Trends in collaboration with patient organizations on cancer-related clinical trials: Collaborative relationship with existing stakeholders and the characteristics of their co-sponsored studies in the United States

doi:10.21203/rs.3.rs-2011819/v1

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Research Article

Trends in collaboration with patient organizations on cancer-related clinical trials: Collaborative relationship with existing stakeholders and the characteristics of their co-sponsored studies in the United States

https://doi.org/10.21203/rs.3.rs-2011819/v1

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Background

In recent years, the importance of patient centricity in drug development has been recognized, affecting the stakeholders conducting clinical trials. In this context, end users, patients and patient organizations are becoming increasingly involved in the development process to address their unmet medical needs. However, there is a lack of research on environmental trends in which patient organizations collaborate with incumbent stakeholders in drug development. This study aimed to understand the current status of clinical trials regarding patient organization involvement as sponsors and collaboration with different types of sponsors in cancer-related clinical trials. This cross-sectional study also examined the characteristics of clinical trials involving patient organizations as new stakeholders by analyzing the environmental factors that promote collaboration with existing stakeholders.

Methods

A total of 14,830 interventional clinical trials registered on ClinicalTrials.gov between January 1, 2010, and December 31, 2020, were categorized and analyzed by target cancer types and five different sponsor types: 1. patient organization co-sponsored (PO-co), 2. academia (ACD), 3. governmental (GOV), and 4. industry co-sponsored (IND-co) and 5. industry only (IND).

Results

PO-Co studies accounted for 2% (289 of 14,830) of the total studies, ACD 5%, IND-Co 21%, GOV and IND 36%. When the 289 PO-Co studies were analyzed by cancer type and eligible study population, we found that the proportion of pediatric studies was significantly higher for PO-Co studies (30% (88 of 289)) than for total studies (9% (1,378 of 14,830); P < .001), and we also found that collaboration with PO was more common for certain cancer types compared with the total study. Regarding collaboration with POs, more than half of the PO-GOV collaborative studies were conducted at the Nation cancer center comprehensive cancer centers, and even particular investigators actively engaged in collaboration with POs.

Conclusions

A cross-sectional analysis of cancer-related clinical trials revealed that the involvement of patient organizations as sponsors in clinical trials did not increase significantly over time. However, some organizations have become actively engaged in certain cancers and pediatric populations that are less prioritized by incumbent sponsors. We also found that governmental sponsors and selected principal investigators played an important role in collaborating with patient organizations. These findings provide a basis for understanding the current status of patient organizations and for considering further contributions.

patient organization

patient centricity

clinical trial

cancer

pediatrics

public policy

organization management

Reflecting on the patients' opinions in the process is crucial to properly understand what patients want. This study aimed to understand the current status of clinical trials in terms of patient organization involvement as sponsors, and collaboration with different types of sponsors. An analysis of cancer clinical trials conducted in the United States over 11 years beginning from 2010, showed that patient organizations are actively engaged in certain cancers and pediatric populations are less of a focus for industry sponsors. Regarding collaboration with POs, more than half of the collaborations between patient organizations and governmental sponsors were conducted at certain comprehensive cancer centers, and certain investigators also tended to be actively engaged in collaboration with patient organizations. We believe that governmental sponsors and principal investigators play an important role in collaborating with patient organizations.

In recent years, the importance of patients in the drug development process has been recognized [1–3], by key stakeholders conducting clinical trials [4–6]. Therefore, patients as end users of drugs are increasingly involved in the development process to respond to their own unmet medical needs, in addition to drug developing companies such as pharmaceutical and biotechnology companies or medical institutions providing medical services [7–10]. However, because the direct participation by individual patients is limited, patient organizations or advocates representing patients and their diseases have been cited as important collaborative stakeholders for an effective collaborative process [6, 11, 12]. Although some have questioned the representativeness of these organizations as not adequately reflecting patient populations due to low patient participation [13–15] and financial conflicts of interest with industry entities [16–18], the role of patient organizations has expanded to deliver patients' opinions, including basic research and health technology assessment, leveraging the perspectives and expertise of patients experiencing the disease [19–23].

The industry has been working on various approaches to integrate patient voices into the process through collaboration with patient organizations at each stage of clinical development [24–28]. This new approach, patient and public involvement, and patient engagement have contributed to conducting more patient-centric clinical trials by optimizing study participation criteria [29] and patient-relevant priorities and outcomes [30]. However, there are few studies on environmental trends in which patient organizations collaborate with traditional stakeholders in drug development.

This study aims to investigate the current status of clinical trials in terms of the involvement of patient organizations as sponsors, the most active form of engagement in the process, and their collaboration with different types of sponsors. This cross-sectional study examined the characteristics of clinical trials involving patient organizations as new stakeholders by analyzing the environmental factors that promote collaboration with existing stakeholders. Because each disease has different medical needs and patient organization involvement may have different characteristics, we focused on trials related to cancer, the most active area of drug development [37]. To control for other country-specific factors in which a clinical trial is conducted, the analysis was limited to trials conducted in the United States, where most clinical trials are also conducted worldwide [37]. In this study, we analyzed the characteristics of human clinical trials involving patient organizations as sponsors or collaborators and trends in collaboration with other organizations.

This study used ClinicalTrials.gov (hereafter referred to as CT.gov) as the primary database. CT.gov is the largest clinical trial registry in the world and has been analyzed in many studies to understand the current status and trends of ongoing and completed clinical trials [31–34]. In particular, the data on "Sponsor/Collaborator", which plays a central role in the conduct of clinical trials, is important because sponsors in clinical trials are not only the funders but also the organizations responsible for planning, conducting, and reporting the trials [31, 32]. It will help us to understand the clinical trial environment, the nature of the sponsor, and the collaborative relationship in the development of new treatments and drugs [35, 36].

Dataset

The clinical trials dataset was created from CT.gov using the following conditions: condition or disease (cancer), study type (interventional), study results (all studies), status (all), country (United States), phase (all), funder (all), and study start date (from January 1, 2010, to December 31, 2020) (search date: December 04, 2021). A total of 14,830 records representing all interventional clinical trials registered on CT.gov for cancer-related diseases in the United States from 2010 to 2020 were identified (refer to Additional file 1: The dataset of cancer-related clinical trials conducted in the United States from 2010 to 2010 from CT.gov). The "Sponsor/Collaborator" from the dataset was our primary focus in understanding the relationship between the patient organization and the dataset, but the "Conditions" also gave us important insights into how different types of sponsors participate in drug development [38]. Therefore, both "Sponsor/Collaborator" and "Conditions" were classified based on the sponsor and cancer type categories in Additional File 5. In this study, we did not precisely define the difference between "Sponsor and Collaborator" but considered them as equivalent sponsors because the dataset did not contain information on the detailed roles of each organization [32]. Existing studies using CT.gov often classify sponsors into the industry (pharmaceutical and industry-related companies) and non-industry (non-corporate) groups [31, 33, 34], but in this study, sponsors were categorized into five different groups to understand their unique characteristics and further analyze the factors that lead "patient organizations" to participate as sponsors/collaborators in clinical trials, as well as their collaborations with other organizations.

Sponsorship categories and classification criteria

Specifically, for organizations that fall under the non-industry category, we identified patient organizations, academic organizations (universities, medical institutions, research networks, etc.), and governmental agencies such as the National Cancer Institute and its designated cancer centers [39], which are leaders in cancer research in the United States [40–42], as separate categories. Below are the five sponsorship categories for each study in the dataset: 1. PO-Co, 2. ACD, 3. GOV, and 4. IND-Co, and 5. IND. In addition to these categories, co-sponsorship with GOV was highlighted separately as GOV total, as it was often included in other categories such as PO-Co and IND-Co. We compared changes during the analysis period by sponsor and cancer type.

We defined patient organizations as "nonprofit organizations that support patients and families and work to improve the medical environment for patients and families with the relevant cancer type" based on the European Medicines Agency definition, as there is no internationally agreed definition of "patient organization" [43]. However, some charities that donated in areas other than supporting cancer patients and their families were excluded from the analysis. And nonprofit organizations formed to research specific cancers and diseases (consortia, research networks, etc.) were classified as academic organizations. Patient organizations were identified as references based on their mission, vision, and activities (e.g., patient support activities) on their official websites and nonprofit organization information websites. (Additional file1)

Because the number of patients and their medical needs differ by cancer type, we classified the dataset by cancer type (Additional file 5) to investigate how patient organizations actively engage with each cancer type. Cancer types were independently created based on the WHO classification of tumors [44]. Some diseases related to a specific cancer type were also included in the cancer criteria, but diseases that did not fall under any cancer category were excluded from the analysis for cancer type.

Results of analysis by sponsor categories

A total of 14,830 interventional clinical trials registered between January 1, 2010, and December 31, 2020, were categorized by sponsor type according to the categories in the Additional files. Figure 1 shows an overview of studies conducted by sponsorship. PO-Co studies accounted for 2% of total studies, ACD 5%, IND-Co 21%, GOV, and IND 36%. We also classified studies co-sponsored by organizations that fall under the GOV category as an additional analysis group (GOV total). This indicated that governmental organizations were involved in 53% (7,931 of 14,830 registered trials) of the total studies. Regarding changes in the number of clinical trials conducted by each sponsor over time, there was an overall trend toward an increase in the number of trials conducted and a slight increase in the percentage of industry-related studies (IND and IND-Co). There was also no trend in the percentages of PO and ACD. The averages for the study period (2010–2020) were 2% and 5%, respectively.

Status of patient organization-sponsored studies

The 289 PO-Co studies were classified and analyzed for each cancer type to better understand their characteristics. We found that the proportion of pediatric studies was significantly higher (P < .001) in PO-Co studies (30%; 88 of 289) than in total studies (9%; 1,378 of 14,830). Figure 2 shows the details of the overall study and the PO-Co study in terms of the number of studies and the proportion of studies in which the pediatric population was eligible to participate. Among individual cancers, 82% (37 of 45) of brain-related, 71% (17 of 24) of unclassified, and 58% (11 of 19) were open to pediatric patients, representing 33% (306 of 937), 11% (277 of 2590), and 16% (150 of 965), respectively, in the overall study.

We also found that collaboration with PO was more pronounced in certain cancer types compared with the overall study (see Fig. 2). Hematology-related studies (Hema) were the most common cancer type (25%; 73 of 289) in the PO-Co studies, as they were in the overall studies (24%; 3,514 of 14,830). Brain and breast cancers were the next most common cancers, accounting for 16% (47 of 289) and 16% (46 of 289), respectively) of PO-Co studies, with higher rates of collaboration compared with the overall study (6% (937 of 14,830) and 8% (1157 of 14,830), respectively). On the other hand, lung cancer (3% (9 of 289)) and unclassified cancer (8% (23 of 289)) had lower PO-Co rates compared with the overall study (8% (1,115 of 14,830) and 17% (2,590 of 14,830), respectively).

Relationship with Early Termination of Trials

Clinical trials can be suspended, withdrawn, or even terminated for various reasons before or during the trial (hereafter referred to as "early termination"). It is also a major problem that there are many obstacles to recruiting the targeted number of subjects within the trial period [45, 46]. We analyzed the reasons for early trial termination in five cancer types (brain, breast, gastrointestinal, genitourinary/gynecologic, and hematopoietic/lymphoid tissue) to compare the rate of early termination and the reasons for trials sponsored by each sponsor category (see Additional file6). Table 1 summarizes the background reasons for premature termination by sponsor and cancer type (at the time the database was acquired from CT.gov). The reasons for early termination were classified into the following five categories: 1. subject recruitment (accrual) and feasibility of conducting the study; 2. efficacy and/or safety of the investigational drug; 3. changes in the development plan or strategy of the company developing the drug; 4. funds, logistic-related; and 5. principal investigator in charge of conducting the trial. There were also some studies where no detailed information was disclosed or that were restarted when they were confirmed as of April 2022.

Among the five cancer types analyzed, there was no clear trend in termination rate and its background, whereas there was a significant difference between sponsor categories (P < .001); 30% of ACD-led studies were prematurely terminated, compared with 19–20% for other sponsors. It became clear that subject recruitment was the main reason for premature termination, as accrual/feasibility accounted for 41–49% of ACD, GOV, and IND-Co. However, the impact of subject recruitment on early termination was relatively small at 35% for PO-Co and 19% for IND. When the primary sponsor was ACD or GOV, the number of early terminations due to the primary investigator tended to increase.

Table 1

Background of early termination by sponsor and cancer type
Reasons for early termination	Total number of studies	Number of studies by cancer type (%)					Number of studies by the sponsor (%)
Reasons for early termination	Total number of studies	Brain	Breast	Gastrointestinal	Genitourinary/ Gynecologic	Hematopoietic / lymphoid tissue	Patient organization co-sponsored	Academy	Governmental	Industry co-sponsored	Industry
Accrual/ Feasibility	664	66 (37.7)	76 (37.4)	122 (34.5)	153 (38.3)	247 (33.2)	15 (34.9)	79 (49.1)	287 (40.5)	187 (42)	96 (18.5)
Efficacy/Safety	298	22 (12.6)	31 (15.3)	65 (18.4)	60 (15.0)	120 (16.2)	8 (18.6)	15 (9.3)	79 (11.2)	72 (16.2)	124 (23.9)
Sponsor/Development Plan	307	25 (14.3)	37 (18.2)	49 (13.8)	54 (13.5)	142 (19.1)	4 (9.3)	12 (7.5)	50 (7.1)	53 (11.9)	188 (36.3)
Funding/ Resource	189	23 (13.1)	20 (9.9)	39 (11)	40 (10)	67 (9)	9 (20.9)	21 (13)	97 (13.7)	61 (13.7)	1 (0.2)
Others*	417	39 (22.3)	39 (19.2)	79 (22.3)	93 (23.3)	167 (22.5)	7 (16.3)	34 (21.1)	195 (27.5)	72 (16.2)	109 (21)
Total Early termination	1875	175 (100)	203 (100)	354 (100)	400 (100)	743 (100)	43 (100)	161 (100)	708 (100)	445 (100)	518 (100)
Note; p-value = by the sponsor; P < .001, by cancer type; P > .05, see Additional file7

Others༊: studies including no information available and became active as of Apr.2022

Results of Analysis of a collaborative relationship with Patient Organizations

A total of 289 studies (2% of total studies) were sponsored/co-sponsored by 85 organizations classified in this study as PO, and most studies were conducted in collaboration with organizations in other categories, except for one study conducted only by PO. (Fig. 3). Forty-three POs participated in only one study, and 16 POs had more than five studies between 2010 and 2020. Most POs were found to be from patient-related parties (74 of 85), including 34% for pediatric patients (29 of 85). In terms of cancer type, the number of POs related to brain tumors was the highest (19 of 85). 79% (278 of 289) of studies were co-sponsored by GOV organizations, which was even higher than that for studies overall (53%, 7,931 of 14,830). To analyze the relationship between PO and other sponsors, we focused on studies sponsored by GOV and IND, which had a higher percentage of collaborations.

Collaborative Trends of POs

Sixty-nine IND sponsors were identified that collaborated with POs. To compare the characteristics of IND sponsors by company size, we analyzed them by the total number of studies sponsored by each company during the analysis period. Because collaboration with GOV-IND is more active in PO-Co-studies than in other studies, we also compared the percentage of studies co-sponsored by PO-IND-GOV (PO-IND-GOV collaboration rate) and the percentage of studies co-sponsored by GOV in all studies (IND-GOV total collaboration rate). We found that 48 IND sponsors conducted only one PO-Co study regardless of the total number of sponsored studies and showed no trends in their collaboration rate with GOV. However, as we see in the top 20 companies for the number of studies in Fig. 4, for larger IND companies that sponsored more than 300 studies, there is an increasing trend for IND-GOV-PO collaboration compared to their IND-GOV total collaboration.

The analysis of collaboration between PO-GOV focused on the NCI-affiliated organizations because most PO-GOV collaborative studies included the NCI and/or NCI-designated comprehensive cancer centers (hereafter NCI-CCC), which are 51 leading cancer research centers in the United States (as of December 2022) [40–42]. The top 20 NCI-CCCs that had sponsored/co-sponsored more than 100 clinical trials were selected for further analysis. The numbers and percentages of each NCI-CCC sponsored and industry co-sponsored trial (IND-Co) are summarized in Table 2. The percentage of IND-Co varied widely across sites, ranging from 5–67%. The number of PO-GOV-Co studies did not correlate with the number of total studies, but sites with higher IND-Co rates tended to collaborate more frequently with PO.

Table 2

Clinical trials sponsored by NCI-designated comprehensive cancer centers (Top20 for the number of studies)
Name of NCI comprehensive cancer centers	Number of studies (%)
	Total	NCI-CCC only		IND co-sponsored
	Total		PO-co		PO-co
Dana-Farber/Harvard Cancer Center	367	121 (33)	12	246 (67)	15
H. Lee Moffitt Cancer Center and Research Institute	166	55 (33)	5	111 (67)	3
Winship Cancer Institute at Emory University	127	51 (40)	4	76 (60)	0
Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco	182	75 (41)	6	107 (59)	14
Duke Cancer Institute at Duke University	138	63 (46)	3	75 (54)	2
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine	250	128 (51)	10	122 (49)	12
Memorial Sloan-Kettering Cancer Center	460	236 (51)	2	224 (49)	2
UPMC Hillman Cancer Center at the University of Pittsburgh	115	60 (52)	1	55 (49)	0
Roswell Park Comprehensive Cancer Center	110	63 (57)	0	47 (43)	0
The Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at Ohio State University	110	54 (49)	1	45 (41)	1
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine	205	132 (64)	5	73 (36)	3
Fred Hutchinson Cancer Research Center	105	75 (71)	1	30 (29)	2
The University of Texas MD. Anderson Cancer Center	838	605 (72)	8	233 (28)	3
Stanford Cancer Institute at Stanford University	160	117 (73)	2	43 (27)	1
University of Chicago Comprehensive Cancer Center	107	81 (76)	2	26 (24)	1
University of Michigan Rogel Cancer Center	120	97 (81)	4	23 (19)	0
Abramson Cancer Center at the University of Pennsylvania	179	156 (87)	3	23 (13)	1
Mayo Clinic Cancer Center	247	219 (89)	3	28 (11)	1
Case Comprehensive Cancer Center	106	100 (94)	0	6 (6)	0
City of Hope National Medical Center	153	145 (95)	0	8 (5)	0
Note: CCC: comprehensive cancer centers. The top 20 CCC sites were listed by the number of trials in order of IND-Co%. The trials conducted by multiple NCI-CCC sites in collaboration were counted in duplicate because the studies in which each NCI-CCC participated as a sponsor were totaled.

Table 3 summarizes the number of studies conducted by NCI-CCC and particular principal investigators for five cancers that were found to have a higher number of PO collaborations. More than half of the PO-GOV collaborative studies were conducted at specific NCI-CCC sites, and even particular investigators tended to be actively engaged in PO collaborations. For example, at the University of California, San Francisco, where 32 brain studies were conducted, we found that 7 studies collaborated with POs, of which one investigator was responsible for the 6 studies, while 20 investigators conducted clinical trials at the site.

Table 3

The number of NCI-comprehensive cancer centers and principal investigators involved in studies of five cancer types
Cancer type/ NCI-CCC and PI	Number of GOV-PO-Co- studies	NCI- comprehensive cancer centers		Principal Investigator
Cancer type/ NCI-CCC and PI	Number of GOV-PO-Co- studies	Number of Sites with multiple PO-Co-studies	Number of studies (% to total)	Number of PIs with multiple PO-Co-studies/ Total PIs	Number of studies (% to total)
Brain	35	5 sites	17 (49)	3/30	10 (29)
Breast	42	9 sites	26 (62)	6/35	13 (31)
Gastrointestinal	29	5 sites	18 (62)	4/26	8 (28)
Genitourinary/Gynecologic	28	6 sites	20 (71)	5/23	10 (36)
Hematopoietic/lymphoid tissue	50	8 sites	31 (62)	5/37	18 (36)

Characteristics of PO co-sponsored studies

This study has shown that PO-Co trials have been used to identify trends in PO participation in drug development. It was anticipated that PO participation would actively increase because of the recognition of the importance of considering patient opinion in the development process. Although the total number of clinical trials has increased over the past 11 years till 2020, the percentage in each sponsor category has not changed significantly, especially for PO-Co trials that were conducted in only 2% of the total trials each year.

However, when each sponsor's studies were crossed by cancer type, different trends were observed for the overall study and the PO-Co study. In particular, brain and breast cancer studies had high PO-Co rates, and these cancers were characterized by GOV sponsors conducting more studies than INDs. For many cancers, GOVs conduct a greater number of trials than INDs or at the same level as INDs. However, in the lung cancer study, where INDs conducted more trials than GOVs, the rate of PO-Co was low. Given the differences in PO-Co rates between these cancers, GOVs were considered to be actively participating in areas where treatment is relatively underdeveloped, i.e., where there is an unmet medical need.

Additionally, the proportion of pediatric studies in the PO-Co study tended to increase. Especially in the brain area, it was not surprising that 82% of the PO-Co studies were eligible for pediatric patients, as many brain-related POs were founded by families of pediatric patients. It was also confirmed that 34% of POs (29 of 85) focused on supporting pediatric patients (Additional File 2). Considering the current situation in which drug development for the pediatric population has not progressed regardless of the type of cancer [47–49], this finding suggests that there is a gap between the unmet medical needs of patients and the development strategies of IND companies. At IND sponsors, where the development of innovative drugs that meet the patient’s needs are directly linked to growth, it is conceivable that patient-centered drug development that involves patients in the process will continue to be important.

Measures for early termination of clinical studies

When analyzing trends in premature termination for different sponsors and five cancer types, there were no significant differences among cancer types. However, the analysis of sponsors provides important insights, particularly concerning patient recruitment. As confirmed in previous studies, "Accrual/Feasibility" is the most crucial issue for most sponsors when conducting clinical trials [45, 46]. For ACDs, GOV, and IND-Co, the proportion was 41–49%, but for POs and INDs, it was 34.5% and 18.5%, respectively. In the case of INDs, a unique feature of INDs is thought to have contributed to a lower termination rate due to accrual: 93% of trials led by IND were conducted at multiple centers (IND-Co: 46%, NCI: 37%, ACD: 26%, and PO: 52%; see Additional file 1).

It was not surprising that IND sponsors with the lowest budget-related early termination were likely to conduct a larger multi-center study. This could improve patient recruitment and achieve a larger sample size to increase statistical power [50, 51]. However, this also brings scientific and operational challenges, such as standardizing a process across sites [52–54]. Therefore, this may not be the best solution for every sponsor. On the other hand, it is interesting to see that PO-Co studies have a lower early termination rate than other sponsors, while PO-Co studies are mostly collaboratively conducted with others. Although we could not define the role and responsibilities of PO for each study because of the limited information in the database, this provides a clue to solving the problem of patient recruitment in a clinical trial. Further research is required to systematically analyze the role and contribution of each PO in PO-Co studies to understand how this might be applied to future collaboration and active PO involvement in drug development.

Collaboration model around POs

In terms of the relationship with other sponsors in PO-Co studies, there were no significant differences between IND sponsors based on the number of studies conducted, which represent the size of the company. However, as size increases, IND-GOV-PO collaboration rates tend to increase, suggesting that GOVs play a central role in larger IND sponsors in terms of PO collaboration. In terms of the GOV-PO relationship, the results of the analysis of NCI-CCC sites also highlight a similar trend: NCI-CCCs with a high GOV-IND collaboration rate tend to participate more in PO-Co studies. In other words, NCI-CCC sites that conduct many trials in collaboration with other sponsors may be better suited for PO collaboration than other sites that perform them within GOVs.

Moreover, certain PIs were more engaged in PO collaborations for all five cancer types analyzed. These PIs tend to be members of specific consortia or national research institutes, in addition to the NCI-CCC to which they belong. There are also cases of collaboration with a specific group or multiple groups. To understand the characteristics of PIs participating in multiple PO-Co studies, one must also consider their relationship with other collaborative sponsors and the objectives of the trials. However, it has been suggested that PIs play an important role in ongoing collaboration with POs.

Various IND sponsors strive to adopt a patient-centric approach to drug development, particularly in the conduct of clinical trials, to achieve important outcomes for patients as end users of their product, but have difficulty establishing the process [6–8, 12]. The results of this study suggest that governmental cancer research institutes and medical institutions that provide innovative treatments, such as NCI-CCC, play a leading role in collaborating with POs, as shown in Fig. 5.

Limitations and future perspectives

This study focused on organizational structure and collaborative relationships to understand how POs engage with other types of sponsors in the context of a clinical trial. However, because the analysis was limited to information published in the CT.gov database, each sponsor/collaborator was consequently treated as an equivalent sponsoring organization without considering its role and contribution to the study. We decided that it was not necessary to understand the details to capture the overall picture of collaboration between organizations. Furthermore, we did not include an analysis of investigational drugs and/or medical devices with different modalities that might influence the scientific design or development strategy. We conclude that it is not essential to track the involvement of POs, which are typically established according to cancer type. Finally, this study was limited to clinical trials related to cancer and may differ in other disease areas.

Data from CT.gov used in this study were analyzed based on information provided by individual sponsors. Sponsors are required to enter accurate information and its progress in a timely manner, but this is not always done as it should be [55–56]. Although some data were missing or incomplete, we were able to verify the correct information on the trial page on CT.gov Therefore, we did not believe that this would have a large impact on the overall analysis. Sponsors and cancer types were classified according to the category criteria in the additional files. Specifically, for POs, we confirmed the mission/vision and activities of each organization to identify nonprofit organizations that support patients and their families in cancer-related areas. However, nonprofit research organizations were categorized as academies (ACD), and nonprofit organizations that also donate in areas other than cancer were not specified as POs. Consistency of data was ensured because the classification was performed by a researcher according to consistent criteria across the dataset, although it was subjectively performed. Each study classified by sponsor and cancer type was aggregated and analyzed according to study interest, such as availability to the pediatric population and reason for early termination under the same conditions.

A variety of stakeholders participate in clinical trials with the common goal of responding to patients' unmet medical needs. Therefore, consideration of patients' views in this process is a critical step to better understanding patient preferences. This cross-sectional analysis of cancer-related clinical trials conducted in the United States from 2010 to 2020 found that patient organization participation in clinical trials as sponsors did not increase significantly over time. However, we found that patient organizations are actively engaged in the particular cancer types and pediatric populations that are less of a focus for IND sponsors. We also believe that GOV sponsors and investigators play an important role in collaborating with patient organizations. We hope that this research will help us understand where we are now and what is next when it comes to engaging patient organizations in clinical trials.

Patient Organization

IND

Industry sponsor

GOV

Governmental sponsor

ACD

Academy

NCI

National Cancer Institute

CCC

Comprehensive Cancer Center

Brain

Brain and nerve system-related cancer or disease

Breast

breast-related cancer or disease

H&N

Head and neck-related cancer or disease

Lung

Lung and thymus-related cancer or disease

Gastrointestinal-related cancer or disease

GE/GY

Genitourinary/Gynecologic-related cancer or disease

Hema

Hematopoietic and lymphoid tissue-related cancer or disease

S/T/B

Skin

tissue

and bone-related cancer or disease

NON

Non-specific or more than 2 cancer type.

Ethics approval and consent to participate: Not applicable

Consent for publication: Not applicable

Availability of data and materials: All data analyzed during this study are included in this published article and its supplementary information files.

Competing interests: The authors declare no competing interests.

Funding: This study was supported by JSPS KAKENHI Grant Number 21H00739.

Author’s contributions: All authors meet the criteria for authorship. All authors were involved in developing and revising the manuscript. All authors read and approved the final manuscript.

Acknowledgments: We would like to thank all the people who contributed in some way to delivering this research, especially the related member of the Tokyo Institute of Technology and Ritsumeikan University.

Authors’ information: 1. Department of Technology and Innovation Management, School of Environment and Society Tokyo Institute of Technology, Tokyo, Japan

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No competing interests reported.

Additionalfile1.ThedatasetofcancerrelatedclinicaltrialsconductedintheUS.xlsx.xlsx
Additional file1. The dataset of cancer-related clinical trials conducted in the United States from 2010 to 2010 from Clinicaltrials.gov.
Additionalfile2.Thelistofpatientorganizationsponsors.xlsx
Additional file2. The list of patient organization sponsors
Additionalfile3.Thelistofindustrysponsorswhichcollaboratedwithpatientorganization.xlsx
Additional file3. The list of industry sponsors, which collaborated with patient organizations
Additionalfile4.ThelistofNCIComprehensiveCancerCenterAsofDec.2021.xlsx
Additional file4. The list of NCI-Comprehensive Cancer Centers (As of Dec.2021)
Additionalfile5.Thelistofkeywordstoclassifycancertype.xlsx
Additional file5. The list of categories and keywords to classify cancer type
Additionalfile6.Thelistofearlyterminationstudies.xlsx
Additional file6. The list of early termination studies
Additionalfile7.ChisquaretestforTable1andFigure2.xlsx
Additional file7. Chi-square test for Table1 and Figure2

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Trends in collaboration with patient organizations on cancer-related clinical trials: Collaborative relationship with existing stakeholders and the characteristics of their co-sponsored studies in the United States

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