Metabolite Bioanalysis in Drug Development: Recommendations from the IQ Consortium Metabolite Bioanalysis Working Group.

The intent of this perspective is to share the recommendations of the International Consortium for Innovation and Quality in Pharmaceutical Development Metabolite Bioanalysis Working Group on the fit-for-purpose metabolite bioanalysis in support of drug development and registration. This report summarizes the considerations for the trigger, timing, and rigor of bioanalysis in the various assessments to address unique challenges due to metabolites, with respect to efficacy and safety, which may arise during drug development from investigational new drug (IND) enabling studies, and phase I, phase II, and phase III clinical trials to regulatory submission. The recommended approaches ensure that important drug metabolites are identified in a timely manner and properly characterized for efficient drug development.

Neutralization Activity of Anti-drug Antibodies Against a Biotherapeutic Can Be Predicted from a Comprehensive Pharmacokinetics, Pharmacodynamics, and Anti-drug Antibody Data Analysis.

Historically, a neutralization antibody (NAb) assay is considered critical in immunogenicity assessment of biologic therapeutics, even with low anti-drug antibody (ADA) positive rates. In 2019, FDA new guidelines issued on immunogenicity testing acknowledged the possibility of using "a highly sensitive PD marker or an appropriately designed PK assay or both that generate data that inform clinical activity" to replace a NAb assay. In the current manuscript, we present data for PK, PD, and ADA assays which collectively succeed to replace the standalone NAb assay. The data include a total LC/MS-based PK assay, a serum neutralization antibody (SNA) assay that essentially measures pharmacodynamically functional PK and can detect NAb activity in the presence of 1:1 ratio of drug, and a highly drug-tolerant ADA assay. In addition, a model-based meta-analysis (MBMA) demonstrated that the ability of SNA assay to detect NAb at 1:1 ratio of drug is sensitive enough to monitor clinically meaningful efficacy change, which is 50% reduction of SNA titer. Our strategy of preparing a holistic data package discussed here may provide a roadmap to the community for alternatives in assaying neutralizing activity of ADA.

What happens in the brain?

A new imaging method reveals previously undetected structural differences that may contribute to developmental language disorder.

Biomarker Assay Validation by Mass Spectrometry.

Decades of discussion and publication have gone into the guidance from the scientific community and the regulatory agencies on the use and validation of pharmacokinetic and toxicokinetic assays by chromatographic and ligand binding assays for the measurement of drugs and metabolites. These assay validations are well described in the FDA Guidance on Bioanalytical Methods Validation (BMV, 2018). While the BMV included biomarker assay validation, the focus was on understanding the challenges posed in validating biomarker assays and the importance of having reliable biomarker assays when used for regulatory submissions, rather than definition of the appropriate experiments to be performed. Different from PK bioanalysis, analysis of biomarkers can be challenging due to the presence of target analyte(s) in the control matrices used for calibrator and quality control sample preparation, and greater difficulty in procuring appropriate reference standards representative of the endogenous molecule. Several papers have been published offering recommendations for biomarker assay validation. The situational nature of biomarker applications necessitates fit-for-purpose (FFP) assay validation. A unifying theme for FFP analysis is that method validation requirements be consistent with the proposed context of use (COU) for any given biomarker. This communication provides specific recommendations for biomarker assay validation (BAV) by LC-MS, for both small and large molecule biomarkers. The consensus recommendations include creation of a validation plan that contains definition of the COU of the assay, use of the PK assay validation elements that support the COU, and definition of assay validation elements adapted to fit biomarker assays and the acceptance criteria for both.

Consolidation of vocabulary is associated with sleep in typically developing children, but not in children with dyslexia.

Sleep is known to play an active role in consolidating new vocabulary in adults; however, the mechanisms by which sleep promotes vocabulary consolidation in childhood are less well understood. Furthermore, there has been no investigation into whether previously reported differences in sleep architecture might account for variability in vocabulary consolidation in children with dyslexia. Twenty-three children with dyslexia and 29 age-matched typically developing peers were exposed to 16 novel spoken words. Typically developing children showed overnight improvements in novel word recall; the size of the improvement correlated positively with slow wave activity, similar to previous findings with adults. Children with dyslexia showed poorer recall of the novel words overall, but nevertheless showed overnight improvements similar to age-matched peers. However, comparisons with younger children matched on initial levels of novel word recall pointed to reduced consolidation in dyslexics after 1 week. Crucially, there were no significant correlations between overnight consolidation and sleep parameters in the dyslexic group. This suggests a reduced role of sleep in vocabulary consolidation in dyslexia, possibly as a consequence of lower levels of learning prior to sleep, and highlights how models of sleep-associated memory consolidation can be usefully informed by data from typical and atypical development.

Comorbidity profile and healthcare utilization in elderly patients with serious mental illnesses.

OBJECTIVES: Patients with serious mental illness are living longer. Yet, there remain few studies that focus on healthcare utilization and its relationship with comorbidities in these elderly mentally ill patients. DESIGN: Comparative study. Information on demographics, comorbidities, and healthcare utilization was taken from an electronic medical record system. SETTING: Wishard Health Services senior care and community mental health clinics. PARTICIPANTS: Patients age 65 years and older-255 patients with serious mental illness (schizophrenia, major recurrent depression, and bipolar illness) attending a mental health clinic and a representative sample of 533 nondemented patients without serious mental illness attending primary care clinics. RESULTS: Patients having serious mental illness had significantly higher rates of medical emergency department visits (p = 0.0027) and significantly longer lengths of medical hospitalizations (p <0.0001) than did the primary care control group. The frequency of medical comorbidities such as diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, thyroid disease, and cancer was not significantly different between the groups. Hypertension was lower in the mentally ill group (p <0.0001). Reported falls (p <0.0001), diagnoses of substance abuse (p = 0.02), and alcoholism (p = 0.0016) were higher in the seriously mentally ill. The differences in healthcare utilization between the groups remained significant after adjusting for comorbidity levels, lifestyle factors, and attending primary care. CONCLUSIONS: Our findings of higher rates of emergency care, longer hospitalizations, and increased frequency of falls, substance abuse, and alcoholism suggest that seriously mentally ill older adults remain a vulnerable population requiring an integrated model of healthcare.

Cognitive impairment: an independent predictor of excess mortality: a cohort study.

BACKGROUND: Dementia is a leading cause of death among older adults, but less is known about the mortality risk associated with milder forms of cognitive impairment. OBJECTIVE: To determine whether cognitive impairment is independently associated with increased long-term mortality in primary care patients aged 60 years and older. DESIGN: Linkage of electronic health records from a cohort recruited between January 1991 and May 1993 with data from the National Death Index through 31 December 2006. SETTING: A public safety-net hospital and its community health centers. PATIENTS: 3957 older adults aged 60 to 102 years who were screened at scheduled primary care appointments. MEASUREMENTS: At baseline, patients were screened for cognitive impairment by using the Short Portable Mental Status Questionnaire and were categorized into groups with no, mild, or moderate to severe cognitive impairment. Baseline data from comprehensive electronic health records were linked with vital status obtained from the National Death Index. Kaplan-Meier survival curves compared time to death for the groups with cognitive impairment. Cox proportional hazards models controlled for mortality risk factors. RESULTS: At baseline, 3157 patients had no cognitive impairment, 533 had mild impairment, and 267 had moderate to severe impairment. Overall, 2385 of the 3957 patients (60.3%) died during the observation period: 1812 (57.4%) patients with no cognitive impairment, 363 (68.1%) patients with mild impairment, and 210 (78.7%) patients with moderate to severe impairment. Both mild and moderate to severe cognitive impairment were associated with increased mortality hazard independent of other mortality risk factors (hazard ratio, 1.184 [95% CI, 1.051 to 1.334] and for mild impairment 1.447 [CI, 1.235 to 1.695] for moderate to severe impairment). Median survival for all 3957 participants was 129 months. Median survival for participants with no, mild, and moderate to severe cognitive impairment was 138, 106, and 63 months, respectively. LIMITATIONS: Cognition was assessed only at enrollment by using a screening instrument. Participants were drawn from a single safety-net health system and had low educational and socioeconomic status, which limits generalizability to other populations. Changes in cognition, function, and comorbid conditions were not measured over time. CONCLUSION: Both mild and moderate to severe cognitive impairment as identified by the Short Portable Mental Status Questionnaire are associated with an increased risk for mortality. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Screening, referral, and participation in a weight management program implemented in five CHCs.

Community health centers have the potential to lessen obesity. We conducted a retrospective evaluation of a quality improvement program that included electronic body mass index (BMI) screening with provider referral to an in-clinic lifestyle behavior change counselor with weekly nutrition and exercise classes. There were 26,661 adult patients seen across five community health centers operating the weight management program. There were 23,593 (88%) adult patients screened, and 12,487 (53%) of these patients were overweight or obese (BMI >or=25). Forty percent received a provider referral, 15.6% had program contact, and 2.1% had more than 10 program contacts. A mean weight loss of seven pounds was observed among those patients with more than 10 program contacts. No significant weight change was observed in patients with less contact. Achieving public health impact from guideline recommended approaches to CHC-based weight management will require considerable improvement in patient and provider participation.

Pharmacist intervention to improve medication adherence in heart failure: a randomized trial.

BACKGROUND: Patients with heart failure who take several prescription medications sometimes have poor adherence to their treatment regimens. Few interventions designed to improve adherence to therapy have been rigorously tested. OBJECTIVE: To determine whether a pharmacist intervention improves medication adherence and health outcomes compared with usual care for low-income patients with heart failure. DESIGN: Randomized, controlled trial conducted from February 2001 to June 2004. SETTING: University-affiliated, inner-city, ambulatory care practice. PATIENTS: 314 low-income patients 50 years of age or older with heart failure confirmed by their primary care physician. INTERVENTION: Patients were randomly assigned to intervention (39% [n = 122]) or usual care (61% [n = 192]) groups and were followed for 12 months. A pharmacist provided a 9-month multilevel intervention, with a 3-month poststudy phase. An interdisciplinary team of investigators designed the intervention to support medication management by patients who have low health literacy and limited resources. MEASUREMENTS: Primary outcomes were adherence, as measured by using electronic prescription monitors, and exacerbations requiring emergency department care or hospital admission. Secondary outcomes included health-related quality of life, patient satisfaction with pharmacy services, and total direct costs. RESULTS: During the 9-month intervention period, medication adherence was 67.9% and 78.8% in the usual care and intervention groups, respectively (difference, 10.9 percentage points [95% CI, 5.0 to 16.7 percentage points]). However, these salutary effects dissipated in the 3-month postintervention follow-up period, in which adherence was 66.7% and 70.6%, respectively (difference, 3.9 percentage points [CI, -5.9 to 6.5 percentage points]). Medications were taken on schedule 47.2% of the time in the usual care group and 53.1% of the time in the intervention group (difference, 5.9 percentage points [CI, 0.4 to 11.5 percentage points]), but this effect also dissipated at the end of the intervention (48.9% vs. 48.6%, respectively; difference, 0.3 percentage point [CI, -5.9 to 6.5 percentage points]). Emergency department visits and hospital admissions were 19.4% less (incidence rate ratio, 0.82 [CI, 0.73 to 0.93]) and annual direct health care costs were lower ($-2960 [CI, $-7603 to $1338]) in the intervention group. LIMITATIONS: Because electronic monitors were used to ascertain adherence, patients were not permitted to use medication container adherence aids. The intervention involved 1 pharmacist and a single study site that served a large, indigent, inner-city population of patients. Because the intervention had several components, intervention effects could not be attributed to a single component. CONCLUSIONS: A pharmacist intervention for outpatients with heart failure can improve adherence to cardiovascular medications and decrease health care use and costs, but the benefit probably requires constant intervention because the effect dissipates when the intervention ceases. ClinicalTrials.gov registration number: NCT00388622.

An electronic medical record system for ambulatory care of HIV-infected patients in Kenya.

Administering and monitoring therapy is crucial to the battle against HIV/AIDS in sub-Saharan Africa. Electronic medical records (EMRs) can aid in documenting care, monitoring drug adherence and response to therapy, and providing data for quality improvement and research. Faculty at Moi University in Kenya and Indiana and University in the USA opened adult and pediatric HIV clinics in a national referral hospital, a district hospital, and six rural health centers in western Kenya using a newly developed EMR to support comprehensive outpatient HIV/AIDS care. Demographic, clinical, and HIV risk data, diagnostic test results, and treatment information are recorded on paper encounter forms and hand-entered into a central database that prints summary flowsheets and reminders for appropriate testing and treatment. There are separate modules for monitoring the Antenatal Clinic and Pharmacy. The EMR was designed with input from clinicians who understand the local community and constraints of providing care in resource poor settings. To date, the EMR contains more than 30,000 visit records for more than 4000 patients, almost half taking antiretroviral drugs. We describe the development and structure of this EMR and plans for future development that include wireless connections, tablet computers, and migration to a Web-based platform.

Behavioral correlates of olfactory and trigeminal gaseous stimulation in chickens, Gallus domesticus.

Despite growing evidence of avian olfactory abilities, there are few reports of behavioral correlates of chemosensory stimulation in birds. The present study aimed to determine how the behavioral responses of hens to selected gases might be affected by input from different chemosensory systems. We also hoped to relate electrophysiological thresholds previously measured in our laboratory to behavioral evidence of perception. Immediate behavioral responses to ascending series of short (7 s) pulses of olfactory (hydrogen sulphide), trigeminal (carbon dioxide) and combining (ammonia) gaseous stimulants were measured in 12 partially restrained adult hens (Gallus domesticus) using a purpose built gas delivery system. The concentration ranges applied matched those used in our previous electrophysiological studies of olfactory bulb responses. Consistent and specific behavioral responses were observed in response to stimulation with each gas. While significant increases in mandibulation (a distinctive rapid bout of bill movements), interruption of ongoing behavior, orientation to the end of the stimulus, and struggling were seen during stimulation with all three gases, orientation towards the stimulus occurred only in response to the olfactory stimulants, ammonia and hydrogen sulphide. The only gas to elicit significant avoidance was hydrogen sulphide, while gasping and headshaking were elevated in response to stimulation with carbon dioxide. Approximate threshold values for some types of behavior related reasonably well to receptor thresholds determined electrophysiologically, but perception may have occurred at lower concentrations without overt behavioral consequences. The diversity of the behavioral responses observed supports the notion that the gases selectively stimulated different sensory pathways.

Can computer-generated evidence-based care suggestions enhance evidence-based management of asthma and chronic obstructive pulmonary disease? A randomized, controlled trial.

OBJECTIVE: Translation of evidence-based guidelines into clinical practice has been inconsistent. We performed a randomized, controlled trial of guideline-based care suggestions delivered to physicians when writing orders on computer workstations. STUDY SETTING: Inner-city academic general internal medicine practice. STUDY DESIGN: Randomized, controlled trial of 246 physicians (25 percent faculty general internists, 75 percent internal medicine residents) and 20 outpatient pharmacists. We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease. Care suggestions concerning drugs and monitoring were delivered to a random half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations. A 2 x 2 factorial randomization of practice sessions and pharmacists resulted in four groups of patients: physician intervention, pharmacist intervention, both interventions, and controls. DATA EXTRACTION/COLLECTION METHODS: Adherence to the guidelines and clinical activity was assessed using patients' electronic medical records. Health-related quality of life, medication adherence, and satisfaction with care were assessed using telephone questionnaires. PRINCIPAL FINDINGS: During their year in the study, patients made an average of five scheduled primary care visits. There were no differences between groups in adherence to the care suggestions, generic or condition-specific quality of life, satisfaction with physicians or pharmacists, medication compliance, emergency department visits, or hospitalizations. Physicians receiving the intervention had significantly higher total health care costs. Physician attitudes toward guidelines were mixed. CONCLUSIONS: Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease.

Methodology of an ongoing, randomized, controlled trial to improve drug use for elderly patients with chronic heart failure.

BACKGROUND: Medications can improve the functioning and health-related quality of life of patients with chronic heart failure (CHF) and reduce morbidity, mortality, and costs of treatment. However, patients may not adhere to therapy. Patients with complex medication regimens and low health literacy are at risk for nonadherence. OBJECTIVE: The primary goal of this project is to develop and assess a multilevel pharmacy-based program to improve patient medication adherence and health outcomes for elderly CHF patients with low health literacy. METHODS: In this 4-year, controlled trial, patients aged 50 years with a diagnosis of CHF who are being treated at Wishard Health Services (Indianapolis, Indiana) are randomly assigned to pharmacist intervention or usual care. Intervention patients receive 9 months of pharmacist support and 3 months of postintervention follow-up. The intervention involves a pharmacist providing verbal and written education, icon-based labeling of medication containers, and therapeutic monitoring. The pharmacist identifies patients' barriers to appropriate drug use, coaches them on overcoming these barriers, and coordinates medication use issues with their primary care providers. Daily updates of relevant monitoring data are delivered via an electronic medical record system and stored in a personal computer system designed to support pharmacist monitoring and facilitate documentation of interventions. To measure medication adherence objectively, electronic monitoring lids are used on all CHF medications for patients in both study groups. Other assessments include self-reported medication adherence, results of echocardiography (eg, ejection fraction), brain natriuretic peptide concentrations, and health-related quality of life. Health services utilization, refill adherence, and cost data derive from electronic medical records. After completion of this study, the data can be used to assess the effectiveness and cost-effectiveness of our intervention. RESULTS: One hundred twenty-two patients have been assigned to receive the intervention and 192 to receive usual care. CONCLUSIONS: Our study aims to improve patients' knowledge and self-management of their medication and to improve medication monitoring in a multilevel pharmacy-based intervention. By doing so, we intend that the intervention will improve the health outcomes of elderly patients with CHF.

Failure of computerized treatment suggestions to improve health outcomes of outpatients with uncomplicated hypertension: results of a randomized controlled trial.

STUDY OBJECTIVE: To assess the effects of evidence-based treatment suggestions for hypertension made to physicians and pharmacists using a comprehensive electronic medical record system. DESIGN: Randomized controlled trial with a 2 x 2 factorial design of physician and pharmacist interventions, which resulted in four groups of patients: physician intervention only, pharmacist intervention only, intervention by physician and pharmacist, and intervention by neither physician nor pharmacist (control). SETTING: Academic primary care internal medicine practice. SUBJECTS: Seven hundred twelve patients with uncomplicated hypertension. MEASUREMENTS AND MAIN RESULTS: Suggestions were displayed to physicians on computer workstations used to write outpatient orders and to pharmacists when filling prescriptions. The primary end point was generic health-related quality of life. Secondary end points were symptom profile and side effects from antihypertensive drugs, number of emergency department visits and hospitalizations, blood pressure measurements, patient satisfaction with physicians and pharmacists, drug therapy compliance, and health care charges. In the control group, implementation of care changes in accordance with treatment suggestions was observed in 26% of patients. In the intervention groups, compliance with suggestions was poor, with treatment suggestions implemented in 25% of patients for whom suggestions were displayed only to pharmacists, 29% of those for whom suggestions were displayed only to physicians, and 35% of the group for whom both physicians and pharmacists received suggestions (p=0.13). Intergroup differences were neither statistically significant nor clinically relevant for generic health-related quality of life, symptom and side-effect profiles, number of emergency department visits and hospitalizations, blood pressure measurements, charges, or drug therapy compliance. CONCLUSION: Computer-based intervention using a sophisticated electronic physician order-entry system failed to improve compliance with treatment suggestions or outcomes of patients with uncomplicated hypertension.

A controlled trial of including symptom data in computer-based care suggestions for managing patients with chronic heart failure.

BACKGROUND: Heart failure is common and associated with considerable morbidity and cost, yet physician adherence to treatment guidelines is suboptimal. We conducted a randomized controlled study to determine if adding symptom information to evidence-based, computer-generated care suggestions would affect treatment decisions among primary care physicians caring for outpatients with heart failure at two Veterans Affairs medical centers. METHODS: Physicians were randomly assigned to receive either care suggestions generated with electronic medical record data and symptom data obtained from questionnaires mailed to patients within 2 weeks of scheduled outpatient visits (intervention group) or suggestions generated with electronic medical record data alone (control group). Patients had to have a diagnosis of heart failure and objective evidence of left ventricular systolic dysfunction. We assessed physician adherence to heart failure guidelines, as well as patients' New York Heart Association (NYHA) class, quality of life, satisfaction with care, hospitalizations, and outpatient visits, at 6 and 12 months after enrollment. RESULTS: Patients in the intervention (n = 355) and control (n = 365) groups were similar at baseline. At 12 months, there were no significant differences in adherence to care suggestions between physicians in the intervention and control groups (33% vs. 30%, P = 0.4). There were also no significant changes in NYHA class (P = 0.1) and quality-of-life measures (P >0.1), as well as no differences in the number of outpatient visits between intervention and control patients (6.7 vs. 7.1 visits, P = 0.48). Intervention patients were more satisfied with their physicians (P = 0.02) and primary care visit (P = 0.02), but had more all-cause hospitalizations at 6 months (1.5 vs. 0.7 hospitalizations, P = 0.0002) and 12 months (2.3 vs. 1.7 hospitalizations, P = 0.05). CONCLUSION: Adding symptom information to computer-generated care suggestions for patients with heart failure did not affect physician treatment decisions or improve patient outcomes.

Risk factors for nonelective hospitalization in frail and older adult, inner-city outpatients.

PURPOSE: In our study, we sought to improve the accuracy of predicting the risk of hospitalization and to identify older, inner-city patients who could be targeted for preventive interventions. DESIGN AND METHODS: Participants (56% were African American) in a randomized trial were from a primary care practice and included 1,041 patients living in the inner city who were either > or = 75 years of age or were > or = 50 years of age with severe disease. As a secondary analysis, we assessed patient characteristics at baseline involving five domains of health, including utilization and satisfaction. We followed participants for 12 months and recorded the occurrence of nonelective hospitalization within the study period. We developed a multivariate model using logistic regression to predict this outcome. RESULTS: The following patient characteristics independently predicted an increased risk for nonelective hospitalization: having the diagnosis of congestive heart failure, diabetes mellitus, or anemia; and having more medications prescribed, having a lower body mass index, and having more emergency department visits during the previous year. Better physical functioning reduced the risk of hospitalization. IMPLICATIONS: Moderate accuracy of a prediction model (0.73) was observed. In addition to focusing on patients with chronic disease, helping them maintain physical functioning may help reduce nonelective hospitalization.

Effects of computerized guidelines for managing heart disease in primary care.

BACKGROUND: Electronic information systems have been proposed as one means to reduce medical errors of commission (doing the wrong thing) and omission (not providing indicated care). OBJECTIVE: To assess the effects of computer-based cardiac care suggestions. DESIGN: A randomized, controlled trial targeting primary care physicians and pharmacists. SUBJECTS: A total of 706 outpatients with heart failure and/or ischemic heart disease. INTERVENTIONS: Evidence-based cardiac care suggestions, approved by a panel of local cardiologists and general internists, were displayed to physicians and pharmacists as they cared for enrolled patients. MEASUREMENTS: Adherence with the care suggestions, generic and condition-specific quality of life, acute exacerbations of their cardiac disease, medication compliance, health care costs, satisfaction with care, and physicians' attitudes toward guidelines. RESULTS: Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions. The intervention had no effect on physicians' adherence to the care suggestions (23% for intervention patients vs 22% for controls). There were no intervention-control differences in quality of life, medication compliance, health care utilization, costs, or satisfaction with care. Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients. CONCLUSIONS: Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease. Future studies must weigh the benefits and costs of different (and perhaps more Draconian) methods of affecting clinician behavior.

Structure, functions, and activities of a research support informatics section.

The authors describe a research group that supports the needs of investigators seeking data from an electronic medical record system. Since its creation in 1972, the Regenstrief Medical Records System has captured and stored more than 350 million discrete coded observations on two million patients. This repository has become a central data source for prospective and retrospective research. It is accessed by six data analysts--working closely with the institutional review board--who provide investigators with timely and accurate data while protecting patient and provider privacy and confidentiality. From January 1, 1999, to July 31, 2002, data analysts tracked their activities involving 47,559 hours of work predominantly for physicians (54%). While data retrieval (36%) and analysis (25%) were primary activities, data analysts also actively collaborated with researchers. Primary objectives of data provided to investigators were to address disease-specific (35.4%) and drug-related (12.2%) questions, support guideline implementation (13.1%), and probe various aspects of clinical epidemiology (5.7%). Outcomes of these endeavors included 117 grants (including 300,000 US dollars per year salary support for data analysts) and 139 papers in peer-reviewed journals by investigators who rated the support provided by data analysts as extremely valuable.

Installing and implementing a computer-based patient record system in sub-Saharan Africa: the Mosoriot Medical Record System.

The authors implemented an electronic medical record system in a rural Kenyan health center. Visit data are recorded on a paper encounter form, eliminating duplicate documentation in multiple clinic logbooks. Data are entered into an MS-Access database supported by redundant power systems. The system was initiated in February 2001, and 10,000 visit records were entered for 6,190 patients in six months. The authors present a summary of the clinics visited, diagnoses made, drugs prescribed, and tests performed. After system implementation, patient visits were 22% shorter. They spent 58% less time with providers (p < 0.001) and 38% less time waiting (p = 0.06). Clinic personnel spent 50% less time interacting with patients, two thirds less time interacting with each other, and more time in personal activities. This simple electronic medical record system has bridged the "digital divide." Financial and technical sustainability by Kenyans will be key to its future use and development.