M. Koller

Second Step: Testing—Outcome Measurements

Despite worldwide enthusiasm for endoscopic surgery, this new technology is now on the top of McKinlays “product life circle curve.” Critical questions are being asked about its benefits and burdens, but the concepts applied and the methodologies used for technology assessment are in a similar position as endoscopic surgery and need a critical evaluation. (1) There are incorrect and outdated concepts for the scientific basis of surgery (surgical theory) including the basic sciences involved; biomedicine still dominates, but assessment of outcome after operations is no longer possible without clinical epidemiology and social psychology. (2) Based on an outdated scientific theory for surgery, an outdated concept of disease is still propagated. It is denoted as mechanical and is based solely on biomedicine. Human subjects are reduced to biologic machines, and outcomes measurement excludes most dimensions of functioning and well-being. To achieve a valid result for outcome measures, a hermeneutic approach must be combined with the mechanical approach. (3) Based on an outdated model of disease, the outcomes used in endoscopic surgery rely too much on traditional measures, such as mortality rate, complication rate, hospital stay, and especially an endless list of biochemical mediators. Their alterations during the perioperative period have not yet been shown to be related to clinical or hermeneutic outcomes. A new method of assessment for clinical trials in endoscopic surgery and for other surgical problems is outlined, such as for surgical infections and for surgical oncology. It includes an index of recovery and objective health status assessed by the doctor, a quality-of-life self-report by the patient, and the true endpoint concept as a critical weighting of both types of outcome by patients and doctors.

Stufe-3-Leitlinie Brustkrebs-Früherkennung in Deutschland 2008

ZusammenfassungDie aktualisierte Stufe-3-Leitlinie Brustkrebs-Früherkennung in Deutschland 2008 vermittelt den wissenschaftlichen Kenntnisstand in evidenz- und konsensbasierter Form und ist unter Beteiligung der Deutschen Gesellschaft für Chirurgie e.V, der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen e.V. und 29 weiterer Fachgesellschaften, Berufsverbänden und nichtärztlichen Organisationen erstellt. Ziel der Stufe-3-Leitlinie ist es, Ärzte sowie gesunde und betroffene Frauen durch evidenzbasierte und formal konsentierte Empfehlungen bei anstehenden medizinischen Entscheidungen im Rahmen der Diagnosekette zur Früherkennung von Brustkrebs zu unterstützen. Die Leitlinie umfasst neben den Empfehlungen zur Diagnosekette die Beschreibung zur Ausgestaltung der Qualitätssicherung von Struktur-, Prozess- und Ergebnisqualität (Outcomes) sowie deren Evaluation durch einen Qualitätsindikatorensatz.Die aktualisierte Stufe-3-Leitlinie 2008 löst die 2003 erstellte Leitlinie ab.Die Leitlinienempfehlungen werden dargestellt. Die Details sind der Publikation in Geburtsh Frauenh 2008; 68: 251–26 zu entnehmen. Die Langfassung der Leitlinie ist als Buch im W. Zuckschwerdt Verlag GmbH/München erschienen und ist, wie der Methodenreport und der Evidenzreport auch, über die Internetseite www.awmf-leitlinien.de (Reg.: Nr. 077/001) frei zugänglich.AbstractThe updated 2008 German Guideline for Early Detection of Breast Cancer provides evidence-based and consensus-based recommendations of the knowledge gained by the German Society for Surgery and the German Society of Plastic, Aesthetic, and Reconstructive Surgeons together with 29 professional societies, associations, and nonmedical organizations. The guideline is meant to assist physicians, healthy women, and patients in medical decisions with recommendations regarding the diagnostic chain in early detection of breast cancer. In addition to these recommendations, the guideline also includes descriptions of quality assurance for resources, procedures, outcomes, and evaluation using a set of quality indicators. It updates the previous version from 2003. The guideline’s recommendations are presented. They are described in detail in the full publication (in German) Geburtsh Frauenh 2008; 68:251–261. The long version of the Guideline, methods report, and evidence report are available on the internet at www.awmf-leitlinien.de (reg. no. 077/001) with free access.The updated 2008 German Guideline for Early Detection of Breast Cancer provides evidence-based and consensus-based recommendations of the knowledge gained by the German Society for Surgery and the German Society of Plastic, Aesthetic, and Reconstructive Surgeons together with 29 professional societies, associations, and nonmedical organizations. The guideline is meant to assist physicians, healthy women, and patients in medical decisions with recommendations regarding the diagnostic chain in early detection of breast cancer. In addition to these recommendations, the guideline also includes descriptions of quality assurance for resources, procedures, outcomes, and evaluation using a set of quality indicators. It updates the previous version from 2003. The guidelines recommendations are presented. They are described in detail in the full publication (in German) Geburtsh Frauenh 2008; 68:251-261. The long version of the Guideline, methods report, and evidence report are available on the internet at www.awmf-leitlinien.de (reg. no. 077/001) with free access.

The use of differential item functioning analyses to identify cultural differences in responses to the EORTC QLQ-C30

IntroductionThe European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is a widely used health-related quality of life instrument. The main aim of this study is to investigate whether there are international differences in response to the questionnaire that can be explained by cultural factors.MethodsAnalyses involved a database of 106 separate studies including data from over 28,000 respondents. Differential item functioning (DIF) analyses using logistic regression were conducted for each item of the EORTC QLQ-C30 with respect to cultural/geographic group. Results were qualitatively compared with previously reported DIF analyses by translation to explore whether the source of the DIF was more likely to be linguistic or cultural in nature.ResultsAlthough most response patterns were similar, there were a number of international differences in how the questionnaire was answered. The largest variations were found in the results for Eastern Europe and East Asia. Results for the UK, the US and Australia tended to be similar. Many of the European results followed patterns that were more clearly explained when grouped by translation than when grouped by geographical region.DiscussionOur results suggest that, in general, the EORTC QLQ-C30 is suitable for use in a wide variety of countries and settings. Some response variations that have the potential to affect the results of international studies were identified, but it was not always clear whether the source of the variation was primarily linguistic or cultural.

Comparing translations of the EORTC QLQ-C30 using differential item functioning analyses

The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is one of the most widely used quality of life instruments for cancer patients. The aim of this study was to assess whether there were linguistic differences in the way an international sample answered the EORTC QLQ-C30 questionnaire. Thirteen translations of the EORTC QLQ-C30, representing 22 countries, were investigated using a database of 27,891 respondents, incorporating 103 separate studies. Differential item functioning (DIF) analyses were conducted using logistic regression to identify items which, after controlling for subscale, were answered differently by language of administration. Both uniform and non-uniform DIF were assessed. Although most languages showed similar results to English, at least one instance of statistically significant DIF was identified for each translation, and a few of these differences were large. In some cases, the patterns were supported by the results of qualitative interviews with bilingual people. Although, overall, there appeared to be good linguistic equivalence for most of the EORTC QLQ-C30 items, several scales showed strongly discrepant results for some translations. Some of these effects are large enough to impact on the results of clinical trials. Based on our experience in this study, we suggest that validation of translations of health-related quality of life instruments should include exploration of DIF.

Understanding quality of life in patients with colorectal cancer: comparison of data from a randomised controlled trial, a population based cohort study and the norm reference population

AbstractBackground and aims:Quality of life (QoL) is an important outcome measure in clinical studies. However, there is little experience with the interpretation of QoL results. Methods:To guide interpretation of QoL results from a randomised controlled trial (RCT) targeting the effectiveness of the immune modulator G-CSF on postoperative recovery in high risk (ASA III/IV) colorectal cancer patients, we compared RCT data with data from a population based cohort study and norm reference data. QoL was assessed using the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 and CR38 questionnaires. QoL results were analysed on discharge from hospital and six months postoperatively. Results:Colorectal cancer patients (both from the RCT and the cohort study) showed the greatest differences in QoL scores compared to norm reference data at discharge from hospital. Six months postoperatively, global quality of life and pain approximated norm reference values indicating optimal recovery. However, deficits still appeared in scores for role functioning, physical functioning, social functioning and fatigue. The best improvements (discharge from hospital to six months postoperatively) were seen with respect to physical functioning, fatigue and pain. Conclusions:For further analysis of RCT data, physical functioning and fatigue scores may be more sensitive than global quality of life to detect differences in treatment effects.

Outcome nach minimal-invasiver Chirurgie Qualitative Analyse und Bewertung der klinischen Relevanz von Studienendpunkten durch Patient und Arzt

Abstract.Introduction: Mechanistic study endpoints, evaluated exclusively by the physician, are mostly used in clinical studies evaluating new treatment modalities (e.g. laparoscopic cholecystectomy). Those endpoints often lack clinical relevance. The patients opinion concerning the importance of a study endpoint is particularly important in the evaluation of minimally invasive procedures, which place special emphasis on patient comfort. Methods: In a first step it was evaluated by meta-analysis, which clinical endpoints have been used for comparison of laparoscopic and conventional cholecystectomy. Furthermore, using a qualitative analysis it was investigated how important the individual study endpoints are for patients and physicians. Ten patients and five surgeons were questioned in a structured interview. Results: Of all outcome variables used world-wide, approximately one third were hermeneutic study endpoints, depending on the quality of the study, but often the method of evaluation was insufficient. Only three of 215 endpoints ( < 2 %) were quality of life scores, an integrated concept of outcome was missing completely. The qualitative analysis confirms the claimed difference between isolated and integrated evaluation of treatment goals. The importance of postoperative death is underestimated by patients and physicians; postoperative pain is overestimated. Patients ranked the outcome variable “restoration of full physical fitness“ as the most important study endpoint after avoidance of complications and death. It is underestimated in isolated evaluation and has not been used in the world literature at all. Conclusion: The analysis of clinical relevance of study endpoints should be the first and not the last step of studies to evaluate surgical technology. It cannot be based purely on intuition; it must make use of scientifically accepted techniques (e.g. qualitative analysis).Zusammenfassung.Einleitung: In klinischen Studien zur Evaluation neuer Behandlungsverfahren (wie z. B. bei der Einführung der laparoskopischen Cholecystektomie) werden zumeist mechanistische, allein vom Arzt evaluierte Studienendpunkte gewählt. Häufig fehlt solchen Endpunkten die klinische Relevanz. Gerade bei der Beurteilung von minimal-invasiven Behandlungsmethoden, bei denen der Patientenkomfort im Vordergrund steht, ist die Beurteilung eines Studienendpunkts durch Patienten besonders wichtig. Methoden: Es wurde zunächst im Rahmen einer Metaanalyse evaluiert, welche klinischen Studienendpunkte beim Vergleich von laparoskopischer und konventioneller Cholecystektomie bisher verwendet wurden. Anschließend wurde mit einer qualitativen Analyse untersucht, welche Bedeutung den einzelnen Studienendpunkten von Patienten und Ärzten beigemessen wird. Hierzu wurden 10 Patienten und 5 Chirurgen in einem strukturierten Interview befragt. Ergebnisse: In Abhängigkeit von der Studienqualität wurden weltweit zu etwa einem Drittel hermeneutische Gesundheitsziele (Endpunkte) eingesetzt, aber vielfach mit ungenügender Methode. Lebensqualitätsscores wurden als 3 von 215 Endpunkten verwendet ( < 2 %), ein integratives Konzept von Outcome fehlte vollständig. Die qualitative Analyse weist den behaupteten Unterschied zwischen isolierter und integrativer Bewertung von Gesundheitszielen nach. Der postoperative Tod wurde von Patient und Arzt unterschätzt, der postoperative Schmerz überschätzt. Das von Patienten nach Vermeidung von Komplikationen und Tod am höchsten bewertete Gesundheitsziel „Wiederherstellung der vollen physischen Belastbarkeit“ wurde bei isolierter Wertung unterschätzt und tauchte in Studien der Weltliteratur überhaupt nicht auf. Schlussfolgerung: Eine Werteanalyse der klinischen Relevanz von Studienendpunkten muss an den Beginn, nicht ans Ende von Studien zur chirurgischen Technologiebewertung gestellt werden. Diese darf nicht allein aus Intuition kommen, sie muss sich heute wissenschaftlich anerkannter Methoden (z. B. qualitativer Analyse) bedienen.

2008 update of the guideline: early detection of breast cancer in Germany

IntroductionThe goal of the 2008 updated guideline: early detection of breast cancer in Germany is to support physicians as well as healthy and affected women in the decision-making process involved in the diagnostic chain for the early detection of breast cancer by providing them with evidence- and consensus-based recommendations. The updated guideline replaces the guideline issued in 2003.Materials and methodsThe guideline forms the basis for developing an effective and efficient national early breast cancer detection program that meets the standards set by the Council of Europe and WHO for cancer control programs. The guideline presents the current, evidence- and consensus-based state of scientific knowledge in a multidisciplinary approach for the entire diagnostic chain, consisting of history taking and risk consultation, information on health behavior, clinical breast examination, diagnostic imaging, image-guided percutaneous tissue-acquisition techniques, open surgical excisional biopsy and pathomorphological tissue evaluation. The guideline recommends a set of quality indicators to assure resource availability, performance quality and outcomes enhancing total quality management for early breast cancer diagnosis.Conclusion Currently, early detection of breast cancer offers the most promising possibility to optimize the diagnosis and treatment of breast cancer and, as a result, reduce breast cancer mortality and improve health related quality of life in women.

Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4)¶ Protocol of a controlled clinical trial developed by consensus of an international study group¶ Part one: rationale and hypothesis

Abstract:General design: Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). This part describes the design of the randomised, placebo controlled, double-blinded, single-centre study performed at an university hospital (n = 40 patients for each group).¶Objective: The trial design includes the following elements for a prototype protocol:¶ - The study population is restricted to patients with colorectal cancer, including a left sided resection and an increased perioperative risk (ASA 3 and 4).¶ - Patients are allocated by random to the control or treatment group.¶ - The double blinding strategy of the trial is assessed by psychometric indices.¶ - An endpoint construct with quality of life (EORTC QLQ-C30) and a recovery index (modified Mc Peek index) are used as primary endpoints. Qualitative analysis of clinical relevance of the endpoints is performed by both patients and doctors.¶ - Statistical analysis uses an area under the curve (AUC) model for improvement of quality of life on leaving hospital and two and six months after operation. A confirmatory statistical model with quality of life as the first primary endpoint in the hierarchic test procedure is used. Expectations of patients and surgeons and the negative affect are analysed by social psychological scales.¶Conclusion: This study design differs from other trials on preoperative prophylaxis and postoperative recovery, and has been developed to try a new concept and avoid previous failures.¶

Differential item functioning (DIF) in the EORTC QLQ-C30: a comparison of baseline, on-treatment and off-treatment data.

AbstractIntroduction Differential item functioning (DIF) analyses can be used to explore translation, cultural, gender or other differences in the performance of quality of life (QoL) instruments. These analyses are commonly performed using “baseline” or pretreatment data. We previously reported DIF analyses to examine the pattern of item responses for translations of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 QoL instrument, using only data collected prior to cancer treatment. We now compare the consistency of these results with similar analyses of on-treatment and off-treatment assessments and explore whether item relationships differ from those at baseline. Methods Logistic regression DIF analyses were used to examine the translation of each item in each multi-item scale at the three time points, after controlling for the overall scale score and other covariates. The consistency of results at the three time points was explored. Results For most EORTC QLQ-C30 subscales, the DIF results were very consistent across the three time points. Results for the Nausea and Vomiting scale varied the most across assessments. Discussion The results indicated that DIF analyses were stable across each time point and that the same DIF effects were usually found regardless of the treatment status of the respondent.

Survival chances and psychological aspects of quality of life in patients with localized early stage breast cancer

AbstractBackground:The present analysis focuses on the long term psychological reactions to early stage breast cancer. Two hypotheses were formulated. The first hypothesis draws a direct link between tumour size/survival chances and Quality of life (QoL): The better the survival chances, the better QoL (‘biological danger model’). The second hypothesis assumes that localized early breast cancer has excellent prognosis (>90% five year survival rate), and that therefore QoL differences between various forms of early breast cancer should be minimal (‘medico-pragmatic model’). Patients and methods:In a defined rural area with 252.000 inhabitants (small-area-analysis), a total of n = 389 patients with primary breast cancer were recruited. For the present analysis we selected a subgroup (n = 269) from the cohort by tumour size (pTis, pT1a,b, pT1c, and pT2). QoL scores for global quality of life, emotional functioning and future perspective were computed according to the EORTC manual and compared to age-matched norm data of the German population. Results:A total of 690 QoL questionnaires were obtained from n = 269 patients with comparable completion rates within the four subgroups (pTis, pT1a,b, pT1c, and pT2).For all four groups and in all scores there were improvements over time. Generally, pTis always scored highest, pT2 always lowest, the other two groups in between.After one year pTis patients had higher mean scores in global quality of life than the norm. In contrast, pT1a,b were considerably lower than the norm and the difference between these two was 17.2 score points. It seems that the small difference (3.5%) in five year survival chances between pTis and T1 a,b tumours transforms into marked differences regarding quality of life, thus supporting a biological danger model of the survival/QoL relationship. Conclusions:Our results show that physicians have to realise although their early breast cancer patients have excellent survival chances, psychological distress is present. From a clinical perspective we would recommend that early stage breast cancer patients, and especially patients with occult, pT1a,b tumours be informed about their excellent prognosis. In addition, cognitive therapy might help patients stop worrying about their cancer.