Application of Incident Command Structure to clinical trial management in the academic setting: principles and lessons learned

Background Clinical trial success depends on appropriate management, but practical guidance to trial organisation and planning is lacking. The Incident Command System (ICS) is the ‘gold standard’ management system developed for managing diverse operations in major incident and public health arenas. It enables effective and flexible management through integration of personnel, procedures, resources, and communications within a common hierarchical organisational structure. Conventional ICS organisation consists of five function modules: Command, Planning, Operations, Logistics, and Finance/Administration. Large clinical trials will require a separate Regulatory Administrative arm, and an Information arm, consisting of dedicated data management and information technology staff. We applied ICS principles to organisation and management of the Prehospital Use of Plasma in Traumatic Haemorrhage (PUPTH) trial. This trial was a multidepartmental, multiagency, randomised clinical trial investigating prehospital administration of thawed plasma on mortality and coagulation response in severely injured trauma patients. We describe the ICS system as it would apply to large clinical trials in general, and the benefits, barriers, and lessons learned in utilising ICS principles to reorganise and coordinate the PUPTH trial. Results Without a formal trial management structure, early stages of the trial were characterised by inertia and organisational confusion. Implementing ICS improved organisation, coordination, and communication between multiple agencies and service groups, and greatly streamlined regulatory compliance administration. However, unfamiliarity of clinicians with ICS culture, conflicting resource allocation priorities, and communication bottlenecks were significant barriers. Conclusions ICS is a flexible and powerful organisational tool for managing large complex clinical trials. However, for successful implementation the cultural, psychological, and social environment of trial participants must be accounted for, and personnel need to be educated in the basics of ICS

The reverse protraction factor in the induction of bone sarcomas in radium-224 patients

More than 50 bone sarcomas have occurred among a collective of about 800 patients who had been injected in Germany after World War II with large activities of radium-224 for the intended treatment of bone tuberculosis and ankylosing spondylitis.^In an earlier analysis it was concluded that, at equal mean absorbed doses in the skeleton, patients with longer exposure time had a higher incidence of bone sarcomas.^The previous analysis was based on approximations; in particular, it did not account for the varying times at risk of the individual patients.^In view of the implications of a reverse protraction factor for basic considerations in radiation protection, the need was therefore felt to reevaluate the data from the continued follow-up by more rigorous statistical methods.^A first step of the analysis demonstrates the existence of the reverse dose-rate effect in terms of a suitably constructed rank-order test.^In a second step of the analysis it is concluded that the data are consistent with a linear no-threshold dose dependence under the condition of constant exposure time, while there is a steeper than linear dependence on dose when the exposure times increase proportionally to dose.^A maximum likelihood fit of the data is then performed in terms of a proportional hazards model that includes the individual parameters, dose, treatment duration, and age at treatment.^The fit indicates proportionality of the tumor rates to mean skeletal dose with an added factor (1 + 0.18.tau), where tau is the treatment time in months.^This indicates that a protraction of the injections over 15 months instead of 5 months doubles the risk of bone sarcoma

Analysis of a method for precisely relating a seafloor point to a distant point on land

A study of the environmental constraints and engineering aspects of the acoustic portion of a system for making geodetic ties between undersea reference points and others on land is described. Important areas in which to make such observations initially would be from the California mainland out to oceanic points seaward of the San Andreas fault, and across the Aleutian Trench. The overall approach would be to operate a GPS receiver in a relative positioning (interferometric) mode to provide the long range element of the baseline determination (10 to 1,000 km) and an array of precision sea floor acoustic transponders to link the locally moving sea surface GPS antenna location to a fixed sea floor point. Analyses of various environmental constrants (tides, waves, currents, sound velocity variations) lead to the conclusion that, if one uses a properly designed transponder having a remotely controllable precise retransmission time delay, and is careful with regard to methods for installing these on the sea floor, one should, in many ocean locations, be able to achieve sub-decimeter overall system accuracy. Achievements of cm accuracy or better will require additional understanding of time and space scales of variation of sound velocity structure in the ocean at relevant locations

An epidemiological assessment of lens opacifications that impaired vision in patients injected with radium-224

The incidence of lens opacifications that impaired vision (cataract) was analyzed among 831 patients who were injected with known dosages of 224Ra in Germany shortly after World War II. The dependence of the incidence on dosage, i.e., injected activity per unit body weight, and on time after treatment was determined. The observations are equally consistent with proportionality of the incidence of cataract to the square of dosage or with a linear dependence beyond a threshold of 0.5 MBq/kg. The possibility of a linear dependence without threshold was strongly rejected (P less than 0.001). The analysis of temporal dependences yielded a component that was correlated with the injected amount of 224Ra and a component that was uncorrelated. The former was inferred by a maximum likelihood analysis to increase approximately as the square of the time after treatment. The component unrelated to the treatment was found to increase steeply with age and to become dominant within the collective of patients between age 50 and 60. The relative magnitudes of the two components were such that a fraction of 55 to 60% of the total of 58 cataracts had to be ascribed to the dose-related incidence. Impaired vision due to cataract was diagnosed before age 54 in 25 cases. In terms of injected activity per unit body weight no dependence of the sensitivity on age was found; specifically there was no indication of a faster occurrence of the treatment-related cataracts in patients treated at older ages

Bone sarcoma cumulative tumor rates in patients injected with 224Ra

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Method and system for measuring sound velocity

A method and system for determining the speed of sound in a fluidic medium by determining the travel time of an acoustical signal a predetermined distance in a fluidic medium by generating a cyclical reference signal of a predetermined frequency and transmitting a portion of the reference signal through the medium. The transmitted portion of the reference signal is received after travelling a predetermined distance in the fluidic medium. The cycles of the cyclical reference signal are counted during the period of time between the transmitting and receiving of the portion of the reference signal wherein the travel time of the portion of the reference signal, is the number of cycle counts divided by the frequency. The speed of the acoustical signal through the fluidic medium is a function of the path length divided by the travel time

Time and dose dependency of bone-sarcomas in patients injected with radium-224

The time course and dose dependency of the incidence of bone-sarcomas among 900 German patients treated with high doses of radium-224 is analysed in terms of a proportional hazards model with a log-normal dependency of time to tumor and a linear-quadratic dose relation. The deduced dose dependency agrees well with a previous analysis in terms of a non-parametric proportional hazards model, and confirms the temporal distribution which has been used in the Radioepidemiological Tables of NIH. However, the linear-quadratic dose-response model gives a risk estimate for low doses which is somewhat less than half that obtained under the assumption of linearity. Dedicated to Prof. W. Jacobi on the occasion of his 60th birthday Work performed under Euratom contracts BI6-D-083-D, BI6-F-111-D, U.S. Department of Energy contract DE-AC 02-76 EV-00119, the U.S. National Cancer Institut