Introduction
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.forschungspartnerschaft.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.
Methods
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).
The project began with the formation of a steering group to supervise the entire process. The steering group was supported by an adviser from the JLA (TG). The members of the steering group defined the aims and scope of the CRC PSP (Supplement 1):
(1)
Transparent and systematic identification of unresolved research questions regarding the diagnosis, treatment, and follow-up of patients with CRC, taking account of the interests of all relevant stakeholders.
(2)
Joint prioritization of the research topics identified, taking account of the interests of all relevant stakeholders.
(3)
Publication und dissemination of the results.
CRC screening was explicitly excluded so as to restrict the PSP to manageable dimensions. The steering group met to discuss the progress of the PSP at regular intervals. All steps of the PSP were debated and agreed in the steering group. A core team (RK, CDH, MH, AM) implemented the steering group’s decisions. The steering group contacted a large number of self-help groups and professional societies to request their cooperation in the project, particularly with regard to the distribution of the two surveys.
Step 2: First survey to identify unresolved research topics
The questions were formulated according to the recommendations of the JLA and included examples and prompts (Supplement 2). The questionnaire was distributed on paper as well as being made available on the homepages of the PSP and the partners in the project. It was also sent to CRC centers certified by the German Cancer Society (Darmkrebszentren) and to relevant professional associations. Moreover, patients and healthcare professionals were approached directly. The online questionnaire was implemented using the survey tool LimeSurvey. Given the anonymous nature of the questionnaire, the ethics committee of the University of Heidelberg determined that no legal consultation was required. The first questionnaire was available from 1 July 2020 to 31 October 2020.
Step 3: Classification and formulation of the research questions
The members of the core team (RK, MH, CDH, AM) collected and processed all of the research questions proposed by the respondents to the first survey. Topics considered to be beyond the scope of the Colorectal Cancer PSP were referred to the steering group, where they were discussed and, if agreement was reached, excluded. Moreover, the individual topics were categorized according to content.
Step 4: Review of available evidence and exclusion of questions already resolved
The members of the core team scrutinized CRC guidelines (as of October 2020) to identify further unresolved research questions and determine which of the questions raised by the survey respondents had already been answered (see list of guidelines in Supplement 7). The core team and steering group then refined the content and formulation of all remaining items so as to arrive at indicative questions in the PICO format (patient, intervention, comparison, outcome). In the course of this process, similar questions raised by several participants were amalgamated into one single question. Furthermore, questions that had already been resolved were eliminated from the pool of topics if the steering group was aware of the existence of evidence classified as level 1 a/b according to the Oxford Level of Evidence table (Oxford Centre for Evidence-Based Medicine
2009). The resulting catalog of indicative questions was compared with the available evidence as determined by means of a literature search. To this end, the Cochrane Database was searched by an information specialist and by the PSP core team. Again, a research topic was considered resolved if level1 a/b evidence was found (Oxford Centre for Evidence-Based Medicine
2009).
Step 5: Second survey for the purpose of interim ranking
The catalog of indicative questions generated in step 4 served as the basis for the second survey. The questionnaire could be completed online or on paper at any time from 1 May 2021 to 31 July 2021. The participants were asked to select from the catalog the 10 research priorities they considered most important (top 10) (Supplement 3). In the digital version of the questionnaire, the topics were presented in a new random order each time the form was opened. As in the first survey, the respondents were asked to specify their sex, age group, and whether they were patients/carers or healthcare professionals.
Step 6: Consensus workshop for final ranking
The final consensus workshop took place in Heidelberg on 11 September 2021. The JLA consultant (TG) ensured that the process adhered to the JLA guidelines (James Lind Alliance
2021). The workshop participants were patients/carers and healthcare professionals in equal numbers. The majority of the participants had not been involved in the PSP process prior to the workshop, but some were members of the steering group. Three specifically trained advisors (AA, CDH, RK) served as independent facilitators in the group discussions and ensured that the discussions were balanced. The research priorities were ranked according to the nominal group technique (James Lind Alliance
2021). The results of the interim prioritization were discussed and re-ranked in two rounds of discussion, in each of which three balanced small groups met in parallel. Based on the results of the second round of discussion, a concluding plenary session of all participants reached a consensus on the final top 10 list.
Step 7: Publication and dissemination of results
After publication of the paper, results will be made available to patient organizations, funding bodies and researchers.
Discussion
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.
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