The current study has the following two objectives:
To discern the most cost minimizing surgical peri-operative treatment program for colon cancer patients and to indicate justification or rejection of investments in these hospitals.
To supplement the lack of knowledge in literature on cost minimizing differences between the three treatment programs and to provide recommendations on further development in the operative treatment of colon carcinomas from an economic point of view.
The Tapas-study is a multicenter prospective cohort study. Randomised Controlled Trials are considered to give the highest level of evidence. Since randomization produces the best comparable groups, which is methodological the best manner to compare the intervention group with the conventional/standard group. However, cohort studies can easily separate complex multidisciplinary treatment programs such as ERAS into time and place, preventing an important bias: the attrition bias. An attrition bias occurs when elements of the control and alternative intervention mix and hence influences outcome. This explains why studies with ERAS are often correctly designed as cohort studies and not as randomized controlled trials [21, 22].
Conventional open surgery is the control exposure (cohort 1). Open surgery with ERAS recovery (cohort 2) and laparoscopic surgery with ERAS recovery (cohort 3) are the alternative exposures. Three separate consecutive time periods are used in order to prevent attrition bias. Before each new cohort starts a quality control assessment will be carried out by the expert project advisors from the research group on ERAS recovery and laparoscopic surgery.
Primary and secondary endpoints
The primary endpoint of the Tapas-study are costs, both direct medical en indirect non medical costs. Direct medical costs are defined as the total costs of medical resources used for diagnostics, therapy, revalidation and peri-operative care. Indirect non medical costs are defined as the total costs due to loss of productivity measured by the time back to work.
Secondary endpoints are total postoperative hospital stay in days, including hospital stay ofpatients who are readmitted within 30 days after surgery and quality of life and health status after 6 weeks, 3 months and one year after surgery. Quality of life and health status will be measured by two validated questionnaires; Short Form 36 (SF-36) and the WHOQOL-100. Further secondary endpoints are complications and mortality within 30 days after surgery, readmission rates, time back to work and differences in surgical-oncological radicality between open and laparoscopic surgery.
Five Dutch hospitals including one university medical centre en four general teaching hospitals, comparable by size and expertise, will enroll patients.
The study population consists of all patients with colon carcinoma, eligible for surgical treatment within the study period January 2007 to July 2010.
Inclusion criteria are: patients with a primary colon carcinoma, over 18 years of age, ASA I en II, who give informed consent.
Exclusion criteria are: pregnancy, ASA III-IV, previous abdominal surgery and metastasized illness.
This study is conducted in accordance with the principles of the Declaration of Helsinki and 'good clinical practice' guidelines. All collected data will be kept confidential at all times. The independent medical ethics committees of all participating hospitals have approved the study protocol. Prior to inclusion, written informed consent will be obtained from all patients.
The proposed cohort study carries no additional risks, as extra diagnostics or other than established treatment methods will not be used.
Inclusion and informed consent is obtained at the outpatient clinic. The patient is presented the appropriate treatment modality according to the current cohort, after which informed consent for that specific treatment is obtained.
Patients assigned to cohort 2 and 3 with ERAS recovery will receive additional information about the ERAS program by an ERAS nurse and an anesthesiologist prior to hospital admittance. All patients in cohort 2 and 3 will be admitted to a ward, were nurses and medical staff are trained in the ERAS program, and the ERAS protocol used is checked by the project experts.
Patients included into the third cohort will be operated by an experienced laparoscopic surgeon. The requirement for surgeons to perform laparoscopic colon surgery is 20 completed procedures.
To accomplish standardization and quality of care of the participating hospitals, prior to the start of the study every clinic is visited and agreements will be made on peri-operative care and the surgical procedures. For cohort 1 a protocol which defines traditional/conventional care will be uses by every hospital. Before cohort 2, an ERAS-expert panel visits the hospitals to check and agree upon the ERAS elements used in the clinic. A minimum number of 8 ERAS elements or more will be considered as ERAS peri-operative care. Before cohort 3, a quality control assessment will be performed in every hospital by experts on laparoscopic colon surgery, also accomplishing standardization of the laparoscopic methods used.
Whether the discharge criteria are met will be assessed and scored on every postoperative day. Discharge criteria include adequate pain control with oral analgesics, no nausea and ability to take solid foods, intestinal passage of flatus and/or stool, mobilization and self support as comparable to the preoperative level, agreement of the patient.
Intention to Treat
The analysis will be performed in accordance with the intention to treat principle.
Sample size calculation
We used an extensive table to calculate all direct medical costs including overhead and consultant costs for open and laparoscopic colon surgery for an average Dutch hospital. The main cost differences were due to the difference in operating time, use of (disposable) laparoscopic instruments and hospital stay. Based on our costs calculation, for each patient the difference in direct medical costs between laparoscopic colectomy en open colectomy is 2967 euro (38%). Considering approximately 9000 colon carcinoma operations performed annually in the Netherlands http://www.prismant.nl, the hypothetical direct costs of all 'open' colectomies performed are 38.7 million euro. The hypothetical direct costs of laparoscopically colectomies for the Netherlands are 65.3 million euro. Performing all colectomies in the Netherlands by a laparoscopic technique would result in 26.7 (= 38%) euro extra direct costs compared to performing all colectomies by the open technique.
Power calculation of the study
p1 (direct medical cost of laparoscopic colon surgery in the Netherlands) = 100 %
p2 (direct medical cost of open colon surgery in the Netherlands) = 62%
alfa = 0.01, beta = 0.05, f = 17.8
Based on differences of approximately 2000 euro found in literature form other countries, the number needed in each group would be n = 43. Therefore a more conservative trial size of 3 × 40 = 120 patients is taken into account.
In the cost minimization study direct medical costs and the indirect non medical costs are estimated. For the direct medical costs the method of real cost price calculation will be used. This will include the additional costs of laparoscopy, of ERAS care, as well as the differences due to complications and readmission. For indirect non medical costs the friction cost method will be used . This also allows us to limit the study period to one year post operatively. On the direct non medical costs and indirect medical costs assumptions of equality are made and these costs are not accounted for in this study.
Data collection and monitoring
Data are collected in a specially designed case-record form, both in the outpatient clinic as during hospital stay. Preoperatively, as well as 6 weeks, 12 weeks and one year postoperatively quality of life questionnaires (SF-36/GIQLI, Vaizey) are filled in by the patient.
The overall study period is 30 months: three cohort periods followed by one year of data analysis and synthesis. Because of the end points used (i.e. direct medical costs and indirect medical costs due to rehabilitation to normal work/activity), a longer follow up is not indicated. At one year all important differences in recovery and rehabilitation to normal life and work can be analyzed. Middle and long term outcomes measures (like oncological recurrences and late secondary complications like adhesions and incisional hernias) will not be included. Histopathological result of resections will be evaluated and compared.
There will be regular contact between the study coordinators and the participating centers, and all included data will be monitored by a research fellow.