Top 10 research priorities in colorectal cancer: results from the Colorectal Cancer Priority-Setting Partnership

Among the malignant diseases, colorectal carcinoma (CRC) is the third-ranked cause of death in Germany and worldwide (Zentrum für Krebsregisterdaten and GEKID 2021). The number of German residents ≥ 65 years is projected to increase from 16.8 million in 2010 to 23.7 million (+ 41%) in 2040 (Pritzkuleit and Katalinic 2016). Due to this demographic trend, the incidence of CRC will also rise sharply (Statistisches Bundesamt 2009; Motel-Klingebiel et al. 2010; Suzman and Beard 2011; Robert-Koch Institut and Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V. 2015), probably growing from 79 to 120 per 100,000 inhabitants (Pritzkuleit and Katalinic 2016). CRC requires interdisciplinary and interprofessional care (cancer care continuum) (Feuerstein and Ganz 2011).

The topics of research projects are frequently determined by industry, e.g., pharmaceutical companies, or by public sponsors. Little is known about the perspectives of other relevant stakeholders, such as patients, family members, carers, nursing staff, treating physicians, or other health care professionals involved in care, because these groups generally do not become involved in the identification and prioritization of research topics. In many fields of medicine, this has led to discrepancies between the priorities of patients and the studies actually conducted (Crowe and Giles 2016).

Recent years have seen an increased awareness of the need to involve patients and the public in research (Jilani et al. 2020). Patient and public involvement should grant those concerned the opportunity to take an active part in the development of research programs and the design of research projects. An objective, transparent, and effective method of identifying and prioritizing evidence uncertainties is the concept of the “priority-setting partnership” (PSP, Forschungspartnerschaft) popularized by the James Lind Alliance (JLA, www.​jla.​nihr.​ac.​uk) (Partridge and Scadding 2004). The German PSP group (www.​forschungspartne​rschaft.​de) recently published, in cooperation with the JLA, the first German PSP on the treatment of pancreatic cancer (Klotz et al. 2020). The goal of the research project presented here is to work together with patients, carers, nursing staff, treating physicians, and other relevant stakeholders as equal partners to identify and prioritize open questions regarding the diagnosis, treatment, and follow-up of CRC. It is the first detailed description of a PSP in Germany and the first PSP for CRC worldwide.

The PSP was carried out in accordance with the published JLA guidelines (versions 9 and 10) (James Lind Alliance 2021). Every PSP consists of seven steps (Mihaljevic 2022).

In a transparent, validated process, the Colorectal Cancer PSP identified the 10 most important research priorities (Table 2) from the total of over 1100 unresolved questions submitted. These top 10 questions, and even more so the extended top 20 priorities (Supplement 5), show the wide diversity of still unanswered questions. Moreover, the priorities of patients and relatives diverged from those of healthcare professionals. The PSP process accorded equal weight to the opinions of the patients/carers and other stakeholders. This project is the first PSP for colorectal cancer, and to our knowledge, only one other PSP has been performed in German-speaking countries (Klotz et al. 2020).

Patient and public partnerships are a relatively new development in medical research but have attained great significance (Richards et al. 2013). This trend has been described as an “ethical imperative and essential to improving the quality, safety, value, and sustainability of health systems and research” (British Medical Journal 2021). In Germany, too, public funding bodies are demanding increased involvement of patients in medical research (BMBF 2021). The lack of participation by patients is viewed as responsible for the waste of resources in biomedical research (Chalmers et al. 2014). The UK National Institute for Health Research differentiates between involvement (public involvement in research as research being carried out ‘with’ or ‘by’ members of the public rather than ‘to’, ‘about’ or ‘for’ them), engagement (when information and knowledge about research is provided and disseminated to patients or the public), and participation (when people take part in a research study) (NIHR 2021). Within involvement, one has to distinguish among (a) consultation (when patients or the public are asked their opinion and the views expressed are incorporated into the decision-making process), (b) Collaboration (“involves an ongoing partnership between (researches) and the members of the public…, where decisions about the research are shared”), and (c) coproduction (when the research is a joint project of scientists, patients, and the public in which responsibility and decision-making are shared from beginning to end) (NIHR 2021). The PSP concept presented here features elements of all three areas (involvement, engagement, participation) and represents coproduction of knowledge. It thus differs from other forms of patient involvement (e.g., patient advisory boards), whose function is frequently limited to consultation.

Priority-setting partnerships have become a common, internationally accepted way of determining research priorities, but PSPs on oncological topics are relatively rare (James Lind Alliance 2021a, 2021b). Furthermore, contrary to other countries like the UK and Canada (James Lind Alliance 2021a, 2021b), PSPs (Forschungspartnerschaften) are still uncommon in Germany. To our knowledge only one previous PSP in Germany has been performed: for pancreatic cancer treatment by our group (Klotz et al. 2020). In terms of scope, number of participants, and number of topics proposed, the CRC PSP is comparable with some of the previous oncological PSPs (Nixon et al. 2020), while other oncological PSPs were much smaller (Lophatananon et al. 2011). The results of the CRC PSP show the need for research in many different areas and pertain to basic, translational, clinical, and health services research. Most of the topics prioritized will only be able to be resolved in the context of interdisciplinary and interprofessional research partnerships. The fact that several (pilot) trials are currently addressing topics raised by our PSP is an indication of the relevance of the results. An example is the research into total neoadjuvant treatment (TNT) in rectal cancer patients with the possibility of organ-preservation (e.g., NO-CUT trial NCT03565029).

The Colorectal Cancer PSP has several limitations. To begin with, the important subject of CRC screening and prevention was not included. This was decided by the steering group at an early stage to ensure that the size of the PSP remained manageable. Moreover, the anonymous nature of the survey precluded acquisition of more detailed data on the respondents. The participants could therefore be described only in general terms, and demographic data, such as social status and level of education, were not recorded. Whether any subgroups might not have been adequately represented cannot be stated with sufficient certainty. Therefore, no comparisons could be made between the respondents to the first and second surveys. Because the questionnaires were available only in German, selection bias cannot be ruled out. However, the large number of questions submitted, and the broad diversity of fields covered, together with the balanced participation of patients/carers and healthcare professionals, makes it likely that the results are representative. A further limitation is the focus on the German-speaking countries. Depending on the healthcare system, other countries may to some extent yield other findings. However, this limitation applies also to other PSPs (James Lind Alliance). Another limitation applying to all FP is the (lack of) balance between too specific and too general research questions. In the process of the FP (see “Methods” section) specific research questions, that are relevant to only a certain group of stakeholders, might be eliminated. On the other hand, by formulating indicative questions by consensus, some research questions might appear rather general. However, the process guarantees the selection of research questions relevant to all stakeholders. Furthermore, the objective of the FP is not to formulate a specific research question that can be answered by a single specific project, but rather to formulate research questions that need to be addressed by several studies, thereby reflecting the complexity of CRC care and research. Finally, during the process of the PSP, evidence uncertainties are checked against existing guidelines, current at that time. As the JLA standards for excluding questions based on evidence criteria are high (level 1 a/b according to the Oxford; see “Methods” section), some research questions might have been carried forward in the PSP, contrary to guideline recommendations that are based on lower than level 1 a/b evidence.

In summary, the Colorectal Cancer Priority-Setting Partnership has identified and ranked evidence uncertainties in the diagnosis, treatment, and follow-up of CRC important to patients, family members, carers, physicians, and other stakeholders alike. This PSP give researchers and research funders the opportunity to focus their efforts on topics prioritized by all relevant stakeholders. It is the first detailed description of a PSP in Germany, and the first PSP on CRC care worldwide.