The quality of harms reporting in journal publications is often poor, which can impede the risk-benefit interpretation of a clinical trial. Clinical study reports can provide more reliable, complete, and informative data on harms compared to the corresponding journal publication. This case study compares the quality and quantity of harms data reported in journal publications and clinical study reports of orlistat trials.Publications related to clinical trials of orlistat were identified through comprehensive literature searches. A request was made to Roche  for clinical study reports related to the orlistat trials identified in our search. We compared adverse events, serious adverse events, and the reporting of 15 harms criteria in both document types and compared meta-analytic results using data from the clinical study reports against the journal publications.Five journal publications with matching clinical study reports were available for five independent clinical trials. Journal publications did not always report the complete list of identified adverse events and serious adverse events. We found some differences in the magnitude of the pooled risk difference between both document types with a statistically significant risk difference for three adverse events and two serious adverse events using data reported in the clinical study reports; these events were of mild intensity and unrelated to the orlistat. The CONSORT harms reporting criteria were often satisfied in the methods section of the clinical study reports , but both document types satisfied 80–100 % of the results section criteria, albeit with greater detail being provided in the clinical study reports.In this case study, journal publications provided insufficient information on harms outcomes of clinical trials and did not specify that a subset of harms data were being presented. Clinical study reports often present data on harms, including serious adverse events, which are not reported or mentioned in the journal publications. Therefore, clinical study reports could support a more complete, accurate, and reliable investigation, and researchers undertaking evidence synthesis of harm outcomes should not rely only on incomplete published data that are presented in the journal publications.The online version of this article (doi:10.1186/s13063-016-1327-z) contains supplementary material, which is available to authorized users. There are two driving concerns that continue to grow when relying on published medical research to reflect the truth . First, Journal publications and registry reports currently represent the main information source for obtaining summaries of clinical trial data for the purposes of clinical and health policy decision-making . ResultsThe clinical study report (CSR) is a structured document that summarises the analysis methods and results of a clinical trial submitted for marketing authorization of an investigational medicinal product in the European Union, Japan, or the United States. CSRs are an ‘integrated’ full report, which can be up to a thousand pages in length, and include extensive detailed information on the efficacy and harms of interventions. The information in these documents relating to harms is usually separated individually by adverse event (AE) and serious adverse event (SAE) terms in summary tables and listings.In the past, researchers have made major efforts to gain access to CSRs, with the intention to inform regulatory decision-making . The infOrlistat  is marketed by Roche in most countries. It is used in the treatment of obesity as a selective inhibitor of gastric and pancreatic lipase . Mild, bWe aim to carry out an exploratory review consisting of two main analyses: (1) to compare the number(s) of reported harms (AEs and SAEs) and (2) the structured reporting of harms. Both analyses will be assessed between CSRs and journal publications using a case study of Roche-sponsored orlistat trials to provide a summary of the added value, if any, from the CSRs. To our knowledge, an in-depth exploration that includes a detailed meta-analysis of this type has not been published in previous CSR-related research.We planned to identify independent trials, each of which were reported within two different trial summary reports: CSRs and publically available journal publications. The aim was to compare these document types and determine whether there were inconsistencies in the quality and quantity of reporting of harms. The CSRs were released by Roche .A search was implemented by one researcher (AH) in the Cochrane Central register  and Ovid MEDLINE  to obtain all relevant published, randomised, controlled trials comparing orlistat against a placebo for obesity treatment. The search strategies are provided in Additional file Module I: The ‘Core report’ – background and rationale, objectives, materials and methods, efficacy results, safety results, discussion, conclusion and appendicesModule II: ‘Study documents’ – protocol and amendment history, blank case report forms (CRFs), subject information sheet and consent form, glossaries of original and preferred terms, randomization list, reporting analysis plan (RAP), certificates of analysis, list of investigators and list of ethics committee membersModule III: ‘Listings of demographic and efficacy data’Module IV: ‘Listing of safety data’Module V: ‘Statistical report and appendices’ – statistical analysis and efficacy resultsRoche was contacted and asked to provide the corresponding CSRs for each of the publications identified. A Roche CSR consists of the following five modules of information:Content and characteristics of both document types, including whether a clear primary objective of safety was defined, a word count of the information relating to harms in both the journal publication  and in the CSR documents of text only (word count performed using the software AnyCount version 7.0 ). MissinName of each reported AE and SAE term recorded for both placebo and orlistat, with the overall number of patients in the safety population, as defined in the respective document. The intensity grading , relationship to orlistat, and definition of the SAEs were also observed where possible. SAEs were defined as any event that was fatal or life-threatening, requiring hospitalization or prolongation of hospitalization, or an overdose. The AE coding system was also detailed.Reporting structure of harms , the following data were extracted:One researcher (AH) extracted, and a second reviewer (CTS) checked the data extraction. Discrepancies in the rates of agreement were resolved through consensus or recourse to a third reviewer (CG), where necessary. As there were no disagreements in the data extraction for the first three trials , extraction for the final two trials was only carried out by one reviewer (AH).For a particular trial, all harms (AEs and SAEs) reported in either the journal publication or the CSR were extracted and compared across the two document types. The clinically validated medical terminology dictionary MedDRA is commonly used during the regulatory process by all stakeholders in healthcare; it is used for coding harm outcomes. These reported outcomes were then organized into each of the five levels of the MedDRA dictionary: the system organ class, high-level group term, high-level term, preferred term, and lowest level term. Outcomes are usually reported in the journal publications and CSRs as MedDRA preferred term level events. Therefore, we compared the total number of reported MedDRA preferred terms, and if a preferred term was reported in both the CSR and journal publication, the numerical data were compared, and any discrepancies, noted.2 statistic [For each MedDRA preferred term (AE and SAE), the data extracted from the CSRs were used to estimate risk differences, which were pooled across trials using fixed-effect meta-analysis. A corresponding meta-analysis was performed using the data extracted from the journal publications wherever relevant. The pooled risk difference (RD) with 95 % confidence interval  and the tatistic  were comBOTH – both documents report the criteriaCSR – only reported criteria in the clinical study reportPub – only reported criteria in the trial publicationNR – criteria not reported in either documentUsing the CONSORT-harms extension  as a benThe total number of criteria satisfied in each CSR and journal publication for a particular trial was calculated and expressed as a percentage of 15 criteria.CSR (+) – The CSR provides more information than the journal publicationSimilar (O) – Both document types provide equal and similar informationCSR (-) – The journal publication provides more information than the CSRWhen both document types reported on any particular individual criteria (i.e. BOTH), the reported information was compared and classified as follows:Thirty-one journal publications related to 31 randomised controlled trials of orlistat were identified in our search  1,894), with an average of 10 % of words (mean (sd) 757 (287)) dedicated to safety. The CSRs had a mean (sd) of 163,411  words across all trials, with approximately 3 % (mean (sd) 4,663 ) related to safety. The mean difference between the CSR and journal publication was 3,906 ) words.MedDRA version 2.3 had been used to code AEs and SAEs in all five trials.The total number of MedDRA preferred terms for AEs varied across trials Fig.  Forest . The jouIn the meta-analysis (MA) for the AEs Table , 61 indiThe total number of MedDRA preferred terms for SAEs were generally poorly reported in journal publications Fig. . For theIn trial NM16189, 19 SAE terms were reported across the CSR and journal publication. Thirteen of these were reported in both documents, either with full numerical agreement (12 SAE terms) or with disagreement in numerical results  . Both the CSRs and the journal publications satisfied 80–100 % of criteria in their results sections, but greater detail was generally provided in the CSR. This included full summary tables of the AE and SAE data, including withdrawals due to harm, severity grading, and denominators for the numbers included in the safety population.This case study has shown differences in the completeness and quality of reporting harms-related information between journal publications and CSRs for five orlistat trials. Information on the patient-relevant harm outcomes, including SAEs, which is required for unbiased trial evaluation, was missing from the publicly available journal article. Including these missing data from the CSRs altered the magnitude of the pooled risk difference estimates in a few cases and even resulted in five statistically significant differences (including three AEs and two SAEs). The statistically significant risk differences for AEs were faeces discolouration, dry skin, and haemorrhoids, and for SAEs, carotid artery stenosis and varicose veins. However, the statistical significance of these SAEs could not be confirmed in a sensitivity analysis pooling relative risks , 28 due The quality of reporting between journal publications and CSRs showed inconsistencies when assessed by the CONSORT-harms reporting criteria. At 70–90 %, the methods section criteria were more often satisfied in the CSRs, compared to only 10–50 % of the criteria in the journal publications. However, both document types satisfied 80–100 % of the results section criteria, albeit with greater detail being provided in the CSR. The journal publication was often incomplete when reporting planned analyses and summary tables of AEs and SAEs, which were missing information on withdrawals, severity grading, and numbers in the safety population. Journal publications are often impeded by word count restrictions. However, inadequate reporting of harms is still noticeable, even after the release of the CONSORT-harms extension , as the In a recent study , findingThe drive to make clinical trial data more accessible has garnered widespread international support, with funders, academics, pharmaceutical industry, publishers and regulators supporting the move towards greater transparency. For example, the BMJ recently stated that it will no longer publish trials of drugs or devices where the authors do not commit to making the relevant anonymised patient-level data available; this was to be extended to all submitted clinical trials beginning 1 July 2015. In addition, the EMA has now adopted their new policy, making clinical trials data more accessible , includiOur study has a number of limitations. First of all, the meta-analysis results do not provide comprehensive unbiased clinical results, as they are based only on a subset of the five eligible orlistat trials, due to the inability to obtain CSRs for the remaining 26 identified trials, which were not Roche sponsored or pre-dated Roche’s policy (dating back to 1 January 1999). The meta-analyses were conducted without any adjustment for multiplicity, meaning that there is an increased chance of a false positive result, and the results should be interpreted with caution. In addition, for the five CSRs obtained from Roche in this study, some of the reports failed to include any information from modules II, III, IV, and V, and some had missing pages. Individual participant-level data and potentially other important information on harms are often presented in Roche’s CSR modules III-V. Access to these modules and confidential patient listings may have been restricted due to privacy violations, and these missing sections could present a possible cause of bias in the results. In a recent study , revieweThis case study confirms that CSRs can provide more complete and robust information on harms data collected in clinical trials, compared to publically available journal publications. CSRs often provide extensive information about the study methods, including design, conduct, and analysis of the trial. On the other hand, these reports are able to supplement journal publications to help facilitate the assessment of risk of bias in evidence synthesis of harm outcomes. Consequently, restricting an evidence synthesis to journal publications could have implications to systematic reviewers and other stakeholders involved in healthcare research when reaching reliable conclusions about the harmful effects of medical interventions.


State health departments in Michigan, Minnesota, Oregon, and Utah explored the use of genomic information, including family health history, in chronic disease prevention programs. To support these explorations, the Office of Public Health Genomics at the Centers for Disease Control and Prevention provided cooperative agreement funds from 2003 through 2008. The 4 states’ chronic disease programs identified advocates, formed partnerships, and assessed public data; they integrated genomics into existing state plans for genetics and chronic disease prevention; they developed projects focused on prevention of asthma, cancer, cardiovascular disease, diabetes, and other chronic conditions; and they created educational curricula and materials for health workers, policymakers, and the public. Each state’s program was different because of the need to adapt to existing culture, infrastructure, and resources, yet all were able to enhance their chronic disease prevention programs with the use of family health history, a low-tech “genomic tool.” Additional states are drawing on the experience of these 4 states to develop their own approaches. The Human Genome Project concluded in 2003, attracting attention to genomic research as a source for health information and applications . State pTo explore the potential use of genomic information in chronic disease prevention, the Centers for Disease Control and Prevention supported pilot programs in 4 states from 2003 through 2008. We describe the strategies, successes, challenges, and consequences of these programs, which offer potential models for using genomic information — particularly family health history — for public health action.The Chronic Disease Directors’ Summit in 2002 called on CDC to help states respond to knowledge and applications emerging from the Human Genome Project . In 2003Develop or expand leadership capacity in public health genomics.Develop and implement population-based assessments and incorporate genomics into disease-specific data collection through surveillance and registries.Implement or expand the use of genomics in program activities.Educate the health care workforce, policy makers, and the public about the importance and role of family health history and genetic risk factors in disease etiology and prevention.Prepare the chronic disease workforce for using genomic tools to reduce the burden of specific diseases, and teach them the benefits and limitations of genetic tests.From 2003 through 2008, four states — Michigan, Minnesota, Oregon, and Utah — received cooperative agreement funds for public health genomics. Annual awards between $150,000 and $250,000 allowed each state to support 1 full-time staff member. Additional staff were hired part-time or as student interns; health departments also contributed staff time in kind . States submitted annual progress reports to CDC.Michigan, Oregon, and Utah chose to expand their existing state genetics plans, developed in 2002 with support from the Health Resources and Services Administration. They enhanced these plans with specific goals and activities that emphasized the role of genomics in chronic disease prevention programs –7. For eAll 4 states integrated genomic information — particularly family health history — into prevention plans for 1 or more chronic diseases, including asthma, obesity and diabetes, heart disease, and stroke. The most detailed plans focused on cancer. Oregon’s comprehensive cancer control plan added an objective to increase awareness of cancer family history as a factor in individual cancer risk . MinnesoSome key accomplishments are summarized in the following sections, corresponding with the categories in Project staff in the 4 funded states identified “champions,” leaders within the health department who helped to develop partnerships and advisory groups. These groups varied in composition and scope, with members coming from various types of organizations: government agencies, academic and research institutions, health care plans, community groups, private businesses, genealogy organizations, and other entities. Oregon convened a broad Genetic Advisory Committee with clinical, public health, and academic members to gather input for Oregon’s Strategic Plan for Genetics and Public Health . MichigaAll 4 states had access to population-based data collected by state surveillance systems. Michigan, Oregon, and Utah added state-specific questions to the BRFSS , the state’s cancer registry, to assess completeness of cancer family history in oncology patients’ charts. They found that more than 80% of 853 charts documented the presence or absence of a family history of cancer and the tumor site; however, fewer than 10% included age at cancer diagnosis, a key indicator for assessing potential genetic risk . On the Michigan also developed a novel, population-based surveillance system for sudden cardiac death among the young (SCDY). Michigan used these data to bring attention to SCDY as a public health problem, identifying an underlying genetic cause in a large proportion of cases ,23.State programs used population-based data to inform educational activities, policies, and standards for using family health history to enhance early disease detection and prevention . MichigaMichigan integrated family history questions into the baseline participant survey of its Healthy Homes University program. This program is funded by the US Department of Housing and Urban Development (DHUD) to reduce asthma triggers in low- to moderate-income households that include a child with asthma. Sixty-five percent of children with diagnosed asthma in Michigan’s survey had at least 1 first-degree relative with asthma. By identifying affected relatives, Michigan’s program was able to offer education and products to reduce asthma triggers to 150 additional persons with asthma in 92 of the first 162 households enrolled in the project . This inFrom 2006 through 2009, the Michigan Colorectal Cancer Screening Program offered colorectal cancer screening to asymptomatic low-income, uninsured, and underinsured persons in 3 counties with high colorectal cancer mortality rates. The program linked local health departments with genetics services and provided data for use in communicating with program participants. Of the approximately 1,500 adults screened, 177 were referred to a genetic counselor. In Minnesota, the Department of Health integrated family history educational materials into the Sage Screening Program for breast and cervical cancer among underserved women aged 40 or older .BRCA1 or BRCA2 mutation in patients without cancer who met US Task Force on Preventive Services guidelines as well as genetic testing for Lynch syndrome according to National Comprehensive Cancer Network guidelines. The Oregon public health genomics program analyzed state legislation, drafted testimony, and provided information on legislative issues, such as the development of an Oregon Birth Defects Registry, the disclosures permitted by the Oregon Genetic Privacy Act, and the use of genetic information in criminal cases  conducting population-based assessments and surveillance to develop evidence for the use of genomic information and family history in state disease prevention efforts; 2) demonstrating the integration of this information into existing disease prevention programs, such as WISEWOMAN and Healthy Homes University; and 3) developing, disseminating, and documenting the uptake of educational materials for the health workforce, policy makers, and the public.The pilot programs also delivered some useful lessons on strategies and challenges for integrating genomics into public health programs for chronic disease prevention  31). Pe. Pe31). Successful strategiesObtain support of health department leadership and decision makers.Seek partnership with early adopters of genomics among disease prevention programs.Meet programs at their level of interest in a way that is flexible, responsive, and open to ideas.Engage local public health departments; they are an important setting for integrating genomic information into practice.Develop external partnerships; consider nontraditional partners, such as genealogists, private businesses, community members, information technology experts, pharmaceutical companies, and the news media.Develop communications and educational materials that are easy to understand, practical, relevant, and accessible to their intended audiences.Focus on activities that are relevant to existing programs, require only incremental changes, demonstrate value and impact, and are likely to be sustained.ChallengesEvidence-based guidelines and professional standards for integrating family health history, genetic testing, and genetic risk factors into disease prevention programs are limited.Disease prevention programs have many competing priorities and are reluctant to integrate genomics into their activities without a mandate from their funding source.Minimal financial support for public health genomics is available from state health departments and federal agencies.Cooperative agreements that exclude research and clinical services limit the ability of health departments to advance the field of public health genomics.Funds are limited or lacking to cover clinical genetic services and testing for persons who are uninsured, underinsured, or insured through Medicaid.No model or best practices exist for the organizational structure of state public health genomics programs.Most health departments have few staff members with training in genetics.Lack of a common vocabulary and other barriers hinder communication between public health practitioners and genetics experts.BRCA1 or BRCA2 or Lynch syndrome by the end of 2012. The Michigan Public Health Genomics Program and the MCSP established a bidirectional reporting system, which returns information on persons with characteristics suggesting hereditary cancer to the 150 health care institutions that report to the MCSP , Lynch syndrome, or familial hypercholesterolemia; most people with these conditions are not aware they have them, yet early detection and intervention could save their lives (The experiences of Michigan, Minnesota, Oregon, and Utah are useful to a growing number of states — including Connecticut, Ohio, and Georgia — that are developing their own approaches –36. Expeir lives .CDC’s Office of Public Health Genomics website offers materials for implementing interventions that proceed from evidence-based recommendations . Many of


Program areas that were generally working well in malaria in pregnancy programs (MIP) included: (1) integration of MIP interventions into antenatal care; (2) development of up-to-date policies; (3) active involvement of communities; and (4) development of capacity-building materials for training. Challenges remain in the areas of: (1) commodities; (2) quality assurance; (3) monitoring and evaluation; and (4) financing. Program areas that were generally working well in malaria in pregnancy programs (MIP) included: (1) integration of MIP interventions into antenatal care; (2) development of up-to-date policies; (3) active involvement of communities; and (4) development of capacity-building materials for training. Challenges remain in the areas of: (1) commodities; (2) quality assurance; (3) monitoring and evaluation; and (4) financing. Pregnant women and infants are particularly vulnerable to malaria. National malaria in pregnancy (MIP) programs in Malawi, Senegal, and Zambia were reviewed to identify promising strategies that have helped these countries achieve relatively high coverage of MIP interventions as well as ongoing challenges that have inhibited further progress.We used a systematic case study methodology to assess health system strengths and challenges in the 3 countries, including desk reviews of available reports and literature and key informant interviews with national stakeholders. Data were collected between 2009 and 2011 and analyzed across 8 MIP health systems components: (1) integration of programs and services, (2) policy, (3) commodities, (4) quality assurance, (5) capacity building, (6) community involvement, (7) monitoring and evaluation, and (8) financing. Within each program area, we ranked degree of scale up across 4 stages and synthesized the findings in a MIP table of analysis to reveal common themes related to better practices, remaining bottlenecks, and opportunities to accelerate MIP coverage, strengthen MIP programs, and improve results.Each of the 3 countries has malaria policies in place that reflect current MIP guidance from the World Health Organization. The 3 countries successfully integrated MIP interventions into a platform of antenatal care services, but coordination at the national level was disjointed. All 3 countries recognized the importance of having a MIP focal person to ensure collaboration and planning at the national level, but only Malawi had appointed one. Commodity stockouts were frequent due to problems at all levels of the logistics system, from quantification to distribution. Lack of support for quality assurance and weak monitoring and evaluation mechanisms across all 3 countries affected optimal coverage.MIP programs should address all 8 interconnected MIP health systems areas holistically, in the context of a health systems approach to building successful programs. The MIP table of analysis can be a useful tool for other malaria-endemic countries to review their programs and improve MIP outcomes. Malaria in pregnancy (MIP) contributes to maternal anemia, maternal death, stillbirth, spontaneous abortion, and low birth weight.Regional Office for Africa developed a framework to prevent and control malaria during pregnancy. The framework promotes a 3-pronged approach in stable malaria transmission areasIn 2004, the World Health Organization (WHO) Intermittent preventive treatment of pregnant women (IPTp) with the antimalarial drug sulfadoxine-pyrimethamine (SP)Use of insecticide-treated bed nets (ITNs)Effective case management among pregnant women showing signs and symptoms of malariaReflecting the latest evidence that frequent dosing of IPTp-SP is effective in reducing the consequences of MIP,The first IPTp-SP dose should be administered as early as possible during the second trimester of gestation.Each SP dose should be given at least 1 month apart.The last dose of IPTp-SP can be administered up to the time of delivery without safety concerns.,The global health community has committed to achieving at least 85% coverage of intermittent preventive treatment of pregnant women with antimalarial drugs.At the 2000 African Summit on Malaria held in Abuja, Nigeria, 44 African nations committed to the goal that 60% of pregnant women at risk of malaria would be covered with the above MIP interventions by 2005.P. falciparum, have revised national policies and supported MIP programs in line with WHO's 3-pronged approach. However, many countries are far from achieving their targets for both IPTp uptake and ITN use. Van Eijk et al. found 45 of 47 countries surveyed (96%) had a policy for distribution of ITNs for pregnant women; 39 of 47 countries (83%) had an IPTp policy; in 2007, an estimated 6.4 million of 25.6 million pregnant women (25%) received at least 1 treatment dose and 19.8 million (77%) visited an antenatal clinic (31 countries). Estimated coverage was lowest in areas of high-intensity transmission of malaria.In the last decade, 39 African countries,Hill et al. systematically examined both demand and supply factors associated with low coverage of IPTp uptake and ITN use. In some countries, they found poorer women, women with no education, and women living in rural areas were significantly less likely to have IPTp coverage or an ITN. Also, not surprisingly, women's pattern of ANC use was a more important determinant of IPTp uptake than for ITN ownership. ANC use was affected by provider performance, organizational problems at the facility, health system weaknesses beyond ANC, and factors that cannot be controlled by the health system, such as pregnant women delaying ANC attendance.In light of most countries' suboptimal progress, we conducted MIP case studies in Malawi (2011),In addition to being PMI focus countries, these 3 countries were selected because, although they have not achieved target MIP goals, they have been more successful than other sub-Saharan African nations in increasing IPTp uptake and, to some extent, ITN use. Using a positive deviance approach,,MIP is a core component of focused antenatal care (FANC) services.Country MIP policies that are based on the latest scientific evidence and include defined goals as well as national guidelines to achieve those goals set the stage for effective MIP implementation. Policies need to be harmonized and effectively integrated across different divisions of the health sector as described under “integration.”Commodities include not only correct medicines and medical products but also having systems in place to ensure availability of commodities at the point of service. For MIP, this includes availability of SP, cups and water for IPTp, and long-lasting ITNs at ANC. It also includes diagnostic tools, rapid diagnostic tests and/or microscopy, and treatment medicines to effectively provide case management to pregnant women with signs of malaria.Quality assurance is a wide-ranging concept covering all matters that individually or collectively influence the efficacy, safety, appropriateness, and acceptability of services. For MIP, this includes performance standards to measure quality of care, supervision support to improve the quality of care, and self-assessment by health care providers to monitor their own delivery of services.Capacity building is defined as strengthening human resources by improving knowledge and skills. For MIP, this includes competency-based preservice and in-service training that reflects current WHO guidance and national policies.Community engagement is defined as the involvement of communities in the promotion and/or delivery of health services. For MIP, this includes raising awareness about MIP prevention and control; for example, early attendance at ANC, promotion of IPTp and ITNs, and effective case management. Availability of resources and effective monitoring of health promotion are key components of this program element.Monitoring and evaluation, when effective, will capture MIP service delivery indicators correctly and will, on a regular basis, feed into a national health management information system. These data will be used for decision-making at all points of care and at the national level for policy formulation. National-level surveys to evaluate the coverage and health impact of MIP programs are a critical component of programs to help understand trends in health outcomes and drive program decision-making.Financing includes a combination of national government and donor funding that guarantees MIP programs receive the support and resources they need to consistently reach all pregnant women.The specific case study objectives were to identify:Promising practices/strategies that have supported MIP programming successExisting bottlenecks in MIP program implementation and how these are addressedLessons learned that can inform future MIP programming in other countriesWe used a systematic case study research methodology to analyze the factors contributing to successes in national MIP programs in Malawi, Senegal, and Zambia, based on the 8 health system areas, as well as challenges that have hindered further progress. This type of research is well-suited for exploring complex issues in depth, such as health systems functioning, and can help illuminate findings from previous quantitative research, such as household and facility surveys.Data collection methods in each country consisted of a comprehensive desk review of the literature and secondary data, followed by qualitative key informant interviews with national MIP stakeholders, including representatives from the National Malaria Control Programme (NMCP), National Reproductive Health Programme (NRHP), staff from the U.S. Agency for International Development (USAID) and PMI, and implementing organizations supporting the Ministry of Health. Key informants were selected using both purposive and snowball sampling techniques.For the desk review, we identified such documents as national policies and guidelines—for both malaria and reproductive health, where comprehensive ANC services, including MIP, are provided to pregnant women—as well as national progress reports and assessments. We also reviewed applications and progress reports for the Global Fund to Fight AIDS, Tuberculosis and Malaria , PMI Malaria Operational Plans, peer-reviewed articles, implementing partner reports, national health management information system (HMIS) reports and forms, as well as Demographic and Health Surveys and Malaria Indicator Surveys.Information from the initial desk review was used to identify gaps in program-related MIP information and areas requiring further elucidation. This informed the development of qualitative key informant interview guides with input from stakeholders from the NMCP and the NRHP. A set of questions, linking back to the 8 health system areas of MIP, was developed for the first country (Zambia). The questions were not pilot tested but were refined for use in subsequent countries, adapting them to the country context and to the specific stakeholder's area of MIP support and job function. For example, key informants from organizations supporting logistics management were primarily asked questions related to procurement and distribution of MIP commodities.Data were collected in Zambia from September 2009 to October 2009; in Senegal, in March 2010; and in Malawi, in January 2011. The length of the interviews ranged from approximately 60 minutes to 90 minutes, and information from respondents was recorded on paper questionnaires and then transcribed on the same day into a Microsoft Word document. When information was unclear or information from stakeholders was conflicting, the interviewees were given the opportunity to review the draft report and provide clarification.,Degree of scale up within each MIP program area was ranked on a scale of 1 (nothing to little had been done) to 4 .The study team conducted content analyses for the secondary and qualitative data for each country using the 8 MIP health system areas. Within each MIP program area, the study team determined degree of scale up by ranking progress made along 4 stages . A ratinFew differences in opinion among the study team were encountered in terms of how each health system area should be rated; however, when they did occur, discussions among researchers and authors of all 3 country case studies were held, using the MIP matrix as the guide to rate all countries and elements fairly. Information was coded and organized manually, and anonymous quotations were selected to illustrate key points while preserving participant privacy.–In this article, we synthesized the findings across the 3 MIP case studies conducted in Malawi,A total of 43 key informants were interviewed across the 3 countries , representing a diverse group of national stakeholders in each country involved in MIP service delivery. No one who was asked to participate refused, and no one ended their interview early.commodities, quality assurance, and financing accounted for the most significant challenges across countries, with scores generally ranging from 2.0 to 2.5 in these program areas. Each program area is described in more detail below.Problems with commodity stockouts, quality assurance, and financing accounted for the most significant MIP program challenges in the 3 countries.After the 2000 Abuja Summit, all 3 countries successfully brought together malaria control and reproductive health policy makers and program implementers, through malaria or MIP-specific working groups, to institute MIP policies and interventions. In line with WHO recommendations, the countries successfully integrated MIP interventions into a platform of ANC services at the facility level—a key step in reaching the current levels of coverage.Since this initial rollout, however, political will has waned or been diverted elsewhere, and while services at the facility level remain integrated, national-level coordination and planning has become disjointed. At the time of data collection, MIP working groups in Malawi and Zambia were reported to be dissolved or inactive, not due to a conscious decision of stakeholders but due to competing health priorities. The Malawi NMCP did, however, have a MIP focal point person on staff who reportedly intended to revitalize the link between the NMCP and the Reproductive Health Unit (RHU). Zambia had been seeking funding for a MIP focal point person but, at the time of this writing, had yet to succeed. In Zambia, a lack of human resources in the Ministry of Health was reported to be a major constraint in cross-sector coordination. The RHU and the NMCP confirmed that although representatives of the other unit are invited to participate in joint annual planning, mutual participation in the planning process has been minimal for the last several years because there are not enough staff to attend each other's meetings. This reportedly resulted in the shifting of MIP funds to other priority areas of malaria implementation.In Senegal, one interviewee noted:… national-level integration may be less effective because coordination of national activities is not routine … and the level of joint planning [between the NRHP and NMCP] is low.This lack of coordination negatively affects program components, including training capacity, supervision, and availability of commodities. In Malawi and Senegal, lack of coordination has resulted in parallel, duplicative MIP trainings, conducted independently by different groups for the same health care providers. At the time of this article, a focused antenatal care (FANC) working group had been created in Zambia to address issues in MIP programming; however, the group has struggled to accomplish tasks because the RHU, NMCP, and implementing partners have limited funding and staff to support MIP and FANC.All 3 countries have malaria policies in place that reflect WHO MIP guidance. In Senegal and Zambia, national reproductive health and malaria control policies and guidelines have been harmonized through strong leadership by the NMCPs and commitment from partners to support the process. Dissemination of national guidelines in both Senegal and Zambia has been widespread. In Zambia, specifically, the NMCP conducted case management updates to reorient providers, addressing issues such as the correct use of SP, and, at the time of data collection, planned to distribute revised treatment guidelines with a memorandum to district-level staff for dissemination to providers.In Malawi, there are inconsistencies between reproductive health and malaria guidelines. For example, the national reproductive health service delivery guidelines stipulate IPTp provision at defined week intervals, while the national malaria guidelines stipulate IPTp provision following quickening and giving at least 3 doses 1 month apart. The Malawi reproductive health guidelines also stipulate that providers should not administer SP after 36 weeks gestation, while the malaria guidelines note no such limitation. Providers may provide different care depending on which set of national guidelines they refer to. What providers actually practice in all 3 countries is unknown as documentation of findings during supervision visits was not available.Sulfadoxine-pyrimethamine: In each of the 3 countries, WHO-recommended medicines for malaria treatment for pregnant women and for IPTp are approved and available through ANC clinics. However, stockouts of SP at ANC clinics were frequent due to central-level stockouts and ineffective distribution systems. This problem was further exacerbated by the irrational use of SP (based on key informant interviews) to treat malaria cases in the general population, whereas SP should be reserved for preventing malaria in pregnant women. In Zambia, although NMCP partners routinely provided the Ministry of Health with early warnings of impending stockouts of SP, stockouts persisted. This happened in 2009, when one implementing partner had to shift US$50,000 meant for rapid diagnostic tests to procure an emergency stock of SP.Stockouts of antimalaria drugs and bed nets were frequent.One stakeholder interviewed in Zambia described the situation:Sometimes you go to a clinic and they are stocked out of SP and they say it is because there isn't any at the district. Then, you go to the district and find it. Sometimes, they are stocked out at the district, but you find it at the central level.In Malawi and Senegal, stakeholders described similar issues with persistent SP stockouts. Stakeholders cited problems at all levels of the logistics management system for commodities, including quantification, ordering of drugs in a timely manner, tendering, receipt, storage, and distribution.Insecticide-treated bed nets: In the 3 countries, distribution of nets to pregnant women free of charge at ANC clinics is considered an effective mechanism for increasing usage among pregnant women and for incentivizing ANC attendance. Nevertheless, as with SP, facilities often experienced ITN stockouts due to procurement shortfalls, central-level stockouts, and disjointed distribution systems.In Malawi, it was reported that ITNs were frequently, but not always, available in ANC clinics. Facility supplies were based on estimated target populations rather than consumption, but recent changes from a single- to a multi-distributor system led to increased stockouts. At the time of data collection, all 3 countries were planning to implement universal ITN coverage campaigns, aimed at increasing net usage by the general population, and supplemental efforts targeting pregnant women and children under 5 years of age.Quality assurance systems for MIP programs were not functioning in any of the 3 countries.Due to lack of funding and competing responsibilities among Ministry of Health staff, comprehensive quality assurance systems were not currently functioning in any of the 3 countries. While MIP clinical performance standards had been developed in each of the countries, application of these standards was inconsistent. In large part, each country relies on routine supervision from national, provincial, or district-level supervisors; however, due to lack of human resources and logistical and financial constraints, these visits were not consistently conducted. In 2006, Zambia developed an integrated reproductive health tool composed of reproductive health standards that included MIP . Provincial-level Ministry of Health staff were oriented to this tool with the intention that training would cascade down to district- and facility-level staff. At the time of data collection, it was unknown if district-level orientations had been completed and, according to stakeholder reports, the tool was not in widespread use.Although Malawi has designed an integrated tool for quarterly supervision visits that targets infection prevention, MIP, reproductive health, and prevention of mother-to-child transmission of HIV, these visits were occurring infrequently. In Malawi, one interviewee mentioned:Donors place more emphasis on “number of persons trained” in program-reporting indicators than on the number supervised or the impact of training those persons, with program design following suit.In Senegal, the program review revealed that 31% of health facilities did not receive any kind of supervision.Lack of supervision has negative implications for consistent delivery of quality services for pregnant women as well as the general population. This can contribute to SP stockouts as well as to increased morbidity and mortality from improperly treated non-malarial fevers. For example, in Malawi and Zambia, stakeholders reported that SP was often used by providers to treat fevers in men, children, and non-pregnant women; in Zambia, SP was given when rapid diagnostic tests were negative; and in Malawi, SP was given when there were stockouts of artemisinin-based combination therapies (ACTs).Lack of coordination at the national level contributed to redundancies in training.Malawi, Senegal, and Zambia have all updated in-service training and preservice education materials with MIP content. This positions each country to focus training on evidence-based updates and maintenance of critical MIP competencies. However, as noted previously under the integration findings, at the time of data collection, there was a need to harmonize efforts further to avoid redundancies in training, both between preservice education and in-service training and within in-service training courses.In Malawi, the RHU and NMCP were implementing parallel in-service training events. As one interviewee pointed out:Where is the rocket science in MIP? We present focused ANC like it's something new, but it's the same thing [health care providers] have been doing.Human resource shortages are a major challenge in all 3 countries and affect access to quality of care. Zambia was 28,000 health professionals short of its Ministry of Health staffing targets. In Malawi, interviewed stakeholders said many providers were over-diagnosing malaria because of high client loads (implying not enough trained staff), lack of time or skills for proper clinical diagnosis, and the propensity for providers and clients alike to presume all fevers are malaria.All 3 countries were actively supporting community involvement to enhance and engender community education and mobilization. In Malawi, community groups  actively partnered with health facilities to raise awareness in communities about health issues, including MIP; to refer women to ANC; and to identify key health problems in the community.In Zambia, community groups  were trained to sensitize communities about a range of maternal health topics in order to promote healthy behaviors and improve care seeking, including for MIP. Although one program follow-up report noted increased ANC attendance in the year since the community program was implemented, no improvements were seen in IPTp coverage due to frequent SP stockouts and poor recordkeeping. At the time of data collection, support for community involvement was not consistent, and more strategies were required to adequately involve communities and foster links between communities and facilities in a sustainable way.Qualitative feedback suggests that community involvement helped to improve use of bed nets.Although there is little documentation and assessment of these community-focused efforts, qualitative feedback suggests they were effective. For example, in Senegal, stakeholders attributed improved ITN use among pregnant women to the USAID-supported “Community Action against Malaria and Tuberculosis” program and in Malawi, to community involvement.MIP indicators are generally tracked through a variety of sources in malaria-endemic countries, including: (1) periodic household surveys, such as Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and Malaria Indicator Surveys; (2) the routine national HMIS; and (3) sentinel site surveillance systems (now less common). In the 3 countries, health facilities routinely collected and reported data on IPTp uptake by dose during ANC services through the HMIS, which aggregates data into national coverage indicators. However, the WHO-recommended MIP indicators on “percentage of ANC staff trained in the control of MIP in the past 12 months” and “percentage of screened pregnant women with severe anemia in the third trimester, by gravidity”ITN indicators have been effectively integrated into the HMIS in Senegal but were absent from the HMIS in Malawi and Zambia. Instead, such information was collected on parallel, program-specific reporting forms. HMIS data quality in Malawi and Zambia was reported to be weak by key informants, but Zambia was making strides to train district medical offices and health facility staff in data management. Prior to data collection, Senegal had taken significant steps, including hiring of new staff and establishment of a web-based data management system, to improve data completeness, timeliness, and reliability.While SP stockouts were reported to be a significant inhibiting factor for MIP programs, data on stock levels were not routinely made available to reproductive health and malaria control stakeholders. Additionally, at the time of data collection, no countries were reporting national data on MIP incidence or treatment—crucial indicators for measuring the effectiveness of MIP interventions.All 3 national governments commit some funds to MIP programming but still rely heavily on donor support. The Senegalese and Zambian governments were providing funding for SP, with central-level shortages reportedly due more to poor quantification of necessary medicines than to lack of funding. For ITNs, the 3 countries relied entirely on donors, primarily the Global Fund and PMI, which has proved insufficient to cover all pregnant women. While the “Sector-Wide Approach”—a resource allocation system that pools all health sector resources from all sources and allocates funds based on need—had been effective in Malawi for coordinating donor support, lack of accountability of funds provided directly to the government limited contributions to the basket fund. Delays in receipt of Global Fund monies in Malawi and Zambia further hindered program implementation. Across sub-Saharan African countries, funding to support malaria programming has increased since 2004; however, the currently available funding is far below the estimated US$5.1 billion required each year to reach universal coverage of interventions. In 2012, the global total of international and domestic funding for malaria was US$2.5 billion—less than half of what is needed.MIP programs should consider all areas of the health system to improve MIP outcomes.Although each country's MIP programming experiences, situation, and needs are unique, Malawi, Senegal, and Zambia all had issues in the areas of commodities, quality assurance, and financing that, with attention, could contribute to improved coverage and MIP outcomes. Careful consideration should be given to addressing all health system areas—even areas that rank high—since the elements are interconnected, and weaknesses in one area can negatively impact other areas. This is especially true in the area of integration, which includes the critical partnership between national reproductive health and malaria control programs to coordinate, plan, and harmonize policies and support synchronized implementation.Even though the 3 countries studied were considered high-performing MIP countries, none had achieved full coverage of IPTp uptake and ITN use among pregnant women. This is not surprising given each country's low scores in the crucial aspects of financing and commodities. The case studies highlight important lessons learned in each of the 8 MIP program areas that other countries can apply to improve their programs.integration, lessons focus on strengthening or creating national technical working groups that include the NRHP, NMCP, and National AIDS Control Programme (NACP) to ensure harmonized policies, guidelines, and educational materials, as well as guarantee effective and coordinated (non-duplicative) implementation. A focal point person responsible for coordinating MIP programs across sectors can help ensure consistency and maintain political will.A focal point person for MIP programming can help maintain political will.In the area of policy component, the case studies demonstrated that MIP policy should not only be in line with WHO-recommended guidelines but also be interpreted and presented in a consistent manner across all MIP-relevant documents. The October 2012 updated WHO policy recommendation for IPTp-SP—recommending IPTp begin as early as possible in the second trimester and be given at each routine ANC visit at least 1 month apart thereafter—affords countries an excellent opportunity to reinvigorate their MIP programs and review and revise policies and service delivery guidelines. If led by the NRHP and properly coordinated with the NMCP, countries could attract the support—technical and financial—needed to harmonize and disseminate updated guidelines and ensure consistent delivery of MIP services.For the commodities include the value of well-circulated guidance and consistent supervision to ensure that SP is reserved only for pregnant women, thereby ensuring adequate commodities for IPTp and curtailing resistance due to SP misuse. Additionally, coordination of supply chain management and skills in quantification and distribution must be improved. Without consistent supplies of MIP commodities, all other program efforts to increase coverage of interventions will be rendered ineffective.Lessons about Quality assurance mechanisms that target onsite managers and providers with quality improvement tools that allow for self-assessment can alleviate the barrier of financial and human resource constraints. Self-assessment can further encourage health care providers to find local solutions to address performance gaps.Capacity building was most successful when it focused on both preservice education and in-service training so that health care providers enter the workforce with up-to-date knowledge and skills, and costly in-service trainings can be reserved for periodic updates on MIP guidelines. Strengthened preservice training and alternative in-service capacity-building strategies, such as on-the-job training and mentorship, could contribute to improved training but currently lack emphasis in national programs.Community involvement/engagement was a highly visible component of each country's program. While the programs focused primarily on traditional health messaging and communication to promote ANC attendance and use of ITNs and IPTp, there was also some evidence of efforts to link the community with facility-level care to support better delivery of commodities  and access to care. For community-level interventions to be successful and sustained, the communities they serve need to take ownership of their activities and responsibility for supporting them.monitoring and evaluation processes, MIP indicators related to IPTp and ITNs are being collected through routine and periodic mechanisms but not necessarily captured and aggregated through the HMIS. Since tracking of ITN provision during ANC was not integrated into the HMIS in 2 of the 3 countries, this created challenges for national synthesis and reporting. In addition, information on case management of MIP was lacking in all countries.In terms of Priority indicators must be integrated into the national health management information system.To improve MIP monitoring, including data quality and use, priority indicators related to WHO's 3 approaches to MIP prevention and control must be integrated into the national HMIS. District officers and providers must also be trained on data collection, aggregation, and use of data for decision-making, and routine monitoring support must be incorporated into supervision and quality assurance efforts.financing, although a problematic area, was not without solutions. Lessons learned included the importance of advocacy to build in-country awareness from the community to the national level for more dedicated support to MIP programming. By gradually increasing national budgetary inputs to MIP interventions, countries can combat donor fatigue and improve program sustainability.Finally, The Expanded MIP Table of Analysis used to synthesize the 3 country case studies can be adapted to the needs of other countries interested in assessing the status of their own MIP programs. Similar case studies have been conducted in Burkina Faso, India (Jharkhand State), and Rwanda to comprehensively review all technical aspects of their malaria program. This simple and straightforward matrix is a promising tool to help countries move their MIP programming forward and accelerate progress toward national scale up.The findings from the case studies have been disseminated through workshops in Malawi, Senegal, and Zambia. Following the dissemination workshop in Senegal, country stakeholders began using the recommendations to inform development of its 2012 Roll Back Malaria roadmap. Specifically, Senegal planned to accelerate free distribution of ITNs during ANC and to integrate reproductive health and malaria programs by developing a joint coordination committee, with a special focus on training and community-level interventions. In Zambia, a FANC technical working group was formed, with representation from the RHU, NMCP, and other relevant partners. This group is finalizing and moving forward an action plan of MIP program priorities, including introduction of the new WHO policy for IPTp.The country case studies were limited to secondary data gathered through the desk review process, as well as qualitative data collected through in-depth interviews among key stakeholders at the national level. Due to time and resource constraints, the country case studies did not generally include interviews with key stakeholders at the regional, district, or facility levels. In Malawi, one District Medical Director was interviewed. Hence, the case studies present a limited but comprehensive picture of MIP prevention and control programming at the national level. Also, since the case studies only targeted better-performing countries, it is not possible to compare the findings to lower-performing countries that could reveal new insights to existing challenges in MIP programming.Further, while the review is meant to focus on MIP comprehensively, the focus is primarily on IPTp uptake and ITN use and does not address case management in detail, because very little information about case management of pregnant women was found at the country level.This review is particularly important now following the release of the new WHO IPTp guidance as countries review and update national MIP policies. The timing affords countries the opportunity to reprioritize MIP programming and reinvigorate partnerships between reproductive health and malaria control programs, to ensure effective technical oversight and program management. As countries move forward with MIP program acceleration and scale up, it will be important to keep in mind the 3-pronged approach to MIP control, comprising IPTp uptake, ITN use, and case management. Addressing the 3 approaches across each of the interconnected health system areas for MIP lends to a holistic approach to strengthening the health system and lasting results. With this in mind, countries should consider bolstering MIP case management—there is very little data or information to inform what is happening at the country level—as a core component of comprehensive MIP control. As malaria transmission patterns change from high to low, case management of pregnant women will increasingly become more important. The findings from this review as well as the country application of the Expanded MIP Table of Analysis are important tools for countries to review and apply to continue increasing coverage and improving MIP outcomes, and for moving MIP from neglect to priority.


In hydroelectric dominated systems, the value and benefits of energy are higher during extended dry periods and lower during extended or extreme wet periods. By accounting for regional and temporal differences in the relationship between wind speed and reservoir inflow behavior during wind farm site selection, the benefits of energy diversification can be maximized. The goal of this work was to help maximize the value of wind power by quantifying the long-term (30-year) relationships between wind speed and streamflow behavior, using British Columbia (BC) and the Pacific Northwest (PNW) as a case study. Clean energy and self-sufficiency policies in British BC make the benefits of increased generation during low streamflow periods particularly large. Wind density (WD) estimates from a height of 10m  were correlated with cumulative usable inflows (CUI) for BC (collected from BC Hydro) for 1979–2010. The strongest WD-CUI correlations were found along the US coast (r ~0.55), whereas generally weaker correlations were found in northern regions, with negative correlations (r ~ -0.25) along BC’s North Coast. Furthermore, during the lowest inflow years, WD anomalies increased by up to 40% above average values for the North Coast. Seasonally, high flows during the spring freshet were coincident with widespread negative WD anomalies, with a similar but opposite pattern for low inflow winter months. These poorly or negatively correlated sites could have a moderating influence on climate related variability in provincial electricity supply, by producing greater than average generation in low inflow years and reduced generation in wet years. Wind speed and WD trends were also analyzed for all NARR grid locations, which showed statistically significant positive trends for most of the PNW and the largest increases along the Pacific Coast. Global wind power generation is growing rapidly, with total investments of $99.5 billion and a record 49GW of newly installed capacity in 2014 alone [One of the most promising solutions to the issue of intermittency is energy storage in existing hydroelectric reservoirs –6. LargeMany studies have addressed the challenges of integrating wind and hydro power at the operational level, such as real-time voltage fluctuations and next-hour forecasting –11, and For example, wind farms with above-average generation during low inflow periods would have greater value than otherwise similar sites where most generation occurs during periods of high inflows and reservoir levels when electricity prices are typically lower. Similarly, sites with below-normal generation during high inflow periods help to maintain system flexibility, thereby reducing the need to spill from overfilled reservoirs and pay wind farms to curtail production, as occurred in Washington State during the freshet of 2011 .Clean Energy Act (2010) [Clean Energy Act’s self-sufficiency requirement also requires that in-province generation be able to meet all domestic demand by 2016, based on an average water year. However, unlike many other hydroelectric dominated systems, BC is capacity limited under most conditions, making additional generation during periods of high demand more important, but reducing the utility of additional energy except during extended drought periods [The Canadian province of British Columbia (BC), and the broader Pacific Northwest (PNW) region, were chosen to explore the spatial variability of the 30-year co-variability in wind speeds and hydroelectric reservoir inflows and to identify regions with beneficial and detrimental wind speed timing. The potential benefits of wind and hydroelectric resources with poorly-correlated temporal behavior are particularly strong in BC, where hydropower accounts for 95% of all electricity generation  and the t (2010)  has requ periods .Given a projected 20% increase in BC population over the next two decades, energy forecasts for BC suggest a strong likelihood that energy demand will also increase . ContinuAs a case study, the PNW also has the advantage of including a wide geographical range that encompasses several climatic regions and spans an international border. The region includes coastal and inland sites, a large latitudinal range, and multiple mountain ranges. Long–term wind behavior is likely to differ between these regions, and a heterogeneous wind resource increases the likelihood that some areas will exhibit beneficial multi-decadal wind timing relative to hydroelectric inflows. The strong linkages between BC and west coast United States energy systems mean there are also implications for international energy trading and market prices, particularly for the large installed wind power capacity in Oregon and Washington States.Several wind speed studies have included or been conducted in the PNW, but the results have been inconsistent and their geographic extent in BC is very limited –36. GrifThe objectives of this study are three-fold. First, we use the North American Regional Reanalysis (NARR) data  to produAlthough the study area included a broad definition of the PNW (40° to 65°N and 110° to 135°W) to provide a more effective investigation of latitudinal and geographic patterns in wind behavior, the study focused on the province of British Columbia, the states of Washington and Oregon, and the nearshore regions where offshore wind farms would be feasible. The study area was separated into 7 distinct regions based on political boundaries, proximity to the coast, and the divide between northern and southern British Columbia . RegionaAll wind speed data were obtained from the North American Regional Reanalysis (NARR) dataset , produceReservoir inflow data for BC were obtained from BC Hydro in the form of monthly combined usable inflows  for 1979 to 2010, which were summed to produce seasonal and annual totals . CUI is For each NARR grid location in the study area, linear trends were calculated for monthly mean winds and WD totals. While the assumptions of ordinary least squares regression (OLS) are not likely to be met for climate trend analysis, due to the cyclic, autocorrelated nature and non-normal distribution of wind speed and wind density data ,40, OLS Three sets of analyses were performed to understand the interannual and seasonal relationships between WD and CUI. First, interannual correlations were calculated between annual WD and CUI totals for each NARR grid location using Pearson correlation coefficients. Although the assumption of a linear relationship is unlikely to be met, Pearson was chosen because other nonparametric tests, such as Spearman’s rank correlation, reduce the sensitivity to extreme values, which were our primary interest.Second, to determine whether WDs during the lowest inflow years were significantly different from those in other years, a non-parametric Mann-Whitney U (aka Rank Sum) test was used to compare WD totals for the lowest CUI years and WD totals in all remaining years. The two populations were considered distinct if the sum of the ranks of each population were statistically different (p < 0.1). This test was performed for the three and five lowest inflow years to test if the results were robust across low inflow years in general, or were rather a product of the particular years in question . The samFinally, to determine if wind density totals for the highest and lowest inflow seasons were statistically different from the rest of the year, the same analysis was performed for the winter (December-March) and freshet (May-July) seasons, testing the WD totals in those months against all remaining months of the year. Annual CUI and WD totals were based on the October through September water year, while seasonal analyses included the freshet period (May through July) when inflows are highest in the PNW, and winter (December through March) when inflows are lowest.The analysis of 10m NARR monthly average wind speeds showed significant positive trends (p < 0.1) for most of the PNW . HoweverThe inverse variance weighted mean trend was similar for most regions , howeverWind density trends exhibited a similar pattern to the monthly mean wind speeds, with large increases for most of the PNW . The strMean wind speed and density trends at BC’s existing and potential wind farm sites were all positive and larger than their respective regional averages, except for the South Coast where the regional average wind speed trend was larger . The larMost of the PNW exhibited non-significant (p > 0.1) positive correlations between annual CUI and WD totals . HoweverMost regions had at least one location with a negative WD-CUI correlation, but even the strongest negative correlations, located in the North Coast and Far North regions, were not significant, with minimum values as low as -0.281.All of the potential wind farm sites had similar WD-CUI correlations to their respective regional averages . The potWind density anomalies  varied substantially from region to region for the lowest inflow years . The NorThe other regions  contained sites with significant anomalies in the three lowest inflow years, but all exhibited substantially different behavior when considering the five lowest inflow years. The Far North had many weak negative anomalies in the three lowest inflow years, but no sites exhibited significant anomalies in the five-year case . Like thAnomaly magnitudes and geographic patterns of significance were similar for both the three and five year low inflow cases, but the number of locations with significant anomalies was much higher for the three lowest CUI years compared to the five lowest years for most regions. However, the US Interior had more than double the number of significant anomalies for the five lowest inflow years compared to the three lowest inflow years .Wind density anomalies for the highest inflow years were more homogeneous than for the lowest inflow years , with poWhen comparing the three and five-year high inflow cases, the locations with significant wind density anomalies for the five highest years were shifted slightly southward when compared with those for the three highest years. The number of sites with significant anomalies in the five-year case declined for the North Coast and Northern Interior, but increased for all other regions . Many ofAlmost all sites exhibited significant WD anomalies in the winter and freshet seasons , compareFor most regions the NARR wind speed trends  were incThe increasing wind speeds at mid- and high-latitudes seen in the NARR data are consistent with many of the predicted effects of recent climate warming. Studies have suggested that the zone of tropical convection has been widening in recent decades , which hIf the positive wind speed and wind density trends observed here continue, this would bode well for the potential of wind energy in BC and the PNW. In particular, there is already one industrial scale wind power development, and many proposed sites, along BC’s Pacific Coast where the largest positive trends were observed. However, this result represents a historical analysis covering only 30 years, which may not capture the potential influence of multi-decadal climate oscillations on wind speed behaviour. For example, using 50- and 60- year time series, previous studies have demonstrated substantial inter-decadal variability in the intensity of winter storm tracks and winter wind intensity along the Pacific coast –50. FurtThe spatial variability in the interannual WD-CUI relationship is likely due to different regional responses to large-scale climate cycles, such as the El-Nino Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO), and related shifts in storm track location.Whereas WD is determined by wind speed behaviour at a specific location, CUI is a weighted aggregate of inflows into BC’s hydroelectric reservoirs, and is therefore dependent on the combined behaviour of all contributing watersheds. Approximately 81% of BC Hydro’s annual hydroelectric generation comes from the Peace and Columbia basins , locatedBoth ENSO and PDO have been shown to be important influences on wind speed, precipitation, and streamflow in the PNW ,51,52, bWind speeds in the PNW are also influenced by ENSO and PDO ,27,33, bThe WD-CUI relationship at a given location is therefore determined by how similar the wind speed behaviour at that site is to the precipitation and streamflow behaviour in the watersheds of the major dam reservoirs, located in the Northern and Southern Interior regions. For example, low inflow years in the interior regions are most likely to occur during negative (cold) ENSO phases, which bring strong winds to coastal areas and weaker winds to interior areas, as seen in Figs Locations whose wind speed behaviour is influenced by factors other than large-scale climate cycles, for example due to location (e.g. on the coast ) or locaThe dominance of hydroelectricity in the PNW, combined with natural variation in precipitation and streamflow, result in large seasonal and interannual fluctuations in potential generation, which can place the electricity system under stress during extreme high and low inflow periods. The value of energy, capacity, and system flexibility vary greatly between high and low inflow conditions ,56, and The widespread weakly positive WD-CUI correlations  suggest The ability of wind power to address energy deficiency in low water years may be of particular interest to BC because strategically targeted wind power development may help to avoid the impacts of hydroelectric overdevelopment and energy surplus in average and wet years. The North Coast region, including Haida Gwaii and smaller areas of southern and northwestern BC and northern Washington, all had significantly increased wind densities in the lowest inflow years . Wind deWind speed behavior during high inflow periods should also be considered when selecting wind farm locations. Due to low or negative electricity prices and a reduced ability to manage reservoir levels because of the non-dispatchable nature of wind power, wind generation during high water periods can be of very little value or even detrimental to the operation of the electricity system ,18,19. WIt should also be noted that while the geographic pattern of WD anomalies was similar for the three and five lowest inflow years, the number and magnitude of significant anomalies were lower in the five-year case. That the WD anomalies were generally larger and more numerous when only considering the three driest years suggests that the drivers of the increases or decreases in WD, such as a shift in the storm track, appear to be more consistent for the absolute driest years, rather than for low precipitation years in general. In particular, the almost complete disappearance of significant anomalies in the Far North, Northern Interior, and South Coast in the five-year low inflow case indicates that the wind speed behaviour in these regions is much less persistent across all low-flow years than in other regions with more consistent anomalies, such as the North Coast.All significant wind density anomalies for the three and five highest inflow years were positive , but werThe different spatial patterns in the three- and five-year high flow anomalies may indicate that the relationships between inflows and WD are less consistent in the wettest years than the driest. This inconsistency, along with the greater importance of understanding WD patterns in low water years to satisfy self-sufficiency requirements, means that high flow anomalies are unlikely to play as large a role in wind farm site selection in BC.However, the WD anomalies for Washington State and Oregon were more consistent and are therefore likely common to high water years in general. The large positive anomalies found in the US Coast and US Interior, and the rapid wind power development occurring in this region, could result in even larger energy surpluses in high water years, rather than the moderating effect that diversification is meant to bring. Because of the tightly integrated nature of the PNW energy system, such an increase in non-dispatchable generation, when reservoir capacity is already limited, is already having consequences for the electricity market in both Canada and the US. The most significant effect is the decline in electricity prices, particularly during the freshet , and theAlong with interannual variability, BC inflows undergo large seasonal variations. For example, the average monthly CUI during the spring freshet (May through July) is more than 7 times larger than an average winter month (December through March). Increased wind power during the low inflow winter months can increase system flexibility, and can help to meet higher energy demands caused by increased heating requirements . ElectriThe largest WD anomalies found during both the winter and freshet time periods were located along the Pacific coast , with deThe large decrease in wind speeds and wind densities during the spring freshet for both the Northern Interior and coastal regions  is anothWhile the PNW is an ideal case study area, the proposed methodology to improve the site selection of wind farms by considering the relative long-term variability of wind speeds and hydroelectric reservoir inflows should be beneficial for many energy systems worldwide. A number of factors will affect whether multi-decadal variability could be an important factor in wind farm site selection, including the nature of climate variation, the existing potential for wind power generation, and the heterogeneity within the energy system.First, the electricity system must contain hydroelectric reservoirs with long-term inflow variability that is large enough to affect system operations or market prices. Such inflow variability could be caused by regular climate cycles , North Atlantic Oscillation (NAO), El Niño Southern Oscillation (ENSO)), seasonal rainfall (e.g. monsoon), or snowmelt conditions (e.g. spring freshet). The potential value of poorly correlated wind resources will increase with the magnitude of the inflow variability, and with the importance of hydroelectric generation within the energy system.Second, there must be substantial wind power potential within the system relative to the total system size or the hydroelectric reservoir capacity. Wind power must have noticeable effects on market prices or reservoir levels for the benefits of increased/decreased wind power during dry/wet periods to outweigh the value of increased total generation at alternative sites.Third, the wind resource must be sufficiently heterogeneous for there to be regional variations in long-term wind speed variability between potential wind farm sites. In the PNW the long-term variability of both wind speeds ,27,33,51While market conditions will determine the nature of the benefits accrued from beneficial wind timing, poorly correlated wind speeds and reservoir inflows can be beneficial in both regulated and deregulated markets. In regulated, or partially regulated, markets, such as BC, wind farms that better complement long-term reservoir inflows can increase energy security and system flexibility, and lower energy costs, which can be passed on to consumers. Similarly, in deregulated markets, building wind farms that reliably generate electricity when prices are higher will increase profitability and decrease market volatility by moderating supply fluctuations.Some prime examples of where this methodology could be beneficial include New Zealand, Norway, and the Canadian province of Quebec. Hydroelectricity provides the majority of electricity generation in all three jurisdictions, ranging from 50–60% in New Zealand ,62. All This study suggests that 30-year relationships between wind speed and reservoir inflow behavior can be examined together to improve wind power site selection. However, there are some limitations to interpreting these results that are based largely on using reanalysis data products to determine wind speed behavior. First, meteorological station coverage in BC is very sparse, with even fewer radiosonde locations, forcing NARR to rely heavily on extrapolating down from modeled higher elevation and boundary winds. Previous studies using reanalysis data have calculated surface wind speed trends that are often inconsistent with those seen in observational data ,63. SomeSecond, the length of the NARR data series (30 years) limits our ability to examine longer, historical trends in wind variability, and can increase the possibility that multi-decadal oscillations, such as the PDO, influence the trends. Other work from the Pacific Coast has suggested slight differences in wind speed intensity trends (less significant compared to NARR) when a longer, 60-year time series from the NCAR/NCEP reanalysis is used . Longer Although our study did not attempt to analyze relationships between climate indices, wind speeds, and hydrological data, we recognize that a longer time series of data could influence the analysis. However, although longer in duration, the NCEP reanalysis has a coarser resolution , which tends to reduce the correspondence between NCEP winds and local observed winds, particularly over the topographically complex terrain of British Columbia . As a reAnother potential limitation of the NARR dataset is that it does not capture the localized variability caused by the highly complex topography of the PNW. The results of this study can therefore only identify regions of interest for further study rather than specific ideal wind farm locations. Correlations between reanalysis wind fields and surface observations are likely to be stronger for coastal sites than for interior sites because of their closer proximity to the climatic conditions over the Pacific Ocean, which are the main drivers of interannual wind speed variation in BC . The strThird, Curry et al. (2012)  also shoFinally, our study represents a historical analysis of trends and wind-hydrology relationships, but the nature of these relationships could change into the future. Some modeling studies have suggested that the Pacific storm track may shift poleward with global warming . While aNevertheless, our analysis provides a means of identifying regions where more detailed analysis with observational data should be prioritized by focusing on areas with low or negative WD-CUI correlations, positive WD anomalies during winter and low inflow years, and negative WD anomalies during the freshet and high inflow years. These areas include northern Vancouver Island, Haida Gwaii, and the broader North Coast region.The province of British Columbia (BC) relies heavily on hydroelectric generation, which experiences large fluctuations in generation potential related to interannual and seasonal fluctuations in reservoir inflows. Electricity generation in low flow years is therefore particularly valuable, when hydroelectric generating potential can decline substantially. Using the wind speed data from the North American Regional Reanalysis (NARR) dataset between 1979 and 2010, this study suggests that northern Vancouver Island, Haida Gwaii, and the broader North Coast region all contain sites with strong, broadly increasing winds and negative correlations between annual wind density (WD) and cumulative usable inflows (CUI) estimated by BC Hydro. As such, wind farm sites in these regions could play a particularly useful role in meeting energy generation requirements in the lowest water years and help to moderate the variability in hydroelectric generation.With a few exceptions , wind densities throughout most of the PNW are also significantly higher during the winter and significantly lower during the freshet, when compared to all other months of the year. The Pacific coast again has the most beneficial seasonal timing, with the largest wind density anomalies during both winter and the freshet, along with the western portions of the Rocky Mountains. Widespread decreases in wind density during freshet when system flexibility is low, and increases during winter when capacity demands are highest, indicate that wind power located nearly anywhere in the province would have somewhat beneficial seasonal timing.While this study has taken a first step in identifying regions with beneficial wind density timing relative to CUI, several additional steps are needed to verify these results. First, this study has identified several interesting candidate regions in BC that should be investigated further by comparing NARR and observational data. In addition to comparisons with existing observational data, there is a need for new meteorological stations that will allow for the testing of the accuracy of NARR’s wind fields and the heterogeneity of the WD-CUI relationships. The inclusion of both surface and turbine height anemometers at these sites would be particularly useful in assessing NARR’s ability to differentiate between surface and boundary layer winds, especially where station data is lacking. Also, wind farms are often located in topographically distinct areas, such as coastlines and ridges. Determining how the wind density behavior at these types of sites compares to the regional results could be important in identifying other regions with beneficial wind timing.A second step would be to quantify the economic value of developing wind projects in regions with beneficial wind speed variability. Many considerations are included when evaluating potential wind farm sites that determine the cost of energy, such as construction, maintenance, and transmission costs, and the predicted energy output over the turbine's lifespan ,71. For S1 TableNumbers in parentheses are the annual rankings. All totals are based on the water year of October through September, referenced by the calendar year containing October to December. The freshet season is defined as May-July, and the winter season is defined as December-March.(DOCX)Click here for additional data file.