Therapeutic innovation in oncology: What do you mean? What we cannot talk about, we must keep silent. L. Wittgenstein

Therapeutic innovation in oncology: What do you mean? What we cannot talk about, we must keep silent. L. 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What we cannot talk about, we must keep silent. L. Wittgenstein Sylvie Chevret, Xavier Troussard, Charlotte Masia, Pierre Cochat, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6350857/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Oct, 2025 Read the published version in BMC Cancer → Version 1 posted 9 You are reading this latest preprint version Abstract Background The word “innovation” is widely used in healthcare, especially in oncology. Innovation has been reported to impact the drug evaluation process, but there is no consensus regarding the evaluation of innovation. This study aimed to examine perceptions and attitudes (perceived benefits and concerns) towards innovation in clinical practice and in evaluation of innovation. Patients and Methods : We performed a cross-sectional, online, anonymous, voluntary survey among members of French associations of oncologists, haematologists, pharmacologists and therapists as well as members of the drug evaluation service of the French Health Technology Assessment body. The onlinequestionnaire assessed respondent characteristics as well as their level of agreement with several statements regarding the definition, extent, and evaluation of innovations (Supplementary materials). Most of the items were scored on an 11-point Likert scale. To provide a broader understanding of the respondent profiles, principal component analysis and cluster analysis were performed. Results : A total of 114 participants completed the survey between April and June 2024, including 88 respondents in the oncology group and 26 respondents in the health authoritygroup. There were differences between groups in terms of age, sex, and profession. Three distinctive clusters of respondents were identified: one cluster of respondents looked for simplified evaluation of innovated drugs (all of whom in the oncology group), contrasted to one cluster stated that drug evaluation requires standard processes (almost 80% of whom were in the health authority group); and one cluster of respondents indifferent to the evaluation process (this group has equal distributions across the groups). Conclusion : Innovation is perceived as being associated with the concepts of novelty, advance, and improvement. However, there were differences between groups regarding the level of evidence required to evaluate innovations. Efforts should be done to merge, rather than to oppose, and quantify all different types of evidence, for the patient interest. innovation evidence evaluation Figures Figure 1 Figure 2 Figure 3 Introduction Almost one-half century ago, “innovative” treatments were defined as treatments that “depart in a significant way from standard or accepted practice”. 1 Currently, the terms “innovation” and “innovative” are buzzwords that are widely used in many different fields, including health care. 2 The Collins dictionary defines innovation as the introduction of new ideas, methods, or things. Innovation has then been seen as the initial implementation of a new idea as well as the economic optimization of knowledge utilization. 2 However, there is no comprehensive and generally accepted definition of this term, and different disciplines use various definitions for innovation. This is particularly true in oncology, where any evidence of new mechanisms or technology is considered to be an innovation that should be widely applied by physicians and administered to the public, 3 which stands in contrast with more precautious, evidence-based decision-making in public health agencies. 4 This likely relies on considerable expectations for unmet medical needs, to have something to “offer" to the patient, with increasing difficulty in accepting therapeutic abstention, while ensuring patient safety. 5 Indeed, cancer remains a main burden, with increasing incidence and prevalence, and it is responsible for millions of deaths, thus highlighting the need for more effective treatments for patients. 6 This was recently emphasized by the fact that in 2022, adolescents and young adults accounted for more than 12,000 cancer-related deaths in Europe. 7 In the history of oncology, there is has been a tangled relationship between innovation, “cure,” and death: while palliative measures first summarized the overall fight of chemotherapy against death, the concept of palliative care has faded away as chemotherapies that aim to provide a “cure” have emerged. 8 Therefore, tumour features have been targeted using novel anticancer therapies. This approach has resulted in an increase in treatment options in recent years due to the rapid development pace of surgery, radiotherapy but mainly genomics, immune cell therapies, and other so-called personalized therapies, 9 such as immunotherapy, gene therapy, chimeric antigen receptor (CAR) T-cell therapy, 10 and mRNA vaccines. 11 Additionally, researchers have been looking for new and efficient therapies that can alleviate critical side effects caused by conventional treatments. These advanced basic and applied innovative cancer therapies illustrate the translational research that underlies the development of these treatments. 12 However, this research is not restricted to advanced areas with vast technologies; for example, in paediatrics, treatment innovation also includes for some authors improved formulation development with respect to palatability and manufacturing. 13 Thus, biotechnological innovation, which is measured based on the target’s novelty (first-in-class vs. advance-in-class vs. addition-to-class), may differ from the novelty of mechanisms of action and indications that may be considered clinical innovations. 14 Indeed, innovative treatments could provide new ways to put into practice what is known to be efficacious and enable access to effective interventions that provide the most meaningful benefit for patients. 15 In addition to the definition of innovation, there has been a growing debate on how to evaluate innovation. There is a constant goal or pressure of decreasing the development timelines of treatments through innovative trial designs. In the USA and Europe, accelerated approval processes have been developed, thus enabling rapid access to innovations across a wide range of indications, notably for oncology patients. In France, the number of patients with cancer who were treated with new drugs provided within early access programs increased substantially from 3,137 patients in 2019 to 18,341 in 2022, thus yielding a 484% increase. 16 However, it remains unclear whether patients benefit from these innovations. A previous review examined survival data from 95 cancer drugs granted based on immature data; a significant benefit was only observed for one-third of these indications. 17 Thus, the real benefit of innovation achieved by newly approved agents is unclear. Innovation in health technologies can be defined and measured in numerous ways, as illustrated by a recent literature review focusing on the utilization of innovation for health technology assessments (HTAs) across Europe. While severity, unmet need and therapeutic added value can be used to evaluate the degree of innovation in France, Japan and Italy, the criteria are different in England and Spain. 18 In contrast, oncologists perceived innovation as an evolving approach requiring adaptability and modularity based on the different medicines and different pathologies, although improving survival appears to be a widespread goal. 19 We hypothesized that the meaning of innovative treatment and the specific ways in which innovation is evaluated may depend on the perspective (i.e., physicians facing individual patients, or HTA bodies facing public health requirements). Therefore, we aimed to collect the opinions of the scientific and HTA communities regarding therapeutic innovations. Materials and Methods We performed a cross-sectional study using an online questionnaire. The questionnaire used in our study was developed for this study (Supplementary materials). It included 55 items and was administered to healthcare professionals through the Research Electronic Data Capture (RedCap https://www.project-redcap.org) platform. The items assessed the individual characteristics of the respondents (11 items) and their agreement/opinions with statements about innovation (44 items), including their opinions regarding the definition of innovation (5 items), their perception of innovation (12 items), the need for innovation (8 items), the development of innovations (8 items), the use of preclinical data to evaluate innovation (4 items) and the use of clinical data to evaluate innovation (7 items) . All opinions were scored using an 11-point Likert scale ranging from 0 (strongly disagree) to 10 (strongly agree), except the 5 items about the definition of innovation (3 open-ended items and 2 closed-ended items), the 4 items about preclinical data (items were scored on a 4-point Likert scale), and one open-ended question about methods to improve the development of innovation. Participants were recruited from the French Society for Oncology, the French Society for Haematology, the French Association of Clinical Pharmacology and Therapeutics, and the French Health Technology Assessment (HTA) body. Members of these organizations were recruited via email to complete this electronic questionnaire anonymously. The following summary statistics were computed: median [IQR], absolute frequencies and percentages. Opinions were divided into three categories: agreement (scores of 6 to 10 on the Likert scales), disagreement (scores of 0 to 4 on the Likert scales) and indifference (scores of 5 on the Likert Scales). Text analysis and representation via word clouds were used for open-ended questions. The respondents were divided into two groups according to their profile: oncology or health authority. Comparisons of the two groups were performed via the nonparametric Wilcoxon rank-sum test and the Fisher exact test. We then looked for features of the whole group of respondents based on the variables measured on the Likert scales. To assess overall links between the responses in each setting, principal component analysis (PCA) was performed. Missing data were first imputed via the iterative PCA algorithm (corresponding to an expectation-maximisation (EM) algorithm), and the number of components used in the algorithm was determined via cross-validation. Partitioning clustering with the k-means method was then applied, with the number of clusters determined via the elbow method. Statistical analyses were performed in R (https://www.R-project.org/) using the wordcloud, FactoMineR and missMDA packages. Ethics approval and consent to participate - All experiments were performed in accordance with relevant guidelines and regulations: The need of ethics approval was deemed unnecessary according to French regulations that indeed requires an ethics committee only for research on patients (according to the Law no. 78-17 of 6 January 1978 on data processing, data files and individual liberties). Informed consent to participate was obtained from all of the participants in the study. Results This study included 114 participants, with a median age of 45.5 years (IQR, 38-58). There were 55 (48%) women. The participants completed the questionnaire between April 11, 2024, and June 12, 2024. Among the respondents, there were 73 (64%) physicians (including 15 haematologists), and 22 (19%) pharmacists. Specifically, 77.2% (n= 88) of the participants were physicians (n=69), pharmacists (n=7) or other personnel involved in the planning, performance, or analysis of clinical trials (n=12), whereas 22.8% (n=26) of the participants were employees of national agencies who were in charge of treatment evaluation. Table 1 summarizes the respondents’ characteristics, including differences in age, sex, and profession across the two groups. Among the oncology group, 18 participants reported belonging to an institutional cooperative group in oncology, 75 participants reported playing a role in clinical trials (61 reported being investigators, and 45 reported conflicts of interest) (supplementary materials Table S1). Figure 1 displays the synonyms for “innovation” used by the respondents. Three main synonyms or related words emerged: “novelty”, “progress”, and “improvement”. Interestingly, there were some differences in the later ranks of related words across the groups, with the oncology group reporting “survival” and “revolution” as synonyms, while the health authority group reported “breakthrough” and “cure” as synonyms (supplementary Table S2). Both groups identified innovations such as CAR T-cell therapy as innovations. The oncology group also identified antibodies (either bispecific or not), whereas the health authority group highlighted specific antiviral drugs against hepatitis C virus (HCV). When considering how to identify an innovation, one half of both groups agreed that innovations propose a new mechanism of action, and almost all participants agreed that innovations must yield clinical improvements and a risk‒benefit ratio for the patient. However, there were significant differences between the oncology group and the health authority group in terms of innovations being based on new concepts (81% vs. 59%, respectively) (p=0.029), innovations requiring creativity (85% vs. 62%, respectively) (p=0.033), innovations being based on new models (71% vs. 55%, respectively) (p=0.052), and innovations benefiting from artificial intelligence and big data (61% vs. 38%, respectively) (p=0.025) (Figure 2). With respect to medical settings that especially need innovations, most participants in the oncology and health authority groups agreed that innovations may apply to all diseases (91% vs. 90%, respectively) and that all diseases could benefit from innovations (89% vs. 85%, respectively). There was a difference in terms of the interest in innovations within paediatrics, which was considered a priority for 75% of the respondents in the health authority group and 54%of respondents in the oncology group (p=0.046). We also examined on the development of innovations. Most respondents agreed that the development of innovations is costly (87%), that the development of innovations benefit from institutional research (79%), is booming (75%), is a long process (70%), relies on firms (68%), is risky (62%), and is possibly too costly (57%) (Supplementary Figure S1). The main differences between the groups concerned the data required at the time of evaluation of an innovation (Figure 3). The groups indeed disagreed on the need for any randomized clinical trial (RCT), with 49% of the oncology group and only 20% of the health authority group agreeing that the evaluation of an innovation does not require data from an RCT (p=0.012). Furthermore, 12% of the oncology group and only 5% of the health authority group agreed that that the accelerated grant of an innovation does not require any clinical data (p=0.017). Similarly, the median agreement value on the Likert scale regarding the need to simplify the rules of evaluation for innovation was 2 (IQR, 1-3.25) for the health authority group and 6 (IQR, 4.5-8) for the oncology group (<0.0001). Based on these opinions, three clusters of responses could be identified (Supplementary Figure S2), with clusters 1 and 3 clashing in terms of the level of agreement regarding the evaluation process of innovation, whereas cluster 2 was mostly related to obtaining data on mechanisms or pharmacological data, independent of the evaluation process (as indicated by the right angle formed by the variables). Furthermore, the clusters differed in terms of agreement regarding the simplification of the process of evaluating innovations (ranging from a median of 2 points in cluster 1, 5 in cluster 2, up to 7 in cluster 3) (p<0.0001), evaluating innovations without data from an RCT (with medians of 2, 4 and 7, respectively) (p<0.0001), and evaluating innovations without clinical data (median of 0, 2 and 2, respectively) (p=0.0005). Such an opposition was also exemplified regarding the potential benefit of evaluating innovations using artificial intelligence and big data (median of 4, 6.5 and 7) (p<0.0001). In contrast, as noted above, cluster 2 appears somewhat unclear regarding those points, with median values of agreement ranging from 4-5; this finding could be due to less experience among the respondents, as the median age was 39 years in cluster 2, 46.5 in cluster 1 and 53.5 in cluster 3. As expected, the proportion of respondents from the oncology group increased from 48% in cluster 1, 65% in cluster 2, 100% in cluster 3 (p<0.0001). Discussion In this paper, we focused on “innovation” in the cancer setting, including practitioners who interact with cancer patients and members of health technology assessment bodies. Our study aimed to explore the perceptions among practitioners—more than 90% of whom have participated in clinical trials—and among members of health agencies regarding the meaning, needs, and evaluation of therapeutic innovation for cancer patients. There was a consensus regarding the associations of innovation with the concepts of novelty, advance, and improvement. However, although most of the respondents agreed on the potential benefit of innovative drugs in all oncology settings, there was a discrepancy regarding how innovative drugs should be evaluated. Indeed, the group of oncologists widely approved the need for simplified evaluations, including evaluations without data from RCTs or without clinical data. This contrasted with that of health authority members, who expect similar rules of evaluation across all drugs and stressed the need for evidence. These findings indicate that the two groups, both of which targeting patient's interest, do not have similar standards of evidence-based medicine or similar opinions on evaluating innovations. 20 This may also rely on differences in pressures, from the patients and the pharmaceutical industrials lobbying in the former, and from the need to control healthcare expenditures in the later. Unfortunately, there is little true dialogue between these groups, and their disagreements are highlighted in the tribune columns of newspapers. 21 Indeed, while professionals charged with decision-making typically require evidence regarding the safety and efficacy of new drugs, prescribers and patients may not require definitive evidence of efficacy. 22 Enabling rapid access to innovations while maintaining an acceptable level of quality is crucial, and increasing competency in these areas is necessary. However, while there is a consensus regarding the need to appraise mechanistic reasoning in medicine, there is no widely accepted view on how to amalgamate evidence of different types. Ultimately, beyond the scientific claims and promises of efficacy put forwards by some, the community, the healthcare system, and, of course, patients cannot be satisfied with promises or false hopes from an ethics viewpoint. We must ensure that the efficacy of innovations has been proven and that they exhibit sufficient safety, in line with recent reviews of FDA accelerated approvals. 14,23,24 Conditional approvals should be more often used, with clear rules to their ends in terms of futility or benefit for the patients. Drugs and technologies are important but make little difference in a health system that is insensitive to the needs of individuals and communities. 25 Although new drugs, diagnostics, and technologies are important, they are not what patients with cancer always need. A multidisciplinary and holistic approach to optimize patient outcomes and quality of life is highly important, especially in situations where survival is prolonged due to therapeutic advances such as chronic lymphocytic leukaemia. 26 Moreover, significant disparities in access to innovative care have been reported worldwide, for instance, in breast cancer; 27 these disparities should be addressed to improve timely access to innovative treatments for all patients. Our study has several limitations. First, we focused on the innovation in drugs. However, oncology is renowned for leading innovation in research and in care, including aspects of prevention, screening, 28 symptomatic detection, cancer management palliative care, digital pathology radiology, and other technological breakthroughs related to surgery, and radiotherapy. 29,30 Second, the sample size was somewhat small, especially in the health authority group. However, this discrepancy is likely related to the size of the two broader populations. Finally, our study was restricted to France, and the findings cannot be generalized to other countries. Nevertheless, this is the first attempt to collect opinions from members of the broader health community who are involved in such innovative therapies. Further studies should be conducted. In summary, the perception of innovation in cancer treatment was related to the concepts of novelty, advance, and improvement. There were considerable discrepancies regarding the evidence needed to evaluate or approve innovations in order to enable early access but then potentially to withdraw the unconfirmed ones. A multidisciplinary approach to sequentially or conditionally merge and quantify - rather than oppose - different types of evidence, including evidence related to patient quality of life, should be developed. Abbreviations CAR, chimeric antigen receptor EM, expectation-maximisation HCV, hepatitis C virus HTA, Health Technology Assessment IQR, interquartile range PCA, principal component analysis USA, Unites States of America Declarations Ethics approval and consent to participate - The need of ethics approval was deemed unnecessary according to French regulations that indeed requires an ethics committee only for research on patients (according to the Law no. 78-17 of 6 January 1978 on data processing, data files and individual liberties) Consent for publication – ‘Not applicable’ Availability of data and materials - All data used in this study can be accessed upon request to the first author. The questionnaire used in your study was developed for this study and has not previously been published elsewhere Competing Interests - All authors declare no competing interests. Funding - None Authors' contributions - SC and VL conceptualised and designed the study, accessed the raw data, acquired, verified all the data in the study, analysed the data, and drafted the manuscript. XT, CM and authors interpreted the data, critically revised the manuscript. All authors had access to the raw data and accept responsibility for the decision to submit for publication. Acknowledgements - The authors would like to thank all respondents of this online survey. The authors would like to thank all respondents of this online survey. We also wish to warmly thank the Pr André Baruchel for his helpful comments and suggestions on the manuscript. Availability of data and materials - Data are available upon request to the corresponding author. Data sharing All data used in this study can be accessed upon request to the first author. Declaration of interest All authors declare no competing interests. References United States. 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Available at: https://onlinelibrary.wiley.com/doi/10.1002/cai2.19 Tables Table 1 : Respondents’ characteristics according to group Health authority group N=26 Oncology group N=88 p value Age, years, median (IQR) 36.5 (32-42.75) 51 (40.25-59.75) < 0.0001 Female sex 18 (69%) 37 (42%) 0.024 Profession Physicians Including haematologists Pharmacists Others 4 (15%) 0/3 15 (58%) 7 (27%) 69 (78%) 15/86 (17%) 7 (8%) 12 (14%) <0.0001 IQR, interquartile range Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterials22nov24.docx CRF.pdf Cite Share Download PDF Status: Published Journal Publication published 22 Oct, 2025 Read the published version in BMC Cancer → Version 1 posted Editorial decision: Revision requested 08 May, 2025 Reviews received at journal 04 May, 2025 Reviewers agreed at journal 26 Apr, 2025 Reviewers agreed at journal 24 Apr, 2025 Reviewers invited by journal 24 Apr, 2025 Editor assigned by journal 22 Apr, 2025 Editor invited by journal 07 Apr, 2025 Submission checks completed at journal 07 Apr, 2025 First submitted to journal 07 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6350857","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":448295370,"identity":"9978da5d-0928-4d18-b006-d879771e0ee0","order_by":0,"name":"Sylvie Chevret","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEElEQVRIie2PMUsDMRTH3xHQRahjpCf3FVICdjn8LC8EzsXNxUEk5cAu9wHqtxCcnLxyUJeg64GD59K54nLDIT4p1HLwOgvmN+SRf/J7eQEIBP4kwgFSUetdui6UDHgl2lYw2yhHbpcCv0q1yVklmZkb2VxCMt4vTlYf7Ytxw3y5ajqQY8ZRNSnoYfRQeH07w1fj4oWmPiDjklGkyRVdQFVnVhyQ8lijBuPgWvKDkfJFytvSig6fjZNnn4A0GKdAbSYN9aRXRCUAS1LONeAeryj/PmlwIUd33lZRkVntYn8B9EFWSaa2nLdXaaKe5jm06emxG07vo7ZL+cEO8WfdPpbQT3oMyn6y43IgEAj8T74BNxxZ0Ib+n2YAAAAASUVORK5CYII=","orcid":"","institution":"ECSTRRA, UMR1342, Inserm, Paris Cité University","correspondingAuthor":true,"prefix":"","firstName":"Sylvie","middleName":"","lastName":"Chevret","suffix":""},{"id":448295373,"identity":"58e0ad46-07c6-4dcf-80ac-41edd9eeee92","order_by":1,"name":"Xavier Troussard","email":"","orcid":"","institution":"Hématologie, CHU Caen Normandie","correspondingAuthor":false,"prefix":"","firstName":"Xavier","middleName":"","lastName":"Troussard","suffix":""},{"id":448295375,"identity":"ea857594-f87c-446e-aa33-b3f9fb8613cb","order_by":2,"name":"Charlotte Masia","email":"","orcid":"","institution":"Service d'Evaluation des Médicaments, Haute Autorité de Santé","correspondingAuthor":false,"prefix":"","firstName":"Charlotte","middleName":"","lastName":"Masia","suffix":""},{"id":448295376,"identity":"919f5035-2cf5-4fb2-9d6a-cc170c2132f4","order_by":3,"name":"Pierre Cochat","email":"","orcid":"","institution":"Service d'Evaluation des Médicaments, Haute Autorité de Santé","correspondingAuthor":false,"prefix":"","firstName":"Pierre","middleName":"","lastName":"Cochat","suffix":""},{"id":448295377,"identity":"6885603c-42a7-4a68-bfe7-29107e0e2703","order_by":4,"name":"Vincent Levy","email":"","orcid":"","institution":"ECSTRRA, UMR1342, Inserm, Paris Cité University","correspondingAuthor":false,"prefix":"","firstName":"Vincent","middleName":"","lastName":"Levy","suffix":""}],"badges":[],"createdAt":"2025-04-01 08:08:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6350857/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6350857/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-025-14922-2","type":"published","date":"2025-10-22T16:16:07+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82119967,"identity":"edf87b82-7aa2-4835-8595-ade23823d173","added_by":"auto","created_at":"2025-05-07 03:12:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1403514,"visible":true,"origin":"","legend":"\u003cp\u003eWord cloud of synonyms and related words for innovation in both groups (Fig. 1A Oncology group; Fig. 1B Health authority group)\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-6350857/v1/a3c77a8ad3e38f573bc08cc1.png"},{"id":82120837,"identity":"c33edb84-0a77-4044-b31b-309b8aa8ba3c","added_by":"auto","created_at":"2025-05-07 03:20:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":280325,"visible":true,"origin":"","legend":"\u003cp\u003eLikert scale of innovation perception according to the group (left: Oncology, right: Health Authorities)- Each bar represents the distribution of respondent agreement level on the item, ranging from 0 (full disagreement) to 10 (full agreement); percentage of disagreement (from 0 to 4) are reported on the left side, while percentage of agreement (from 6 to 10) are reported on the right side of the plot, with indecision percentage (that is, coted 5 on the scale) are reported on the grey middle zone of the bar. For instance, 46% of the Oncology group agreed with the fact that Innovation may concern new indication, versus 34% who did not agree and 21% who were indecisive.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-6350857/v1/951df7f29b353d8b84a59e55.png"},{"id":82119969,"identity":"b297c5c0-d39a-4a09-8c81-e7d86a78e2fc","added_by":"auto","created_at":"2025-05-07 03:12:41","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":214184,"visible":true,"origin":"","legend":"\u003cp\u003eLikert of respondents’ opinion regarding data needed for evaluation of innovation according to the group (left: Oncology, right: Health Authorities). Each bar represents the distribution of respondent agreement level on the item, ranging from 0 (full disagreement) to 10 (full agreement); percentage of disagreement (from 0 to 4) are reported on the left side, while percentage of agreement (from 6 to 10) are reported on the right side of the plot, with indecision percentage (that is, coted 5 on the scale) are reported on the grey middle zone of the bar\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-6350857/v1/9a6eb029f231a1438b4f1fc6.png"},{"id":94490386,"identity":"2335b824-1aa2-497e-85bc-ad2f52e4c4d4","added_by":"auto","created_at":"2025-10-27 17:09:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2160309,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6350857/v1/4198233b-f324-4052-bb0d-5bb9bfb30d29.pdf"},{"id":82119973,"identity":"33a36321-159f-4eab-8519-7c7805922cce","added_by":"auto","created_at":"2025-05-07 03:12:41","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":450175,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials22nov24.docx","url":"https://assets-eu.researchsquare.com/files/rs-6350857/v1/0517b6704b7110c5a9e8d919.docx"},{"id":82119968,"identity":"3acd8af3-a59a-4cc2-9b17-0b0105538d6e","added_by":"auto","created_at":"2025-05-07 03:12:41","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":53326,"visible":true,"origin":"","legend":"","description":"","filename":"CRF.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6350857/v1/159fb55050048ba0d06c13a1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Therapeutic innovation in oncology: What do you mean? What we cannot talk about, we must keep silent. L. Wittgenstein","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAlmost one-half century ago, “innovative” treatments were defined as treatments that “depart in a significant way from standard or accepted practice”.\u003csup\u003e1\u003c/sup\u003e Currently, the terms “innovation” and “innovative” are buzzwords that are widely used in many different fields, including health care.\u003csup\u003e2\u003c/sup\u003e The Collins dictionary defines innovation as the introduction of new ideas, methods, or things. Innovation has then been seen as the initial implementation of a new idea as well as the economic optimization of knowledge utilization.\u003csup\u003e2\u003c/sup\u003e However, there is no comprehensive and generally accepted definition of this term,\u0026nbsp;and different disciplines use various definitions for innovation. This is particularly true in oncology, where any evidence of new mechanisms or technology is considered to be an innovation that should be widely applied by physicians and administered to the public,\u003csup\u003e3\u003c/sup\u003e which stands\u0026nbsp;in contrast with\u0026nbsp;more precautious, evidence-based decision-making in public health agencies.\u003csup\u003e4\u003c/sup\u003e This likely relies on considerable\u0026nbsp;expectations\u0026nbsp;for unmet medical needs, to have something to “offer\" to the patient, with increasing difficulty in accepting therapeutic abstention,\u0026nbsp;while\u0026nbsp;ensuring patient safety.\u003csup\u003e5\u003c/sup\u003e Indeed, cancer remains a main burden, with\u0026nbsp;increasing\u0026nbsp;incidence and prevalence,\u0026nbsp;and it is\u0026nbsp;responsible for millions of deaths, thus highlighting\u0026nbsp;the need for more effective treatments for patients.\u003csup\u003e6\u003c/sup\u003e This was recently emphasized by the fact that in 2022, adolescents and young adults accounted for more than 12,000 cancer-related deaths in Europe.\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn the history of oncology, there is has been a tangled relationship between innovation, “cure,” and death: while palliative measures first summarized the overall fight of chemotherapy against death, the concept of palliative care has faded away as chemotherapies that aim to provide a “cure” have emerged.\u003csup\u003e8\u003c/sup\u003e Therefore, tumour features have been targeted using novel anticancer therapies. This approach has resulted in an increase in treatment options in recent years due to the rapid development pace of surgery, radiotherapy but mainly genomics, immune cell therapies, and other so-called personalized therapies,\u003csup\u003e9\u003c/sup\u003e such as immunotherapy, gene therapy,\u0026nbsp;chimeric antigen receptor (CAR) T-cell therapy,\u003csup\u003e10\u003c/sup\u003e and\u0026nbsp;mRNA vaccines.\u003csup\u003e11\u003c/sup\u003e Additionally, researchers have been looking for new and efficient therapies\u0026nbsp;that\u0026nbsp;can alleviate critical side effects caused by conventional treatments. These advanced basic and applied innovative\u0026nbsp;cancer\u0026nbsp;therapies illustrate the translational research that underlies the development of these treatments.\u003csup\u003e12\u003c/sup\u003e However, this research is not restricted to advanced areas with vast technologies; for example, in paediatrics, treatment innovation also\u0026nbsp;includes for some authors\u0026nbsp;improved formulation development with respect to palatability and manufacturing.\u003csup\u003e13\u003c/sup\u003e Thus, biotechnological innovation, which is measured based on the target’s novelty (first-in-class vs. advance-in-class vs. addition-to-class),\u0026nbsp;may differ from the novelty of mechanisms of action and indications that may be considered clinical innovations.\u003csup\u003e14\u003c/sup\u003e Indeed, innovative treatments could\u0026nbsp;provide\u0026nbsp;new ways to put into practice what is known to be efficacious and\u0026nbsp;enable\u0026nbsp;access to effective interventions that\u0026nbsp;provide\u0026nbsp;the most meaningful benefit for patients.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn addition to the definition of innovation, there has been a growing debate on how to evaluate innovation. There is a constant goal or pressure of\u0026nbsp;decreasing the development timelines of treatments through innovative trial designs. In\u0026nbsp;the\u0026nbsp;USA and Europe, accelerated approval processes have been developed, thus enabling rapid access to innovations across a wide range of indications, notably for oncology patients. In France, the\u0026nbsp;number of patients with cancer who were treated with new drugs provided within early access\u0026nbsp;programs increased substantially\u0026nbsp;from 3,137 patients in 2019 to 18,341 in 2022, thus yielding a 484% increase.\u003csup\u003e16\u003c/sup\u003e However, it remains unclear whether patients benefit from these\u0026nbsp;innovations. A previous review examined survival data from 95 cancer drugs granted based on immature data; a significant benefit was only observed for one-third of these indications.\u003csup\u003e17\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThus, the real benefit of innovation achieved by newly approved agents is unclear. Innovation in health technologies can be defined and measured in numerous ways, as illustrated by a recent literature review focusing on the utilization of innovation for health technology assessments (HTAs) across Europe. While severity, unmet need and therapeutic added value can be used to evaluate the degree of innovation in France, Japan and Italy, the criteria are different in England and Spain.\u003csup\u003e18\u003c/sup\u003e In contrast, oncologists perceived innovation as an evolving approach requiring adaptability and modularity based on the different medicines and different pathologies,\u0026nbsp;although\u0026nbsp;improving survival appears\u0026nbsp;to be\u0026nbsp;a widespread goal.\u003csup\u003e19\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eWe hypothesized that the meaning of innovative treatment and the specific ways in which innovation is evaluated may depend on the perspective (i.e., physicians facing individual patients, or HTA bodies facing public health requirements). Therefore, we aimed to collect the opinions of the scientific and HTA communities regarding therapeutic innovations.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eWe performed a cross-sectional study using an online questionnaire. The questionnaire used in our study was developed for this study (Supplementary materials). It included 55 items and was administered to healthcare professionals through the Research Electronic Data Capture (RedCap https://www.project-redcap.org) platform. The items assessed the individual characteristics of the respondents (11 items) and their agreement/opinions with statements about innovation (44 items), including their opinions regarding the definition of innovation (5 items), their perception of innovation (12 items), the need for innovation (8 items), the development of innovations (8 items), the use of preclinical data to evaluate innovation (4 items) and the use of clinical data to evaluate innovation (7 items) . All opinions were scored using an 11-point Likert scale ranging from 0 (strongly disagree) to 10 (strongly agree), except the 5 items about the definition of innovation (3 open-ended items and 2 closed-ended items), the 4 items about preclinical data (items were scored on a 4-point Likert scale), and one open-ended question about methods to improve the development of innovation.\u003c/p\u003e\n\u003cp\u003eParticipants were recruited from the French Society for Oncology, the French Society for Haematology, the French Association of Clinical Pharmacology and Therapeutics, and the French Health Technology Assessment (HTA) body. Members of these organizations were recruited via email to complete this electronic questionnaire anonymously.\u003c/p\u003e\n\u003cp\u003eThe following summary statistics were computed: median [IQR], absolute frequencies and percentages. Opinions were divided into three categories: agreement (scores of 6 to 10 on the Likert scales), disagreement (scores of 0 to 4 on the Likert scales) and indifference (scores of 5 on the Likert Scales). Text analysis and representation via word clouds were used for open-ended questions.\u003c/p\u003e\n\u003cp\u003eThe respondents were divided into two groups according to their profile: oncology or health authority. Comparisons of the two groups were performed via the nonparametric Wilcoxon rank-sum test and the Fisher exact test. We then looked for features of the whole group of respondents based on the variables measured on the Likert scales. To assess overall links between the responses in each setting, principal component analysis (PCA) was performed. Missing data were first imputed via\u0026nbsp;the iterative PCA algorithm (corresponding to an expectation-maximisation (EM) algorithm), and\u0026nbsp;the\u0026nbsp;number of components used in the algorithm was determined\u0026nbsp;via\u0026nbsp;cross-validation. Partitioning clustering with the k-means method was then applied, with\u0026nbsp;the\u0026nbsp;number of clusters determined\u0026nbsp;via\u0026nbsp;the elbow method.\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed in R (https://www.R-project.org/)\u0026nbsp;using the wordcloud, FactoMineR and\u0026nbsp;missMDA packages.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate -\u0026nbsp;\u003c/strong\u003eAll experiments were performed in accordance with relevant guidelines and regulations: The need of ethics approval was deemed unnecessary according to French regulations that indeed requires an ethics committee only for research on patients (according to the Law no. 78-17 of 6 January 1978 on data processing, data files and individual liberties). Informed consent to participate was obtained from all of the participants in the study.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThis study included 114 participants, with a median age of 45.5 years (IQR, 38-58). There were 55 (48%) women. The participants completed the questionnaire between April 11, 2024, and June 12, 2024. Among the respondents, there were 73 (64%) physicians (including 15 haematologists), and 22 (19%) pharmacists. Specifically, 77.2% (n= 88) of the participants were physicians (n=69), pharmacists (n=7) or other personnel involved in the planning, performance, or analysis of clinical trials (n=12), whereas 22.8% (n=26) of the participants were employees of national agencies who were in charge of treatment evaluation. Table 1 summarizes the respondents’ characteristics, including differences in age, sex, and profession across the two groups. Among the oncology group, 18 participants reported belonging to an institutional cooperative group in oncology, 75 participants reported playing a role in clinical trials (61 reported being investigators, and 45 reported conflicts of interest) (supplementary materials Table S1).\u003c/p\u003e\n\u003cp\u003eFigure 1 displays the synonyms for “innovation” used by the respondents. Three main synonyms or related words emerged: “novelty”, “progress”, and “improvement”. Interestingly, there were some differences in the later ranks of related words across the groups, with the oncology group reporting “survival” and “revolution” as synonyms, while the health authority group reported “breakthrough” and “cure” as synonyms (supplementary Table S2). Both groups identified innovations such as CAR T-cell therapy as innovations. The oncology group also identified antibodies (either bispecific or not), whereas the health authority group highlighted specific antiviral drugs against hepatitis C virus (HCV).\u003c/p\u003e\n\u003cp\u003eWhen considering how to identify an innovation, one half of both groups agreed that innovations propose a new mechanism of action, and almost all participants agreed that innovations must yield clinical improvements and a risk‒benefit ratio for the patient. However, there were significant differences between the oncology group and the health authority group in terms of innovations being based on new concepts (81% vs. 59%, respectively) (p=0.029), innovations requiring creativity (85% vs. 62%, respectively) (p=0.033), innovations being based on new models (71% vs. 55%, respectively) (p=0.052), and innovations benefiting from artificial intelligence and big data (61% vs. 38%, respectively) (p=0.025) (Figure 2).\u003c/p\u003e\n\u003cp\u003eWith respect to medical settings that especially need innovations, most participants in the oncology and health authority groups agreed that innovations may apply to all diseases (91% vs. 90%, respectively) and that all diseases could benefit from innovations (89% vs. 85%, respectively). There was a difference in terms of the interest in innovations within paediatrics, which was considered a priority for 75% of the respondents in the health authority group and 54%of respondents in the oncology group (p=0.046).\u003c/p\u003e\n\u003cp\u003eWe also examined on the development of innovations. Most respondents agreed that the development of innovations is costly (87%), that the development of innovations benefit from institutional research (79%), is booming (75%), is a long process (70%), relies on firms (68%), is risky (62%), and is possibly too costly (57%) (Supplementary Figure S1). The main differences between the groups concerned the data required at the time of evaluation of an innovation (Figure 3). The groups indeed disagreed on the need for any randomized clinical trial (RCT), with 49% of the oncology group and only 20% of the health authority group agreeing that the evaluation of an innovation does not require data from an RCT (p=0.012). Furthermore, 12% of the oncology group and only 5% of the health authority group agreed that that the accelerated grant of an innovation does not require any clinical data (p=0.017). Similarly, the median agreement value on the Likert scale regarding the need to simplify the rules of evaluation for innovation was 2 (IQR, 1-3.25) for the health authority group and 6 (IQR, 4.5-8) for the oncology group (\u0026lt;0.0001).\u003c/p\u003e\n\u003cp\u003eBased on these opinions, three clusters of responses could be identified (Supplementary Figure S2), with clusters 1 and 3 clashing in terms of the level of agreement regarding the evaluation process of innovation, whereas cluster 2 was mostly related to obtaining data on mechanisms or pharmacological data, independent of the evaluation process (as indicated by the right angle formed by the variables). Furthermore, the clusters differed in terms of agreement regarding the simplification of the process of evaluating innovations (ranging from a median of 2 points in cluster 1, 5 in cluster 2, up to 7 in cluster 3) (p\u0026lt;0.0001), evaluating innovations without data from an RCT (with medians of 2, 4 and 7, respectively) (p\u0026lt;0.0001), and evaluating innovations without clinical data (median of 0, 2 and 2, respectively) (p=0.0005). Such an opposition was also exemplified regarding the potential benefit of evaluating innovations using artificial intelligence and big data (median of 4, 6.5 and 7) (p\u0026lt;0.0001). In contrast, as noted above, cluster 2 appears somewhat unclear regarding those points, with median values of agreement ranging from 4-5; this finding could be due to less experience among the respondents, as the median age was 39 years in cluster 2, 46.5 in cluster 1 and 53.5 in cluster 3. As expected, the proportion of respondents from the oncology group increased from 48% in cluster 1, 65% in cluster 2, 100% in cluster 3 (p\u0026lt;0.0001).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this paper, we focused on “innovation” in the cancer setting, including practitioners who interact with cancer patients and members of health technology assessment bodies. Our study aimed to explore the perceptions among practitioners—more than 90% of whom have participated in clinical trials—and among members of health agencies regarding the meaning, needs, and evaluation of therapeutic innovation for cancer patients. There was a consensus regarding the associations of innovation with the concepts of novelty, advance, and improvement. However, although most of the respondents agreed on the potential benefit of innovative drugs in all oncology settings, there was a discrepancy regarding how innovative drugs should be evaluated. Indeed, the group of oncologists widely approved the need for simplified evaluations, including evaluations without data from RCTs or without clinical data. This contrasted with that of health authority members, who expect similar rules of evaluation across all drugs and stressed the need for evidence. These findings indicate that the two groups, both of which targeting patient's interest, do not have similar standards of evidence-based medicine or similar opinions on evaluating innovations.\u003csup\u003e20\u003c/sup\u003e This may also rely on differences in pressures, from the patients and the pharmaceutical industrials lobbying in the former, and from the need to control healthcare expenditures in the later. Unfortunately, there is little true dialogue between these groups, and their disagreements are highlighted in the tribune columns of newspapers.\u003csup\u003e21\u003c/sup\u003e Indeed, while professionals charged with decision-making typically require evidence regarding the safety and efficacy of new drugs, prescribers and patients may not require definitive evidence of efficacy.\u003csup\u003e22\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eEnabling rapid access to innovations while maintaining an acceptable level of quality is crucial, and increasing competency in these areas is necessary. However, while there is a consensus regarding the need to appraise mechanistic reasoning in medicine, there is no widely accepted view on how to amalgamate evidence of different types. Ultimately, beyond the scientific claims and promises of efficacy put forwards by some, the community, the healthcare system, and, of course, patients cannot be satisfied with promises or false hopes from an ethics viewpoint. We must ensure that the efficacy of innovations has been proven and that they exhibit sufficient safety, in line with recent reviews of FDA accelerated approvals.\u003csup\u003e14,23,24\u003c/sup\u003e Conditional approvals should be more often used, with clear rules to their ends in terms of futility or benefit for the patients.\u003c/p\u003e\n\u003cp\u003eDrugs and technologies are important but make little difference in a health system that is insensitive to the needs of individuals and communities.\u003csup\u003e25\u003c/sup\u003e Although new drugs, diagnostics, and technologies are important, they are not what patients with cancer always need. A multidisciplinary and holistic approach to optimize patient outcomes and quality of life is highly important, especially in situations where survival is prolonged due to therapeutic advances such as chronic lymphocytic leukaemia.\u003csup\u003e26\u003c/sup\u003e Moreover, significant disparities in access to innovative care have been reported worldwide, for instance,\u0026nbsp;in breast cancer;\u003csup\u003e27\u003c/sup\u003e these disparities should be addressed\u0026nbsp;to improve timely access to innovative treatments\u0026nbsp;for\u0026nbsp;all patients.\u003c/p\u003e\n\u003cp\u003eOur study has several limitations. First, we focused on the innovation in drugs. However, oncology is renowned for leading innovation in research and in care, including aspects of prevention, screening,\u003csup\u003e28\u003c/sup\u003e symptomatic detection, cancer management palliative care, digital pathology radiology, and other technological\u0026nbsp;breakthroughs\u0026nbsp;related to surgery, and radiotherapy.\u003csup\u003e29,30\u003c/sup\u003e Second, the sample size was somewhat\u0026nbsp;small, especially in the\u0026nbsp;health\u0026nbsp;authority\u0026nbsp;group. However, this discrepancy is likely related to the size of the two broader populations.\u0026nbsp;Finally, our study was restricted to France, and\u0026nbsp;the\u0026nbsp;findings\u0026nbsp;cannot\u0026nbsp;be generalized to other countries. Nevertheless, this is the first attempt to collect\u0026nbsp;opinions\u0026nbsp;from members of the broader health community who are involved in such innovative therapies. Further studies should be conducted.\u003c/p\u003e\n\u003cp\u003eIn summary, the perception of innovation in cancer treatment was related to the concepts of novelty, advance, and improvement. There were considerable discrepancies regarding the evidence needed to evaluate or approve innovations in order to enable early access but then potentially to withdraw the unconfirmed ones. A multidisciplinary approach to sequentially or conditionally merge and quantify - rather than oppose - different types of evidence, including evidence related to patient quality of life, should be developed.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCAR, chimeric antigen receptor\u003c/p\u003e\n\u003cp\u003eEM, expectation-maximisation\u003c/p\u003e\n\u003cp\u003eHCV, hepatitis C virus\u003c/p\u003e\n\u003cp\u003eHTA, Health Technology Assessment\u003c/p\u003e\n\u003cp\u003eIQR, interquartile range\u003c/p\u003e\n\u003cp\u003ePCA, principal component analysis\u003c/p\u003e\n\u003cp\u003eUSA, Unites States of America\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate -\u0026nbsp;\u003c/strong\u003eThe need of ethics approval was deemed unnecessary according to French regulations that indeed requires an ethics committee only for research on patients (according to the Law no. 78-17 of 6 January 1978 on data processing, data files and individual liberties)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication \u0026ndash;\u0026nbsp;\u003c/strong\u003e\u0026lsquo;Not applicable\u0026rsquo;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials -\u0026nbsp;\u003c/strong\u003eAll data used in this study can be accessed upon request to the first author. The questionnaire used in your study was developed for this study and has not previously been published elsewhere\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests -\u0026nbsp;\u003c/strong\u003eAll authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e- None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions -\u0026nbsp;\u003c/strong\u003eSC and VL conceptualised and designed the study, accessed the raw data, acquired, verified all the data in the study, analysed the data, and drafted the manuscript. XT, CM and authors interpreted the data, critically revised the manuscript. All authors had access to the raw data and accept responsibility for the decision to submit for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements -\u0026nbsp;\u003c/strong\u003eThe authors would like to thank all respondents of this online survey.\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all respondents of this online survey. We also wish to warmly thank the Pr Andr\u0026eacute; Baruchel for his helpful comments and suggestions on the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials -\u003c/strong\u003e Data are available upon request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData sharing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data used in this study can be accessed upon request to the first author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eUnited States. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research [Internet]. CreateSpace Independent Publishing Platform 1978. Available at: https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html\u003c/li\u003e\n\u003cli\u003eFlessa S, Huebner C. Innovations in Health Care\u0026mdash;A Conceptual Framework. \u003cem\u003eInt J Environ Res Public Health\u003c/em\u003e. September 24, 2021 [cited June 14, 2024];18(19):10026. Available at: https://www.mdpi.com/1660-4601/18/19/10026\u003c/li\u003e\n\u003cli\u003eFundytus A, Sengar M, Lombe D, Hopman W, Jalink M, Gyawali B, et al. Access to cancer medicines deemed essential by oncologists in 82 countries: an international, cross-sectional survey. \u003cem\u003eLancet Oncol\u003c/em\u003e. October 2021 [cited July 5, 2024];22(10):1367\u0026ndash;1377. Available at: https://linkinghub.elsevier.com/retrieve/pii/S1470204521004630\u003c/li\u003e\n\u003cli\u003eMazzucca S, Jacob RR, Valko CA, Macchi M, Brownson RC. 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Cancer care: widening the scope of innovation. \u003cem\u003eThe Lancet\u003c/em\u003e. June 2022 [cited June 14, 2024];399(10344):2325. Available at: https://linkinghub.elsevier.com/retrieve/pii/S0140673622011345\u003c/li\u003e\n\u003cli\u003eMartin T, Rioufol C, Favier B, Martelli N, Madelaine I, Chouaid C, et al. Impact of Early Access Reform on Oncology Innovation in France: Approvals, Patients, and Costs. \u003cem\u003eBioDrugs\u003c/em\u003e. May 2024 [cited June 16, 2024];38(3):465\u0026ndash;475. Available at: https://link.springer.com/10.1007/s40259-024-00658-1\u003c/li\u003e\n\u003cli\u003eNaci H, Zhang Y, Woloshin S, Guan X, Xu Z, Wagner AK. Overall survival benefits of cancer drugs initially approved by the US Food and Drug Administration on the basis of immature survival data: a retrospective analysis. \u003cem\u003eLancet Oncol\u003c/em\u003e. June 2024 [cited July 5, 2024];25(6):760\u0026ndash;769. 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Who will challenge evidence-based medicine? \u003cem\u003eJ R Coll Physicians Lond\u003c/em\u003e. 1999;33(3):249\u0026ndash;251.\u003c/li\u003e\n\u003cli\u003eAvet-Loiseau H, Gillot, L. Les patients atteints de cancer doivent avoir acc\u0026egrave;s \u0026agrave; l\u0026rsquo;innovation th\u0026eacute;rapeutique. Le Monde March 3, 2023; Available at: https://www.lemonde.fr/sciences/article/2023/03/03/les-patients-atteints-de-cancer-doivent-avoir-acces-a-l-innovation-therapeutique_6164008_1650684.html\u003c/li\u003e\n\u003cli\u003eTilburt JC. Evidence‐based medicine beyond the bedside: keeping an eye on context. \u003cem\u003eJ Eval Clin Pract\u003c/em\u003e. October 2008 [cited July 5, 2024];14(5):721\u0026ndash;725. Available at: https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2753.2008.00948.x\u003c/li\u003e\n\u003cli\u003eBeakes-Read G, Neisser M, Frey P, Guarducci M. Analysis of FDA\u0026rsquo;s Accelerated Approval Program Performance December 1992\u0026ndash;December 2021. \u003cem\u003eTher Innov Regul Sci\u003c/em\u003e. September 2022 [cited March 12, 2024];56(5):698\u0026ndash;703. Available at: https://link.springer.com/10.1007/s43441-022-00430-z\u003c/li\u003e\n\u003cli\u003eRibeiro TB, Colunga-Lozano LE, Araujo APV, Bennett CL, Hozo I, Djulbegovic B. Single-arm clinical trials that supported FDA accelerated approvals have modest effect sizes and at high risk of bias. \u003cem\u003eJ Clin Epidemiol\u003c/em\u003e. January 2022 [cited June 7, 2022];S0895435622000257. Available at: https://linkinghub.elsevier.com/retrieve/pii/S0895435622000257\u003c/li\u003e\n\u003cli\u003eLancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. \u003cem\u003eLancet Haematol\u003c/em\u003e. July 2021;8(7):e481\u0026ndash;e491.\u003c/li\u003e\n\u003cli\u003eFedele PL, Opat S. Chronic Lymphocytic Leukemia: Time to Care for the Survivors. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. June 10, 2024 [cited July 5, 2024];42(17):2005\u0026ndash;2011. Available at: https://ascopubs.org/doi/10.1200/JCO.23.02738\u003c/li\u003e\n\u003cli\u003eIgnatiadis M, Poulakaki F, Spanic T, Brain E, Lacombe D, Sonke GS, et al. EBCC-14 manifesto: Addressing disparities in access to innovation for patients with metastatic breast cancer across Europe. \u003cem\u003eEur J Cancer\u003c/em\u003e. August 2024 [cited June 16, 2024];207:114156. Available at: https://linkinghub.elsevier.com/retrieve/pii/S0959804924008128\u003c/li\u003e\n\u003cli\u003eDowrick A, Ziebland S, Rai T, Friedemann Smith C, Nicholson BD. A manifesto for improving cancer detection: four key considerations when implementing innovations across the interface of primary and secondary care. \u003cem\u003eLancet Oncol\u003c/em\u003e. June 2024 [cited July 5, 2024];S1470204524001025. Available at: https://linkinghub.elsevier.com/retrieve/pii/S1470204524001025\u003c/li\u003e\n\u003cli\u003ePatel S, Goldsack JC, Cordovano G, Downing A, Fields KK, Geoghegan C, et al. Advancing Digital Health Innovation in Oncology: Priorities for High-Value Digital Transformation in Cancer Care. \u003cem\u003eJ Med Internet Res\u003c/em\u003e. January 4, 2023 [cited July 5, 2024];25:e43404. Available at: https://www.jmir.org/2023/1/e43404\u003c/li\u003e\n\u003cli\u003eMa F. The inauguration of \u003cem\u003eCancer Innovation\u003c/em\u003e: Leading New Frontiers in Oncology, Building Human Health Community. \u003cem\u003eCancer Innov\u003c/em\u003e. June 2022 [cited July 5, 2024];1(1):1\u0026ndash;2. Available at: https://onlinelibrary.wiley.com/doi/10.1002/cai2.19\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e: Respondents’ characteristics according to group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHealth\u0026nbsp;authority\u0026nbsp;group\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eN=26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOncology group\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eN=88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge, years, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e36.5 (32-42.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e51 (40.25-59.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFemale sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18 (69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37 (42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eProfession\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003ePhysicians\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eIncluding haematologists\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003ePharmacists\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (15%)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e0/3\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e15 (58%)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e7 (27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e69 (78%)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e15/86 (17%)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e7 (8%)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e12 (14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIQR, interquartile range\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"innovation, evidence, evaluation","lastPublishedDoi":"10.21203/rs.3.rs-6350857/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6350857/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e The word “innovation” is widely used in healthcare, especially in oncology. Innovation has been reported to impact the drug evaluation process, but there is no consensus regarding the evaluation of innovation. This study aimed to examine perceptions and attitudes (perceived benefits and concerns) towards innovation in clinical practice and in evaluation of innovation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and Methods\u003c/strong\u003e: We performed a cross-sectional, online, anonymous, voluntary survey among members of French associations of oncologists, haematologists, pharmacologists and therapists as well as members of the drug evaluation service of the French Health Technology Assessment body. The onlinequestionnaire assessed respondent characteristics as well as their level of agreement with several statements regarding the definition, extent, and evaluation of innovations (Supplementary materials). Most of the items were scored on an 11-point Likert scale. To provide a broader understanding of the respondent profiles, principal component analysis and cluster analysis were performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: A total of 114 participants completed the survey between April and June 2024, including 88 respondents in the oncology group and 26 respondents in the health authoritygroup. There were differences between groups in terms of age, sex, and profession. Three distinctive clusters of respondents were identified: one cluster of respondents looked for simplified evaluation of innovated drugs (all of whom in the oncology group), contrasted to one cluster stated that drug evaluation requires standard processes (almost 80% of whom were in the health authority group); and one cluster of respondents indifferent to the evaluation process (this group has equal distributions across the groups).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Innovation is perceived as being associated with the concepts of novelty, advance, and improvement. However, there were differences between groups regarding the level of evidence required to evaluate innovations. Efforts should be done to merge, rather than to oppose, and quantify all different types of evidence, for the patient interest.\u003c/p\u003e","manuscriptTitle":"Therapeutic innovation in oncology: What do you mean? What we cannot talk about, we must keep silent. L. 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