subsequent studies. Fourth, our survey ignored the leadership role of different agents in TMR. In further surveys, if the preferred partner was an individual (laboratory scientist, clinical scientist, industrial staff, community staff, or health management scientist), the leadership role of clinicians or these individuals should be investigated. If the preferred partner was an institution (university, hospital, research institute, industry, or community) the leadership role of clinicians or these institutions should also be considered.

Conclusions
Most Chinese clinicians who were enrolled in this study are willing to collaborate in TMR. Their willingness to collaborate was mainly based on the current TMR characteristics, potential partners, and inclinations regarding research relationships. To collaborate appropriately and foster the greatest advantages of collaboration in TMR, clinicians should seriously consider the advantages and disadvantages of collaboration. First, clinicians should evaluate their time, role, and research pressure based on their current TMR before deciding to collaborate. Personal preferences for research relationships should also be considered. Second, clinicians should fully consider the goals of their TMR during the entire process and in the different research phases, which would help them choose appropriate partners and address the various costs, risks, and challenges involved in collaborations. Third, several measures could be taken at the national level to accelerate collaboration in TMR, including supporting more resources (e.g., funds), providing training and education programs on the implementation and management of TMR, and giving specific regulations on the responsibilities and rights among partners in TMR.