Number of Patients Studied Prior to Approval of New Medicines: A Database Analysis
Publication Date
March 19, 2013
Journal
PLOS Medicine
Authors
Ruben G. Duijnhoven, Sabine M. J. M. Straus, June M. Raine, Anthonius De Boer, et al
Volume
10
Issue
3
Pages
e1001407
DOI
https://dx.plos.org/10.1371/journal.pmed.1001407
Publisher URL
http://journals.plos.org/plosmedicine/article?id=10.1371%2Fjournal.pmed.1001407
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23526887
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601954
Europe PMC
http://europepmc.org/abstract/MED/23526887
Web of Science
000316800600011
Scopus
84875425022
Mendeley
http://www.mendeley.com/research/number-patients-studied-prior-approval-new-medicines-database-analysis
Events
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Mendeley | Further Information

{"title"=>"Number of Patients Studied Prior to Approval of New Medicines: A Database Analysis", "type"=>"generic", "authors"=>[{"first_name"=>"Ruben G.", "last_name"=>"Duijnhoven", "scopus_author_id"=>"40461332300"}, {"first_name"=>"Sabine M.J.M.", "last_name"=>"Straus", "scopus_author_id"=>"7102248163"}, {"first_name"=>"June M.", "last_name"=>"Raine", "scopus_author_id"=>"7006281865"}, {"first_name"=>"Anthonius", "last_name"=>"de Boer", "scopus_author_id"=>"56489803600"}, {"first_name"=>"Arno W.", "last_name"=>"Hoes", "scopus_author_id"=>"35370614300"}, {"first_name"=>"Marie L.", "last_name"=>"de Bruin", "scopus_author_id"=>"55648866000"}], "year"=>2013, "source"=>"PLoS Medicine", "identifiers"=>{"scopus"=>"2-s2.0-84875425022", "doi"=>"10.1371/journal.pmed.1001407", "sgr"=>"84875425022", "isbn"=>"1549-1676 (Electronic)\r1549-1277 (Linking)", "pmid"=>"23526887", "issn"=>"15491277", "pui"=>"368602105"}, "id"=>"8178fa2d-0748-37e4-92d3-1066e90f9882", "abstract"=>"Background: At the time of approval of a new medicine, there are few long-term data on the medicine's benefit–risk balance. Clinical trials are designed to demonstrate efficacy, but have major limitations with regard to safety in terms of patient exposure and length of follow-up. This study of the number of patients who had been administered medicines at the time of medicine approval by the European Medicines Agency aimed to determine the total number of patients studied, as well as the number of patients studied long term for chronic medication use, compared with the International Conference on Harmonisation's E1 guideline recommendations. Methods and Findings: All medicines containing new molecular entities approved between 2000 and 2010 were included in the study, including orphan medicines as a separate category. The total number of patients studied before approval was extracted (main outcome). In addition, the number of patients with long-term use (6 or 12 mo) was determined for chronic medication. 200 unique new medicines were identified: 161 standard and 39 orphan medicines. The median total number of patients studied before approval was 1,708 (interquartile range [IQR] 968–3,195) for standard medicines and 438 (IQR 132– 915) for orphan medicines. On average, chronic medication was studied in a larger number of patients (median 2,338, IQR 1,462–4,135) than medication for intermediate (878, IQR 513–1,559) or short-term use (1,315, IQR 609–2,420). Safety and efficacy of chronic use was studied in fewer than 1,000 patients for at least 6 and 12 mo in 46.4% and 58.3% of new medicines, respectively. Among the 84 medicines intended for chronic use, 68 (82.1%) met the guideline recommendations for 6-mo use (at least 300 participants studied for 6 mo and at least 1,000 participants studied for any length of time), whereas 67 (79.8%) of the medicines met the criteria for 12-mo patient exposure (at least 100 participants studied for 12 mo). Conclusions: For medicines intended for chronic use, the number of patients studied before marketing is insufficient to evaluate safety and long-term efficacy. Both safety and efficacy require continued study after approval. New epidemiologic tools and legislative actions necessitate a review of the requirements for the number of patients studied prior to approval, particularly for chronic use, and adequate use of post-marketing studies., of which AdB is the chair and RGD and MLDB are employees, has received unrestricted research funding from the Netherlands Organisation for Health Research and Development (ZonMW), the Dutch Health Care Insurance Board (CVZ), the Royal Dutch Pharmacists Association (KNMP), the private-public funded Top Institute Pharma (www.tipharma.nl, includes co-funding from universities, government, and industry), the EU Innovative Medicines Initiative (IMI), EU 7th Framework Program (FP7), the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health and Industry (including GlaxoSmithKline, Pfizer, and others). The authors declare no other competing interests.", "link"=>"http://www.mendeley.com/research/number-patients-studied-prior-approval-new-medicines-database-analysis", "reader_count"=>65, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>26, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>4, "Student > Master"=>10, "Other"=>7, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>2, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>26, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>4, "Student > Master"=>10, "Other"=>7, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>2, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Biochemistry, Genetics and Molecular Biology"=>1, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>37, "Agricultural and Biological Sciences"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>8, "Business, Management and Accounting"=>3, "Social Sciences"=>2, "Computer Science"=>1, "Economics, Econometrics and Finance"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>37}, "Social Sciences"=>{"Social Sciences"=>2}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>6}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>8}}, "reader_count_by_country"=>{"Canada"=>2, "Netherlands"=>1, "United States"=>2, "United Kingdom"=>1}, "group_count"=>6}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1007506"], "description"=>"<p>Percentages are column percentages.</p>", "links"=>[], "tags"=>["medicines", "categorised", "individuals", "studied"], "article_id"=>668128, "categories"=>["Immunology", "Medicine", "Biotechnology", "Pharmacology"], "users"=>["Ruben G. Duijnhoven", "Sabine M. J. M. Straus", "June M. Raine", "Anthonius de Boer", "Arno W. Hoes", "Marie L. De Bruin"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001407.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_percent_of_medicines_categorised_according_to_total_number_of_individuals_studied_prior_to_marketing_/668128", "title"=>"Number (percent) of medicines categorised according to total number of individuals studied prior to marketing.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-19 02:15:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/991630"], "description"=>"<p>Results for standard (non-orphan) medicines are presented by intended length of use of the products (chronic, intermediate, or short-term) and as one group (sub-total). Boxplots present the 50th percentile, i.e., the median value is given, with the interquartile range (25th and 75th percentiles) indicated by the box, the 2nd and 98th percentiles indicated by the horizontal bars of the whiskers, and outliers indicated by individual circles. The total number of patients studied (<i>y</i>-axis) is plotted on a logarithmic scale.</p>", "links"=>[], "tags"=>["medians", "patients", "studied"], "article_id"=>655504, "categories"=>["Immunology", "Medicine", "Biotechnology", "Pharmacology"], "users"=>["Ruben G. Duijnhoven", "Sabine M. J. M. Straus", "June M. Raine", "Anthonius de Boer", "Arno W. Hoes", "Marie L. De Bruin"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001407.g001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Boxplots_with_medians_of_the_number_of_patients_studied_before_approval_/655504", "title"=>"Boxplots with medians of the number of patients studied before approval.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-20 11:06:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/991633"], "description"=>"<div><p>Background</p><p>At the time of approval of a new medicine, there are few long-term data on the medicine's benefit–risk balance. Clinical trials are designed to demonstrate efficacy, but have major limitations with regard to safety in terms of patient exposure and length of follow-up. This study of the number of patients who had been administered medicines at the time of medicine approval by the European Medicines Agency aimed to determine the total number of patients studied, as well as the number of patients studied long term for chronic medication use, compared with the International Conference on Harmonisation's E1 guideline recommendations.</p> <p>Methods and Findings</p><p>All medicines containing new molecular entities approved between 2000 and 2010 were included in the study, including orphan medicines as a separate category. The total number of patients studied before approval was extracted (main outcome). In addition, the number of patients with long-term use (6 or 12 mo) was determined for chronic medication. 200 unique new medicines were identified: 161 standard and 39 orphan medicines. The median total number of patients studied before approval was 1,708 (interquartile range [IQR] 968–3,195) for standard medicines and 438 (IQR 132–915) for orphan medicines. On average, chronic medication was studied in a larger number of patients (median 2,338, IQR 1,462–4,135) than medication for intermediate (878, IQR 513–1,559) or short-term use (1,315, IQR 609–2,420). Safety and efficacy of chronic use was studied in fewer than 1,000 patients for at least 6 and 12 mo in 46.4% and 58.3% of new medicines, respectively. Among the 84 medicines intended for chronic use, 68 (82.1%) met the guideline recommendations for 6-mo use (at least 300 participants studied for 6 mo and at least 1,000 participants studied for any length of time), whereas 67 (79.8%) of the medicines met the criteria for 12-mo patient exposure (at least 100 participants studied for 12 mo).</p> <p>Conclusions</p><p>For medicines intended for chronic use, the number of patients studied before marketing is insufficient to evaluate safety and long-term efficacy. Both safety and efficacy require continued study after approval. New epidemiologic tools and legislative actions necessitate a review of the requirements for the number of patients studied prior to approval, particularly for chronic use, and adequate use of post-marketing studies.</p> <p> <i>Please see later in the article for the Editors' Summary</i></p> </div>", "links"=>[], "tags"=>["patients", "studied", "analysis"], "article_id"=>655507, "categories"=>["Immunology", "Medicine", "Biotechnology", "Pharmacology"], "users"=>["Ruben G. Duijnhoven", "Sabine M. J. M. Straus", "June M. Raine", "Anthonius de Boer", "Arno W. Hoes", "Marie L. De Bruin"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001407", "stats"=>{"downloads"=>8, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Number_of_Patients_Studied_Prior_to_Approval_of_New_Medicines_A_Database_Analysis__/655507", "title"=>"Number of Patients Studied Prior to Approval of New Medicines: A Database Analysis", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-20 11:07:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1007525"], "description"=>"<p>Sample sizes (number of study participants) required to detect adverse effects of medicines in trials and cohort studies (with required number per study arm and assuming a significance level of 95% [α = 0.05] and power of 80% [β = 0.2]).</p>", "links"=>[], "tags"=>["sizes", "adverse", "medicines", "trials", "cohort", "studies", "assuming"], "article_id"=>668148, "categories"=>["Immunology", "Medicine", "Biotechnology", "Pharmacology"], "users"=>["Ruben G. Duijnhoven", "Sabine M. J. M. Straus", "June M. Raine", "Anthonius de Boer", "Arno W. Hoes", "Marie L. De Bruin"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001407.t003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sample_sizes_number_of_study_participants_required_to_detect_adverse_effects_of_medicines_in_trials_and_cohort_studies_with_required_number_per_study_arm_and_assuming_a_significance_level_of_95_945_8202_8202_0_05_and_power_of_80_946_8202_8202_0_2_/668148", "title"=>"Sample sizes (number of study participants) required to detect adverse effects of medicines in trials and cohort studies (with required number per study arm and assuming a significance level of 95% [α = 0.05] and power of 80% [β = 0.2]).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-19 02:15:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1007544"], "description"=>"<p>Percentages presented are row percentages for 6 and 12 mo use. Products with (1) a total number of patients studied of fewer than 1,000, (2) fewer than 300 studied for 6 mo, or (3) fewer than 100 studied for 12 mo do not meet the guideline criteria, and are shown in bold. For purposes of calculation and display, missing data were assumed to be in compliance with the recommended patient exposures.</p>", "links"=>[], "tags"=>["medicines", "categorised", "individuals", "studied", "12", "mo"], "article_id"=>668167, "categories"=>["Immunology", "Medicine", "Biotechnology", "Pharmacology"], "users"=>["Ruben G. Duijnhoven", "Sabine M. J. M. Straus", "June M. Raine", "Anthonius de Boer", "Arno W. Hoes", "Marie L. De Bruin"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001407.t002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_percent_of_medicines_categorised_according_to_total_number_of_individuals_studied_for_6_and_12_mo_long_term_prior_to_marketing_/668167", "title"=>"Number (percent) of medicines categorised according to total number of individuals studied for 6 and 12 mo (long term) prior to marketing.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-19 02:16:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/991631"], "description"=>"<p>Reference lines are added to indicate the minimum criteria from the ICH E1 guideline: 1,000 patients in total and 300 and 100 patients studied for 6 and 12 mo, respectively. Any products not meeting the ICH E1 guideline recommendations are shown in red.</p>", "links"=>[], "tags"=>["displaying", "patients", "studied", "plotted", "12"], "article_id"=>655505, "categories"=>["Immunology", "Medicine", "Biotechnology", "Pharmacology"], "users"=>["Ruben G. Duijnhoven", "Sabine M. J. M. Straus", "June M. Raine", "Anthonius de Boer", "Arno W. Hoes", "Marie L. De Bruin"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001407.g002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Scatterplot_displaying_the_total_number_of_patients_studied_before_approval_plotted_against_the_number_of_patients_studied_long_term_for_6_and_12_mo_for_chronic_medication_/655505", "title"=>"Scatterplot displaying the total number of patients studied before approval plotted against the number of patients studied long term (for 6 and 12 mo) for chronic medication.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-20 11:07:10"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"48", "full-text"=>"44", "pdf"=>"27", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"19", "full-text"=>"17", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"16", "full-text"=>"11", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"11", "full-text"=>"7", "pdf"=>"6", "abstract"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"14", "full-text"=>"17", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"15", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"40", "full-text"=>"44", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"8", "full-text"=>"14", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"2", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"5", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"22", "full-text"=>"20", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"11", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"15", "full-text"=>"17", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"18", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"24", "full-text"=>"29", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"4", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"2", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"22", "full-text"=>"22", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"16", "full-text"=>"18", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"24", "full-text"=>"26", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"25", "full-text"=>"30", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"2", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"23", "full-text"=>"28", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"21", "full-text"=>"26", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"32", "full-text"=>"29", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"20", "full-text"=>"25", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"38", "full-text"=>"41", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"20", "full-text"=>"23", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"47", "full-text"=>"45", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"39", "full-text"=>"44", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"63", "full-text"=>"72", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"44", "full-text"=>"50", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"43", "full-text"=>"43", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"48", "full-text"=>"55", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"36", "full-text"=>"41", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"55", "full-text"=>"65", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Medicine and health sciences/Clinical medicine", "average_usage"=>[263, 451, 582, 699, 797, 889, 969, 1045, 1134, 1215, 1284, 1362, 1412]}, {"subject_area"=>"/Medicine and health sciences/Pharmaceutics", "average_usage"=>[254, 457, 591, 700, 808, 906, 1001, 1093, 1185, 1276, 1373, 1457, 1535]}, {"subject_area"=>"/Social sciences/Sociology", "average_usage"=>[310, 523, 656, 780, 900, 1024, 1120, 1219, 1308, 1395, 1468, 1570, 1642]}]}
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