Boosting enrolment in clinical trials: validation of a regional network model.

BACKGROUND: Clinical trials of stroke therapy have been hampered by slow rates of enrolment. PURPOSE: Our purpose is to validate a previously developed model for accelerating enrolment in clinical trials by replicating it at new locations. The model employs coordinators who travel from a host institution to enrol participants from a network of participating hospitals. Active surveillance assures identification of all eligible patients. METHODS: Among 70 U.S. investigators participating in National Institutes of Health-funded trial of stroke prevention, five investigators were invited to develop local identification and outreach networks (LIONs). Each LION comprised a LION coordinating centre servicing multiple hospitals. Hospitals provided names of patients with stroke or transient ischaemic attack to researchers at the LION coordinating centre who initiated contact; patients were offered home visits for consent and randomization. Outcomes were feasibility, enrolment, data quality, and cost. RESULTS: Five LIONs varied in size from two to eight hospitals. All 24 hospitals we approached agreed to participate. The average monthly rate of enrolment at the research sites increased from 1.4 participants to 3.5 after expanding from a single institution model to the LION format (mean change = 2.1, range 0.9-3.7). Monthly performance improved over time. Data quality was similar for LIONs and non-LION sites, except for drug adherence which was lower at LIONs. The average cost to randomize and follow one participant during the study interval was 2.4 times the cost under the per-patient, cost-reimbursement strategy at non-LION sites. The cost ratio declined from 3.4 in year one to 1.8 in year two. LIMITATIONS: The LION strategy requires unprecedented collaboration and trust among institutions. Applicability beyond stroke requires confirmation. CONCLUSION: LIONs are a practical, reproducible method to increase enrolment in trial research. Twelve months were required for the average site to reach its potential. The per-participant cost at LIONs was higher than conventional sites but declined over time.

Boosting enrollment in neurology trials with Local Identification and Outreach Networks (LIONs).

OBJECTIVE: Our purpose was to develop a geographically localized, multi-institution strategy for improving enrolment in a trial of secondary stroke prevention. METHODS: We invited 11 Connecticut hospitals to participate in a project named the Local Identification and Outreach Network (LION). Each hospital provided the names of patients with stroke or TIA, identified from electronic admission or discharge logs, to researchers at a central coordinating center. After obtaining permission from personal physicians, researchers contacted each patient to describe the study, screen for eligibility, and set up a home visit for consent. Researchers traveled throughout the state to enroll and follow participants. Outside the LION, investigators identified trial participants using conventional recruitment strategies. We compared recruitment success for the LION and other sites using data from January 1, 2005, through June 30, 2007. RESULTS: The average monthly randomization rate from the LION was 4.0 participants, compared with 0.46 at 104 other Insulin Resistance Intervention after Stroke (IRIS) sites. The LION randomized on average 1.52/1,000 beds/month, compared with 0.76/1,000 beds/month at other IRIS sites (p = 0.03). The average cost to randomize and follow one participant was $8,697 for the LION, compared with $7,198 for other sites. CONCLUSION: A geographically based network of institutions, served by a central coordinating center, randomized substantially more patients per month compared with sites outside of the network. The high enrollment rate was a result of surveillance at multiple institutions and greater productivity at each institution. Although the cost per patient was higher for the network, compared with nonnetwork sites, cost savings could result from more rapid completion of research.

Prescribing analysis and cost tabulation (PACT) data: an introduction.

PACT (prescribing analysis and cost tabulation) data is a national data set which analyses prescribing data in terms of cost and number of items (volume). At an organizational level, PACT is used to monitor and control prescribing cost and to set prescribing budgets. At individual practitioner level, it is used as an educational and audit tool. The Prescription Pricing Authority (PPA) has sent general practitioners (GPs) quarterly summary reports of their own prescribing since 1988. From 2000 prescriptions written by nurse prescribers have been added to the national PACT data set, and health authorities, practices and trusts will now be analysing both nurse and GP prescribing quality. Because of differences in the way they work, nurse prescribers will not automatically receive individual reports of their own prescribing. However they should be able to access this information on request through their local health authority prescribing advisers and primary care group pharmacists. Based on GP experience, nurse prescribers should find PACT data a useful learning resource for individual and team practice development.

'Brown bag' medication reviews as a means of optimizing patients' use of medication and of identifying potential clinical problems.

BACKGROUND: 'Brown bag' medication reviews carried out by community pharmacists collaborating with GPs have become established, in the USA and elsewhere, as an effective means of helping primary care patients to derive maximum benefit from their medicines, of identifying medication-related problems and of reducing wastage of medicines. OBJECTIVE: We aimed to determine whether 'brown bag' medication review could be used successfully in the UK, and particularly whether it represents an efficient and potentially cost-effective means of identifying medication problems. METHOD: 'Brown bag' medication reviews were carried out on 205 volunteer patients in 23 pharmacies in south-east London. Pharmacists' interventions to improve patients' knowledge and usage of their medicines were analysed. Potential clinical problems identified by pharmacists were analysed in order to identify the drug groups most likely to cause problems. RESULTS: Interventions were made in 87% of reviews; interventions to improve patients' knowledge of the purpose and correct usage of their drugs were made in 65% of reviews. In 12% of reviews, problems were identified that could potentially result in a hospital admission, and the potential for an improved outcome for the patient if drug therapy was changed was identified in a further 34% of cases. Beta-blockers, NSAIDs and verapamil were identified as being associated with potential problems of the highest clinical significance. Patients taking psychoactive medication were at greatest risk of a medication-related problem from any cause. CONCLUSION: Pharmacists could contribute to patients' welfare and reduce health care costs by carrying out 'brown bag' medication reviews on behalf of GPs.

A bacteriophage lambda vector for the cloning and expression of immunoglobulin Fab fragments on the surface of filamentous phage.

We have combined the high cloning efficiency of the lambda bacteriophage vectors with the surface expression screening method for the display of combinatorial antibody fragment (Fab) libraries on the surface of filamentous phage particles. The utility of the herein described ImmunoZAP 13 system for the isolation of Fabs that specifically bind antigen is demonstrated using two phagemid display libraries prepared from a previously characterized human combinatorial library. The percentage of clones that specifically bind antigen is maintained throughout the process of subcloning the LC and VH genes into ImmunoZAP 13, in vivo mass excision to convert the lambda library to a phagemid library, and preparation of phagemid particles displaying Fabs. Specific phagemid were isolated from libraries containing 0.6% and 0.03% tetanus toxoid (TT)-binding clones after two and three rounds of biopanning, respectively. Relative binding curves determined on a small sample of isolated clones indicate that several unique immunoglobulin Fab fragments have been isolated.