Biomedical subjects

J Högel

Publications and source records attributed to J Högel.

At least 19 recordsLinked to original sources

PubMed2003

Guidelines for the intramuscular positioning of EMG electrodes in the semispinalis capitis and cervicis muscles.

The objective of the study was to establish guidelines for the application of fine-wire or needle electrodes in the semispinalis cervicis and semispinalis capitis muscles. First of all, measured data for the puncture angle and puncture depth of each muscle were determined in CT scans. Using a regression approach, a model relation of these data with the neck circumference was established. This made it possible to accurately determine the puncture angle and puncture depth on the basis of the known neck circumference. In a further step, the neck muscles of seven human cadavers were punctured with wires in order to check the workability of these guidelines. At the same time, the wires' positions in relation to important structures (nerves, vessels) were studied. Both muscles can be punctured with a high degree of reliability. However, when puncturing the semispinalis cervicis muscle, one has to pass through a layer that contains vessels, nevertheless the risk of injury is regarded as very small. The technique enables intramuscular EMG measurements of the two muscles in manifold clinical problems.

Electrodes↗

PubMed2001

Hydrolysed protein accelerates the gastrointestinal transport of formula in preterm infants.

UNLABELLED: Vomiting, large gastric residuals and abdominal distension are common in very immature infants on formula feeding. The present trial investigated whether a protein hydrolysate formula reduces the gastrointestinal transit time in preterm infants. Fifteen preterm infants (median gestational age 29 (24-32) wk, birthweight 1241 (660-1900) g, postnatal age 18 (5-54) d) on full enteral feeds (>150 ml/kg*d) were enrolled. It was hypothesized that the gastrointestinal transit time is at least 2 h shorter when protein hydrolysate formula is fed compared with standard preterm formula. In a randomized cross-over design study, each formula was fed for 5 d. On days 4 and 9 the gastrointestinal transit time was estimated using carmine red. The protein hydrolysate formula had a markedly shorter gastrointestinal transit time (9.8 h) than the standard formula (19 h) (p = 0.0022, two-sided Mann-Whitney U test). CONCLUSION: The hydrolysate protein formula accelerated gastrointestinal transit of milk and stools, but whether hydrolysate formulas enable a more rapid establishment of full enteral feeding in preterm infants needs to be investigated.

Carmine↗

PubMed2000

Evaluation of three risk scores to predict postoperative nausea and vomiting.

BACKGROUND: So far there are three different scores to predict postoperative vomiting (PV: Apfel et al., 1998) or postoperative nausea and vomiting (PONV: Koivuranta et al., 1997; Palazzo and Evans, 1993). All three scores used logistic regression analysis to identify and create weights for the risk factors for PV or PONV. In short, these were sex, age, history of previous PONV, motion sickness, duration of anaesthesia, and use of postoperative opioids. However, an external evaluation and a comparison of these scores has not been performed so far. METHODS: Patients undergoing a variety of surgical procedures under general anaesthesia were studied prospectively. Preoperatively, they completed a questionnaire concerning potential risk factors for the occurrence of PV or PONV implemented in the three risk scores. Balanced anaesthesia (induction agent, nondepolarising neuromuscular blocker, opioid, and inhalation agent in nitrous oxide/oxygen) was performed. No intravenous anaesthesia or any antiemetic prophylaxis was applied. Postoperatively, the patients were observed in the recovery room for the occurrence of PV and PONV and were visited twice on the ward within the 24-h observation period. Both the patients and the nursing staff were asked whether PV or PONV was present. The severity of PONV was categorised using a standardised scoring algorithm. A total of 1,444 patients was finally included into the analysis. Using information of the predicted risk for the individual patients and the actual occurrence of PV or PONV, Receiver Operator Characteristics (ROC-curves) were drawn. The area under each ROC-curve was calculated as a means of the predictive properties of each score and was compared for statistical differences. RESULTS: For prediction of PONV (any severity) the AUC-values (AUC=area under the curve) and the corresponding 95%-confidence intervals were: Apfel: 0.70 (0.67-0.72); Koivuranta: 0.71 (0.69-0.73); Palazzo: 0.68 (0.65-0.70). For prediction of PV: Apfel: 0.73 (0.71-0.75); Koivuranta: 0.73 (0.70-0.75); Palazzo: 0.68 (0.65-0.70). Thus, all three scores appeared to have a moderate accuracy as measured by the AUC. The score of Koivuranta predicts PONV (P=0.007) and also PV (P=0.002) significantly better than Palazzo's score. Furthermore, for predicting of PV the score of Apfel was also superior to Palazzo's score (P=0.005). All three scores predict PV with the same accuracy as PONV. CONCLUSION: The occurrence of PV and PONV in patients undergoing surgery under balanced anaesthesia can be predicted with moderate but acceptable accuracy using one of the available risk scores, regardless of local surgical or anaesthesiological circumstances. For clinical practice, we recommend the score published by Koivuranta, since its calculation is very simple.

Adult↗

PubMed2000

Correlation of positive RT-PCR for tyrosinase in peripheral blood of malignant melanoma patients with clinical stage, survival and other risk factors.

The clinical value of the reverse transcription polymerase chain reaction (RT-PCR) assay for tyrosinase in peripheral blood of melanoma patients is still under debate. A total of 212 blood samples from 212 melanoma patients in all clinical stages (AJCC) were examined. Erythrocytes were lysed prior to RNA extraction by phenol precipitation from 2.7 ml of blood. cDNA for tyrosinase PCR was synthesized using random hexamers. Positive tyrosinase RT-PCR results were obtained in 11% of 106 stage I patients, 18% of 56 stage II patients, 31% of 26 stage III patients and 67% of 24 stage IV patients. After a median follow-up of 36 months (range 26-41), stage III patients with positive RT-PCR for tyrosinase had a shortened disease-free interval as compared to negative patients (P < 0.01). In stage IV patients, median overall survival was 8 months in case of a positive RT-PCR in contrast to 12 months in case of a negative test. While univariate analysis showed sex and primary tumour location associated with positive RT-PCR, multiple regression analysis revealed clinical stage and detection of tyrosinase transcripts in peripheral blood as best prognostic factors. Hazard ratios for disease-free survival were 19.7 (confidence interval (CI) 8.53-45.5, P = 0.0001) for metastatic vs primary disease and 2.96 (CI 1.49-5.89, P = 0.002) for positive vs negative tyrosinase RT-PCR. The corresponding hazard ratios for overall survival were 97.0 (CI 12.7-741, P = 0.0001) and 4.33 (CI 1.69-11.1, P= 0.002). Our results emphasize the importance of tyrosinase RT-PCR testing in peripheral blood.

Adult↗

PubMed2000

A quotient of independent measurements as outcome. A statistical method to compare groups in biological experiments.

The methodology in this paper was proposed to analyze biological data. The variable of interest, W, was a quotient of measurements; W: = X/(Y.Z). The peculiar problem was that X, Y, and Z could only be determined in three independent units of observation which were destroyed in the course of each measurement. A test statistic for the comparison of two treatments in W is proposed which is based on robust measures of location and dispersion in order to account for outliers in the data. Simulations showed that the test statistic proposed is approximately normally distributed, even for small sample sizes.

Algorithms↗

PubMed2000

Hemoglobin A1c and body mass index in children and adolescents with IDDM. An observational study from 1976-1995.

In adult patients with type 1 diabetes good metabolic control was associated with an undesired weight gain. In the present report the possible association of HbA1c and body mass index (BMI) in children and adolescents with type 1 diabetes (IDDM) was investigated in a long-term retrospective study from 1976 to 1995. Further, the relationship between BMI on one hand and age, gender, duration of IDDM, the number of units of insulin used and the number of injections per day on the other hand were considered. Statistical analysis was performed using repeated measurements analyses of variance. The 208 girls and 201 boys were 5-17 years old and had diabetes for beyond one year. For analysis 2512 data sets, in part measurements on the same patient in the course of the disease, were available. In various statistical models, the results show that age, gender, the daily amount of insulin, and the HbA1c level (p<0.001-0.005) were associated with the BMI. Extremely high HbA1c levels coincided with a remarkably low BMI. Hence, in children and adolescents with IDDM it may be difficult to achieve a constantly good metabolic control accompanied by a normal body weight.

Adolescent↗

PubMed1999

Randomized comparison of high-frequency ventilation with high-rate intermittent positive pressure ventilation in preterm infants with respiratory failure.

OBJECTIVE: In a randomized, controlled, multicenter trial, we tested the hypothesis that high-frequency ventilation (HFV) with a high lung volume strategy results in fewer treatment failures than intermittent positive pressure ventilation (IPPV) with high rates and low peak inspiratory pressures. STUDY DESIGN: Infants with a gestational age between >/=24 weeks and <30 weeks, requiring mechanical ventilation within 6 hours of birth, were randomly assigned to receive either IPPV or HFV until 240 hours after randomization, extubation, or meeting treatment failure criteria. Treatment failure, the primary end point, was determined when air leaks, an oxygenation index >35 to 45 (depending on gestational age), death, or chronic lung disease occurred. Chronic lung disease was defined as persistent requirement of mechanical ventilation, continuous positive airway pressure, or supplemental oxygen at a postmenstrual age of 36 weeks. Secondary end points included the incidence of intracranial hemorrhage. RESULTS: The third scheduled interim analysis led to termination of the trial after recruitment of 284 infants. Treatment failure criteria were met by 46% of infants receiving IPPV and 54% of infants receiving HFV (1-tailed primary hypothesis, P =.92; 2-tailed chi2 test, P =.15). Air leaks occurred in 31% and 42% (P =.042), CLD in 23% and 25%, and grade 3-4 intracranial hemorrhage in 13% and 14% of IPPV-treated and HFV-treated patients, respectively. The mortality rate before discharge was 10% in both groups. CONCLUSION: HFV with a high lung volume strategy did not cause less lung injury in preterm infants than IPPV with a high rate and low peak inspiratory pressures.

Bronchopulmonary Dysplasia↗

PubMed1999

The procedure of new drug application and the philosophy of critical rationalism or the limits of quality assurance with good clinical practice.

K.R. Popper's philosophy of critical rationalism is concerned with the detection and removal of error. Fundamental contradictions exist between Popper's theory of knowledge and the present-day practice of the clinical investigation of new drugs. Currently, the public authorities concerned with the licensing of drugs pass judgment on trials, which are closely linked by the one-sponsor problem: the assertions made by the sponsor are not independently confirmed. This lack leads to excessive documentation and to costly monitoring and auditing, which are intended to ensure the credibility of results. In Popper's view, confirmatory trials, independent of the sponsor and supervised by the regulatory bodies, would be a better way to achieve reliable knowledge. The consequence would, among other things, be a reorganization of phase III of the clinical investigation of new drugs by dividing it into independent parts, one under the control of the sponsor and one under the control of the public authority. The implementation of this suggestion would lead to a more scientific manner of dealing with new drugs and to savings in terms of unproductive measures during the application process.

Clinical Trials, Phase III as Topic↗

PubMed1999

Cardiac changes in fetuses secondary to immune hemolytic anemia and their relation to hemoglobin and catecholamine concentrations in fetal blood.

OBJECTIVES: Immune hemolytic anemia in the fetus may cause cardiac decompensation and intrauterine death. Postnatally, norepinephrine (noradrenaline) is released in chronic heart failure, and may lead to myocardial hypertrophy. The aim of this study was to determine fetal cardiac changes associated with immune hemolytic anemia by means of echocardiography, and to relate them to fetal hemoglobin and norepinephrine levels. DESIGN: Thirty anemic fetuses underwent a total of 76 umbilical venous transfusions. Before the procedure, fetal echocardiography was performed, and end-diastolic myocardial wall thicknesses and ventricular dimensions together with Doppler flow patterns at the atrioventricular and semilunar valves were measured. Fetal hemoglobin, epinephrine and norepinephrine concentrations were determined before the transfusion. Statistical analysis of this prospective study comprised descriptive statistics including linear regression and correlation analyses. Two samples of measurements were compared by the Mann-Whitney U test. RESULTS: The mean hemoglobin concentration before the first transfusion was 6.9 g% at a mean gestational age of 26.8 weeks. Norepinephrine values were elevated in comparison to a reference range, and were higher than epinephrine values. The most striking echocardiographic finding was myocardial hypertrophy of all ventricular walls. Mean blood flow velocities were increased; at the left ventricle, they were negatively related to the hemoglobin concentrations, and positively to the norepinephrine values. CONCLUSIONS: Fetal myocardial hypertrophy in anemia may be the result of an augmented cardiac workload, indicated by the increased left ventricular mean velocities. This reaction reflects the redistribution of blood flow that may depend on hemoglobin and norepinephrine concentrations.

Anemia, Hemolytic, Autoimmune↗

PubMed1998

Reproducibility of measurements with a new slit lamp-mounted ocular blood flow tonograph.

PURPOSE: To assess the reliability of measurements of intraocular pressure (i.o.p.), pulse amplitude (PA), and pulsatile ocular blood flow (POBF) and the validity of measurements of IOP with a new ocular blood flow tonograph. METHODS: Intraocular pressure pulse was assessed with pneumatic tonometry. In this study, we used the OBF Labs ocular blood flow tonograph with two different pneumatic probes, a modified Langham probe and a newly developed probe. One ophthalmologist compared two machines, first with the modified Langham probe and secondly with the newly developed probe (40 volunteers). Additionally, two ophthalmologists performed measurements on different days and in different sequence (34 volunteers). Furthermore, results of IOP measurements performed with this tonograph were compared to those of Goldmann applanation tonometry (213 volunteers). RESULTS: Using the modified Langham probe, POBF and PA were associated with the machine used for the test. However, using the newly developed pobe, no relevant or statistically significant differences were found for any variables, and reliability coefficients were between 0.70 and 0.90. Linear regression analysis of the Goldmann applanation tonometer on the measurements of IOP with the tonograph showed a regression coefficient of 0.765. CONCLUSIONS: Results of measurements performed with this ocular blood flow tonograph and the newly developed probe are expected to be reliable and comparable.

Adolescent↗

PubMed1998

Randomized observational studies on the economics of therapies--biometrical experience of two trials.

Economic studies in medicine are intended to investigate costs, associated with a particular problem dealing with the indication, diagnosis or therapy, for instance, whether the high costs involved in a highly intensive or innovative therapy could be balanced by the eventual savings made, due to the shorter periods of treatment. In such situations a randomized controlled trial is necessary to find out which therapy or which therapeutical strategy is least expensive in the long run. Economic studies do, however, present some specific problems. Making a list of all the cost-relevant treatment items can be very laborious, but the use of flat rates and lump sums alone cannot lead to a complete cost analysis. Often, costs between hospitals vary more than between treatment regimens. Early and sudden deaths incur low costs and may bias the results. Furthermore, costs are distributed with a long and heavy upper tail including extreme outliers. This does, in fact, complicate the estimation of the sample size. In this article, these problems are outlined and, with the help of the data obtained from two randomized economic trials in health care, solutions are proposed and discussed.

Costs and Cost Analysis↗

PubMed1997

Quantitative liver function tests as surrogate markers for end-points in controlled clinical trials: a retrospective feasibility study.

Quantitative liver function tests such as the determination of galactose elimination capacity (GEC) or the aminopyrine breath test (ABT) may have the potential to serve as refined entry criteria and surrogate markers for end-points in controlled clinical trials. The magnitude of a statistically detectable difference in test results and the period of observation required to document such a difference must be known to properly design such trials. Therefore, we explored retrospectively the time course of changes in GEC and ABT and their reproducibility from a cohort of patients with alcoholic cirrhosis followed for 12 to 42 months, with a median of 34 months. In 15 patients who stopped drinking, GEC improved significantly by 0.64 mg/min/kg within 1 year (mean; 95% confidence interval [CI]: 0.42; 0.86). In contrast, it deteriorated by 0.53 mg/min/kg within 1 year (95% CI: 0.32; 0.74) in another 17 patients who continued to drink (P < .01). The residual standard deviation of the changes in GEC with respect to the patients' initial values was 0.43 mg/min/kg (95% CI: 0.32; 0.52). In addition, ABT improved significantly by 0.14% dose x kg/mmol CO2 (95% CI: 0.09; 0.18) in the abstinent group, and deteriorated by 0.09% dose x kg/mmol CO2 (95% CI: 0.06; 0.13) in the nonabstinent group (P < .01). The residual standard deviation in the above sense for ABT was 0.08% dose x kg/mmol CO2 (95% CI: 0.06; 0.10). These data indicate that clinical trials with a sample size of n = 20 in each group must achieve absolute differences (ADs) in GEC of 0.6 mg/min/kg and of 0.7 mg/min/kg to reach statistical significance at the 5% and 1% level, respectively. In the present study, a period of 11 and 12 months was necessary to observe such differences. The corresponding results for the ABT are 0.11% dose x kg/mmol CO2 (9 months of follow-up; 5% level) and 0.13% dose x kg/mmol CO2 (11 months of observation; 1% level), respectively. Provided that patients with liver diseases treated with drugs are similar to the abstinent and nonabstinent patients with alcoholic liver disease investigated in this study, such numbers could serve for the planning of controlled clinical trials, in which the control group is likely to deteriorate and the treated group is expected to improve. Trials based on GEC or ABT would require only 37 or 30 patient years of observation compared with a median of 444 patient years (range, 50-2,100 patient years) reported for various published controlled clinical trials using survival analysis.

Adult↗

PubMed1997

Cardiac and extracardiac complications in infants of diabetic mothers and their relation to parameters of carbohydrate metabolism.

UNLABELLED: Despite the current improvement of diabetes care in pregnancy, neonatal complications are still more frequent than in the general population. Even in fetuses of well controlled diabetic mothers, myocardial hypertrophy can be demonstrated although it is not related to maternal metabolic control. The objective of this study was to determine perinatal complications and the course of myocardial hypertrophy in newborns who had been prenatally monitored and to relate the findings to neonatal parameters of carbohydrate metabolism. Perinatal complications and echocardiographic evidence of myocardial hypertrophy were determined in 104 neonates of closely followed diabetic mothers. Cord blood was obtained for determination of insulin, C-peptide and glycosylated fetal haemoglobin (HbF1c). In cases of myocardial hypertrophy, the echocardiographic examinations were repeated until normalisation of the myocardial wall thickness. The most striking finding was myocardial hypertrophy in 25% of the 104 neonates, which predominantly involved the interventricular septum. This is in contrast to the prenatal symmetrical hypertrophy of the ventricular walls and may be explained by perinatal changings of ventricular geometry. There was no sign of outflow tract obstruction, and myocardial hypertrophy resolved within 6 months. Insulin and C-peptide were elevated in the majority of the newborns, whereas HbF1c was significantly decreased. Neither the maternal type of diabetes nor neonatal metabolic data were related to the somatic findings. CONCLUSION: Myocardial hypertrophy still occurs in infants of diabetic mothers despite their good metabolic control reflected by the decreased fraction of glycosylated fetal hemoglobin which points to low fetal blood sugar levels during the last intra-uterine weeks.

Carbohydrates↗

PubMed1997

C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection.

OBJECTIVE: To determine whether C-reactive protein (CRP) can be used as a parameter to identify the time point when antibiotic treatment can safely be discontinued in a defined major subgroup of neonates treated for suspected bacterial infection. PATIENTS: One hundred seventy-six newborns with birth weights of greater than 1500 g and without central lines and mechanical ventilation who had suspected bacterial infection were enrolled in a prospective study. SETTING: Tertiary care neonatal reference center. DESIGN: Serum concentrations of CRP were determined 24 to 48 hours after the first dose of antibiotics. If CRP levels were less than 10 mg/L, infants were considered unlikely to be infected, and the antibiotic treatment was stopped using CRP as the single decision criterion in 84 of 94 newborns (group 1). Infants with CRP levels of 10 mg/L or greater were considered likely to be infected and randomized to two study groups. In 38 of 39 neonates (group 2a), CRP was determined daily, and antibiotic therapy was discontinued as soon as CRP returned to less than 10 mg/L. Forty-three neonates with likely infection (group 2b) were treated for at least 5 days, and relapse rates of bacterial infections were compared between groups 2a and 2b. OUTCOME MEASURES: The primary outcome variable of the study was the number of infectious relapses of the primary infection. This was assessed by the need for a second course of antibiotics within 4 weeks of the first one. The value of CRP for guiding treatment duration was determined by calculating the negative predictive value of CRP with respect to further treatment in study groups 1 and 2a. Treatment durations and relapse incidence in the two groups of neonates with likely infection (groups 2a and 2b) were compared. RESULTS: Within the 4-week follow-up period, one infant in group 1 and no infant in group 2a received a second course of antibiotics for bacterial infection. CRP levels of less than 10 mg/L determined later than 24 hours after beginning the antibiotic treatment thus correctly identified 120 of 121 infants as not needing further antibiotics. This corresponds to a negative predictive value with respect to further treatment of 99% (95% confidence interval, 95.4% to 99.9%). The mean treatment duration was 3.7 (median, 4; range, 3 to 6) days in the CRP-guided group and 5.5 (median, 5; range, 5 to 7) days in the at least 5-day study group. In the latter group, one infant was treated for a potential relapse, and one infant was treated for a likely relapse. The low relapse rates in both treatment groups are a preliminary indication that relapses may not occur more frequently if patients are treated until CRP is negative rather than for a 5-day or longer treatment period. CONCLUSIONS: We conclude that CRP could be a key parameter for individually guiding the duration of antibiotic treatment in a major subgroup of newborns with suspected bacterial infection. This approach would allow considerably shorter courses of antibiotic therapy.

Anti-Bacterial Agents↗

PubMed1996

Influence of age, comorbidity, type of operation and other variables on lethality and duration of post-operative hospital stay in patients with peptic ulcer. An analysis of 303 surgically treated patients.

Three hundred and three consecutive patients operated on for peptic ulcer for the first time between 1 January 1984 and 31 December 1993 were evaluated in this retrospective study. Eleven variables (Period when operation took place, gender, smoking behaviour, history of former ulcers, ulcerogenic drug intake, ulcer location, epigastric pain, number of blood units substituted, patient's age, type of operation, comorbidity) were investigated regarding their influence on peri- and post-operative mortality and on the length of hospital stay after operation. We found that a high comorbidity score (> 2) and the indication "emergency operation" (vs "elective operation") had an adverse impact on survival. The importance of age was marginal. The duration of post-operative hospital stay in survivors was negatively influenced by age higher than 60 years, more than two red cell units substituted and a high comorbidity score according to Charlson.

Adult↗

PubMed1995

Relative risks of age, gender, nationality, smoking, and Helicobacter-pylori-infection in duodenal and gastric ulcer and interactions.

A logistic regression model was applied to assess risk factors and diagnostic predictors in duodenal and gastric ulcer, as well as in unspecific changes of gastric mucosa. In the latter group smoking, epigastric distress, and pain were associated with elevated relative risks. In the gastric ulcer model, increased odds were found for age, German nationality, smoking, and low and high urease activity of antral mucosa. This holds for duodenal ulcer, too; however interactions between complaints, urease activity, and nationality must be considered. In each case odds depend from the composition of the control group. Therapeutic implications have been considered.

Adult↗

PubMed1995

Studies on the efficacy of unconventional therapies. Problems and designs.

Many unconventional therapies (e.g. dietary, phytotherapy, acupuncture, homeopathy) are well known and often applied, but their efficacy has hardly been proven. New trial designs and study components must be found to meet the specific demands of the particular unconventional therapy on one hand and keep the high methodological standard of controlled clinical trials on the other hand. Biometricians and unconventional therapists are challenged to develop such designs. Typical problems in designing studies of unconventional therapies include that placebo is not possible, therapies cannot be masked, outcome variables are not reliable, therapy is highly individualized, and studies on the efficacy of soft therapies require many patients and long treatment periods. Studies with unconventional therapies should be performed by practitioners (because they use these therapies), but this leads to further problems. Some solutions are given in examples: A study is described investigating the herbal remedy Kava-Kava for patients in the state of anxiety, tension and restlessness; a study on classical homeopathy for chronical headaches is specified; some designs for dietary studies in patients with rheumatoid arthritis are compared. A design called "cross-allocation of patients to two treatments with randomization option" and the "N-of-1 design", also called "single case design" are described and discussed. The "change-to-open-label design" could be useful to investigate soft and natural therapies which require studies with many patients and long-term treatment.

Arthritis, Rheumatoid↗

PubMed1994

Change-to-Open-Label Design. Proposal and discussion of a new design for clinical parallel-group double-masked trials.

The "Change-to-Open-Label Design" (COLA-design) is proposed to overcome some of the ethical and organizational problems of the usual double-masked design in certain situations while preserving its scientific rigor. Patients are randomized on a doubled-masked basis into treatment groups. During the trial the patient or the treating physician may ask for a change from the masked treatment to any open-label treatment of their choice (experimental or not), if the masked treatment is thought to be unsatisfactory. It seems to be easier to obtain a patient's informed consent to participate in placebo controlled double-masked trials especially for long term studies. The main outcome variable in COLA-design is the time until a patient demands for such a change. "Survival analysis" is a powerful statistical method to evaluate this outcome variable. Even patients lost from observation can be included in the evaluation: they still deliver censored outcome values. Evidently, in trials with a COLA-design the patient's personal impression of the therapy is the most important factor in its assessment. Therapeutical success is mingled with undesirable effects into the outcome measure; therefore this design is especially applicable to investigate treatments supposed to increase quality of life.

Double-Blind Method↗