Use, applicability, and dissemination of patient versions of clinical practice guidelines in oncology in Germany: a qualitative interview study with healthcare providers.

BACKGROUND: People with cancer have high information needs; however, they are often inadequately met. Patient versions of clinical practice guidelines (PVGs), a special form of evidence-based information, translate patient-relevant recommendations from clinical practice guidelines into lay language. To date, little is known about the experience of PVGs from healthcare providers' perspective in healthcare. This study aims to investigate the use, applicability, and dissemination of PVGs in oncology from the healthcare providers' perspective in Germany. METHODS: Twenty semi-structured telephone interviews were conducted with oncological healthcare providers in Germany between October and December 2021. Interviews were recorded and transcribed verbatim. Mayring's qualitative content analysis with MAXQDA software was utilised to analyse the data. RESULTS: A total of 20 healthcare providers (14 female, 6 male), mainly working as psychotherapists/psycho-oncologists and physicians, participated. Most participants (75%) were aware of the existence of PVGs. The content was predominantly perceived as comprehensible and relevant, whereas opinions on the design and format were mixed. The perceived lack of up-to-date information limited participants' trust in the content. Most felt that PVGs positively impact healthcare owing to the fact that they improve patients' knowledge about their disease. Additionally, PVGs served as a guide and helped healthcare providers structure physician-patient talks. Healthcare provider's unawareness of the existence of PVGs was cited as an obstructive factor to its dissemination to patients. CONCLUSION: Limited knowledge of the existence of PVGs among healthcare providers, coupled with alternative patient information, hinders the use and dissemination of PVGs in healthcare. However, the applicability of PVGs seemed to be acceptable owing to their content and good comprehensibility, especially with respect to physician-patient communication.

Barriers and facilitators in developing patient versions of clinical practice guidelines - qualitative interviews on experiences of international guideline producers.

BACKGROUND: Several guideline organizations produce patient versions of clinical practice guidelines (PVGs) which translate recommendations into simple language. A former study of our working group revealed that few guideline organizations publish their methods used to develop PVGs. Clear definitions of PVGs do not prevail and their purposes often remain unclear. We aimed to explore experts' perspectives on developing, disseminating and implementing PVGs to discuss and incorporate these experiences when consenting on methodological guidance and further improving PVGs. METHODS: We conducted 17 semi-structured telephone interviews with international experts working with PVGs from September 2021 through January 2022. We conducted the interviews in English or German, they were recorded and transcribed verbatim. We utilized Mayring's qualitative content analysis with MAXQDA software to analyze the data. RESULTS: In two interviews two participants were interviewed at the same time. This resulted in a total of 19 participants from 16 different organizations and eight different countries participated. Most were female (16/19) and their experience in working with PVGs ranged from 1 to 20 years. All follow methodological standards when developing PVGs, but the extent of these standards and their public accessibility differs. Aims and target groups of PVGs vary between organizations. Facilitators for developing PVGs are working with a multidisciplinary team, financial resources, consultation processes and a high-quality underlying CPG. Facilitators for disseminating and implementing PVGs are using various strategies. Barriers, on the other hand, are the lack of these factors. All participants mentioned patient involvement as a key aspect in PVG development. CONCLUSION: The steps in the PVG development process are largely similar across the countries. Focus is placed on the involvement of patients in the development process, although the extent of participation varies. The experts collectively attribute great importance to PVGs overall, but in order to constantly adapt to medical progress and changing conditions, the focus in the future may be more on formats like living guidelines. Although there are different views on the mandatory development of PVGs, there is a consistent call for more transparency regarding the methodology used for PVGs.

S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Design and Preclinical Characterization Program toward Asundexian (BAY 2433334), an Oral Factor XIa Inhibitor for the Prevention and Treatment of Thromboembolic Disorders.

Activated coagulation factor XI (FXIa) is a highly attractive antithrombotic target as it contributes to the development and progression of thrombosis but is thought to play only a minor role in hemostasis so that its inhibition may allow for decoupling of antithrombotic efficacy and bleeding time prolongation. Herein, we report our major efforts to identify an orally bioavailable, reversible FXIa inhibitor. Using a protein structure-based de novo design approach, we identified a novel micromolar hit with attractive physicochemical properties. During lead modification, a critical problem was balancing potency and absorption by focusing on the most important interactions of the lead series with FXIa while simultaneously seeking to improve metabolic stability and the cytochrome P450 interaction profile. In clinical trials, the resulting compound from our extensive research program, asundexian (BAY 2433334), proved to possess the desired DMPK properties for once-daily oral dosing, and even more importantly, the initial pharmacological hypothesis was confirmed.

Heterogeneous methodology in the development of patient versions of clinical practice guidelines: a scoping review.

OBJECTIVES: We aimed to gain an overview of the methods and approaches used to develop, disseminate, and implement patient versions of clinical practice guidelines (PVGs). METHODS: We searched PubMed and MEDLINE through Ovid for articles reporting on the development, dissemination, or implementation of PVGs until March 2022. We searched the homepages of guideline organizations, screened the reference lists of the included documents, and asked experts to complement the publications. We narratively synthesized the findings. RESULTS: Of 3,941 publications screened, 27 were included in the study. The identified method reports focused on patient involvement and peer-review processes. The other included publications highlighted the relevance of broad dissemination strategies and emphasized the importance of patient involvement and improving the readability of PVGs by using lay terms and shorter sentences. CONCLUSION: The terminology used for PVGs varies widely. The extent to which the methods were described was heterogeneous. Organizations developing PVGs should make their methods publicly available and use uniform labeling for PVGs in English to improve their use and recognition, not only for other PVG producers but also for patients and the public. A consensus regarding a minimum reporting standard for developing PVGs internationally and developing guiding principles is desirable.

Implementation and update of guideline-derived quality indicators for cervical cancer in gynecological cancer centers certified by the German Cancer Society (DKG).

PURPOSE: In 2008, the first gynecological cancer centres were certified by the German Cancer Society (DKG). Guideline-based quality Indicators (QIs) are a core element of the certification process. These QI are defined to assess the quality of care within the centres and can serve to measure the implementation of guideline recommendation. This article aims to give an overview of the developing and updating process of guideline based-QIs for women with cervical cancer and presents the QI results from the certified gynaecological cancer centres. METHODS: The QIs are derived in a multiple step review process and then implemented in the certification data sheet of the certified centres. The first set of QIs created in 2014 was revised in the update process of the S3-Guideline in 2020. QIs are based on strong recommendations of the evidence-based "Guideline for patients with Cervical Carcinoma" (registry-number: 032/033OL). RESULTS: In total, there are nine guideline-based QIs for cervical cancer. Four QIs are part of the certification process. In the treatment year 2020, 3.522 cases of cervical cancer were treated in 169 centers. The target values for the four QIs were met in at least 95% of the certified centers. In the guideline update in 2020, a new QI was added to the set of QIs "Complete pathological report on conization findings" and the QI "Exenteration" was removed. CONCLUSIONS: QIs derived from strong recommendations of a guideline are an important tool to make essential parts of patient's care measurable and enable the centers to draw consequences in process optimization. Over the years, the number of certified centers has grown, and the quality was improved. The certification systems is under constant revision to further improve patient's care in the future, based on the results of the QI re-evaluation.

Identification and characterization of the new generation soluble guanylate cyclase stimulator BAY-747 designed for the treatment of resistant hypertension.

BACKGROUND AND PURPOSE: First-generation soluble guanylate cyclase (sGC) stimulators have shown clinical benefit in pulmonary hypertension (riociguat) and chronic heart failure (vericiguat). However, given the broad therapeutic opportunities for sGC stimulators, tailored molecules for distinct indications are required. EXPERIMENTAL APPROACH: We report the high-throughput screening (HTS)-based discovery of a second generation of sGC stimulators from a novel imidazo[1,2-a]pyridine lead series. An intense medicinal chemistry programme resulted in the discovery of the sGC stimulator BAY 1165747 (BAY-747). The pharmacokinetic profile of BAY-747 was determined in different species, and it was broadly characterized in pharmacological model systems relevant for vasodilatation and hypertension. KEY RESULTS: BAY-747 is a highly potent sGC stimulator in vitro. In addition, BAY-747 showed an excellent pharmacokinetic profile with long half-life and low peak-to-trough ratio. BAY-747 was investigated in experimental in vivo models of malignant and resistant hypertension (rHT). In spontaneously hypertensive (SH) rats, BAY-747 caused a dose-related and long-lasting decrease in mean arterial blood pressure (MAP). Oral treatment over 12 days resulted in a persistent decrease. BAY-747 provided additional benefit when dosed on top of losartan, amlodipine or spironolactone and even on top of triple combinations of frequently used antihypertensive drugs. In a new canine model of rHT, BAY-747 caused a dose-related and long-lasting (>6 h) MAP decrease. CONCLUSION AND IMPLICATIONS: BAY-747 is a potent, orally available sGC stimulator. BAY-747 shows long-acting pharmacodynamic effects with a very low peak-to-trough ratio. BAY-747 could be a treatment alternative for patients with hypertension, especially those not responding to standard-of-care therapy.

New Generation of sGC Stimulators: Discovery of Imidazo[1,2-a]pyridine Carboxamide BAY 1165747 (BAY-747), a Long-Acting Soluble Guanylate Cyclase Stimulator for the Treatment of Resistant Hypertension.

Herein, we describe the identification, chemical optimization, and preclinical characterization of novel soluble guanylate cyclase (sGC) stimulators. Given the very broad therapeutic opportunities for sGC stimulators, new tailored molecules for distinct indications with specific pharmacokinetics, tissue distribution, and physicochemical properties will be required in the future. Here, we report the ultrahigh-throughput (uHTS)-based discovery of a new class of sGC stimulators from an imidazo[1,2-a]pyridine lead series. Through the extensive and staggered optimization of the initial screening hit, liabilities such as potency, metabolic stability, permeation, and solubility could be substantially improved in parallel. These efforts resulted ultimately in the discovery of the new sGC stimulators 22 and 28. It turned out that BAY 1165747 (BAY-747, 28) could be an ideal treatment alternative for patients with hypertension, especially those not responding to standard anti-hypertensive therapy (resistant hypertension). BAY-747 (28) demonstrated sustained hemodynamic effects up to 24 h in phase 1 studies.

The effectiveness of clinical guideline implementation strategies in oncology-a systematic review.

IMPORTANCE: Guideline recommendations do not necessarily translate into changes in clinical practice behaviour or better patient outcomes. OBJECTIVE: This systematic review aims to identify recent clinical guideline implementation strategies in oncology and to determine their effect primarily on patient-relevant outcomes and secondarily on healthcare professionals' adherence. METHODS: A systematic search of five electronic databases (PubMed, Web of Science, GIN, CENTRAL, CINAHL) was conducted on 16 december 2022. Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) assessing the effectiveness of guideline implementation strategies on patient-relevant outcomes (overall survival, quality of life, adverse events) and healthcare professionals' adherence outcomes (screening, referral, prescribing, attitudes, knowledge) in the oncological setting were targeted. The Cochrane risk-of-bias tool and the ROBINS-I tool were used for assessing the risk of bias. Certainty in the evidence was evaluated according to GRADE recommendations. This review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42021268593. FINDINGS: Of 1326 records identified, nine studies, five cluster RCTs and four controlled before-and after studies, were included in the narrative synthesis. All nine studies assess the effect of multi-component interventions in 3577 cancer patients and more than 450 oncologists, nurses and medical staff. PATIENT-LEVEL: Educational meetings combined with materials, opinion leaders, audit and feedback, a tailored intervention or academic detailing may have little to no effect on overall survival, quality of life and adverse events of cancer patients compared to no intervention, however, the evidence is either uncertain or very uncertain. PROVIDER-LEVEL: Multi-component interventions may increase or slightly increase guideline adherence regarding screening, referral and prescribing behaviour of healthcare professionals according to guidelines, but the certainty in evidence is low. The interventions may have little to no effect on attitudes and knowledge of healthcare professionals, still, the evidence is very uncertain. CONCLUSIONS AND RELEVANCE: Knowledge and skill accumulation through team-oriented or online educational training and dissemination of materials embedded in multi-component interventions seem to be the most frequently researched guideline implementation strategies in oncology recently. This systematic review provides an overview of recent guideline implementation strategies in oncology, encourages future implementation research in this area and informs policymakers and professional organisations on the development and adoption of implementation strategies.

[S3 guideline on skin cancer prevention: evaluation and updating procedure]. / S3-Leitlinie Prävention von Hautkrebs: Evaluation und Aktualisierungsprozess.

BACKGROUND: Originally published in 2014, the S3 guideline "Prevention of skin cancer" is the first evidence-based guideline available exclusively for primary and secondary prevention, which summarizes interprofessional consented recommendations for skin cancer risk reduction and early detection. Due to the large number of new publications and expanding focus, an update was deemed necessary. METHODS: After a structured needs assessment, key questions were prioritized. The resulting systematic literature search resulted in a three-stage screening process. Recommendations formulated in working groups were approved in a formal consensus process, taking into account conflicts of interest, and finalized after a 6­week public consultation process. RESULTS: The needs assessment identified "skin cancer screening" (60.1%), "individual risk avoidance behaviors" (44.20%), and "risk factors" (43.48%) as topics of greatest interest. The prioritization phase resulted in 41 new key questions. A total of 22 key issues were re-evaluated in an evidence-based manner using 93 publications. As part of comprehensive guideline restructuring, 61 recommendations were newly developed and 43 were modified. The consultation phase resulted in no changes to recommendations and 33 changes to background material. CONCLUSION: The identified need for change resulted in extensive modification and redrafting of recommendations. As the target group "nononcology patients" cannot be identified via cancer registries or certification systems, no quality indicators can be derived from the guideline. To transfer the guideline to health care, innovative, addressee-specific concepts are required, which will be discussed and implemented during the preparation of the patient guideline.