Atjaunināt sīkdatņu piekrišanu

E-grāmata: Clinical Trials: Study Design, Endpoints and Biomarkers, Drug Safety, and FDA and ICH Guidelines

4.45/5 (12 ratings by Goodreads)
(Consultant for Second Genome, Inc. (Crohn's disease), Rigel Pharmaceuticals (platelet disorder), PrimeGen Biotech (stem cell therapy), Regeneron Pharmaceuticals (broadly neutralizing antibodies for HIV), and Biogen IDEC (multiple scleros)
  • Formāts: EPUB+DRM
  • Izdošanas datums: 19-Feb-2016
  • Izdevniecība: Academic Press Inc
  • Valoda: eng
  • ISBN-13: 9780128042588
Citas grāmatas par šo tēmu:
  • Formāts - EPUB+DRM
  • Cena: 80,19 €*
  • * ši ir gala cena, t.i., netiek piemērotas nekādas papildus atlaides
  • Ielikt grozā
  • Pievienot vēlmju sarakstam
  • Šī e-grāmata paredzēta tikai personīgai lietošanai. E-grāmatas nav iespējams atgriezt un nauda par iegādātajām e-grāmatām netiek atmaksāta.
Clinical Trials: Study Design, Endpoints and Biomarkers, Drug Safety, and FDA and ICH GuidelinesPalielināt
  • Formāts: EPUB+DRM
  • Izdošanas datums: 19-Feb-2016
  • Izdevniecība: Academic Press Inc
  • Valoda: eng
  • ISBN-13: 9780128042588
Citas grāmatas par šo tēmu:

DRM restrictions

  • Kopēšana (kopēt/ievietot):

    nav atļauts

  • Drukāšana:

    nav atļauts

  • Lietošana:

    Digitālo tiesību pārvaldība (Digital Rights Management (DRM))
    Izdevējs ir piegādājis šo grāmatu šifrētā veidā, kas nozīmē, ka jums ir jāinstalē bezmaksas programmatūra, lai to atbloķētu un lasītu. Lai lasītu šo e-grāmatu, jums ir jāizveido Adobe ID. Vairāk informācijas šeit. E-grāmatu var lasīt un lejupielādēt līdz 6 ierīcēm (vienam lietotājam ar vienu un to pašu Adobe ID).

    Nepieciešamā programmatūra
    Lai lasītu šo e-grāmatu mobilajā ierīcē (tālrunī vai planšetdatorā), jums būs jāinstalē šī bezmaksas lietotne: PocketBook Reader (iOS / Android)

    Lai lejupielādētu un lasītu šo e-grāmatu datorā vai Mac datorā, jums ir nepieciešamid Adobe Digital Editions (šī ir bezmaksas lietotne, kas īpaši izstrādāta e-grāmatām. Tā nav tas pats, kas Adobe Reader, kas, iespējams, jau ir jūsu datorā.)

    Jūs nevarat lasīt šo e-grāmatu, izmantojot Amazon Kindle.

Clinical Trials, Second Edition, offers those engaged in clinical trial design a valuable and practical guide. This book takes an integrated approach to incorporate biomedical science, laboratory data of human study, endpoint specification, legal and regulatory aspects and much more with the fundamentals of clinical trial design. It provides an overview of the design options along with the specific details of trial design and offers guidance on how to make appropriate choices. Full of numerous examples and now containing actual decisions from FDA reviewers to better inform trial design, the 2nd edition ofClinical Trials is a must-have resource for early and mid-career researchers and clinicians who design and conduct clinical trials.
  • Contains new and fully revised material on key topics such as biostatistics, biomarkers, orphan drugs, biosimilars, drug regulations in Europe, drug safety, regulatory approval and more
  • Extensively covers the "study schema" and related features of study design
  • Incorporates laboratory data from studies on human patients to provide a concrete tool for understanding the concepts in the design and conduct of clinical trials
  • Includes decisions made by FDA reviewers when granting approval of a drug as real world learning examples for readers

Papildus informācija

A hands-on guidebook that integrates the most practical aspects of clinical trial design with important content on laboratory studies of human data, patient safety, regulatory requirements and much more
Acknowledgments xv
Preface xvii
Introduction xxiii
Abbreviations and Definitions xxvii
Biographies xxxi
1 Origins of Drugs
I Introduction
1(1)
II Structures of Drugs
2(6)
III The 20 Classical Amino Acids
8(3)
IV Animal Models
11(10)
V Estimating Human Dose from Animal Studies
21(3)
VI Origin of Drugs that are Biosimilars
24(1)
VII Origin of Drugs that are Orphan Drugs
25(4)
VIII Summary
29(2)
2 Clinical Trial Design
I Introduction to Regulated Clinical Trials
31(4)
II Study Design
35(1)
III The Study Schema
36(22)
IV Further Concepts in Clinical Trial Design
58(7)
V FDA's Decision-Making Processes Regarding Dose Modification and Discontinuation
65(1)
VI Amendments to the Clinical Study Protocol
66(2)
VII Concluding Remarks
68(1)
3 Run-in Period
I Introduction
69(9)
II FDA's Decision-Making Processes in Evaluating Run-in Period
78(2)
III Concluding Remarks
80(3)
4 Inclusion/Exclusion Criteria, Stratification, and Subgroups-Part I
I The Clinical Study Protocol is a Manual that Provides the Study Design
83(14)
II Biochemistry of Drug Resistance
97(5)
III FDA's Warning Letters and Inclusion/Exclusion Criteria
102(1)
IV Subgroups and Subgroup Analysis
103(5)
V FDA's Decision-Making Processes in Evaluating Stratification and Subgroups
108(5)
VI Concluding Remarks
113(2)
5 Inclusion/Exclusion Criteria, Stratification, and Subgroups-Part II
I Introduction
115(1)
II Staging
115(6)
III Staging Systems for Various Cancers
121(7)
IV The Will Rogers Phenomenon
128(3)
V Other Sources of Artifacts in Data from Clinical Trials
131(1)
VI Concluding Remarks
131(2)
6 Blinding, Randomization, and Allocation
I Introduction
133(3)
II Logistics of Keeping Track of Study Subjects
136(6)
III Blocked Randomization
142(2)
IV Clinical Study Protocol Randomization Instructions
144(1)
V Instructions for Unblinding
145(2)
VI Summary of Unblinding
147(1)
VII FDA Warning Letters
148(1)
VIII Interactive Voice Response Systems
149(4)
IX Concluding Remarks
153(2)
7 Placebo Arm as Part of Clinical Trial Design
I Introduction
155(1)
II Hawthorne Effect
156(1)
III The No-Treatment Arm
157(1)
IV Physical Aspects of the Placebo
157(1)
V Active Placebo
158(1)
VI Subjects in the Placebo Arm May Receive Best Supportive Care or Palliative Care
158(2)
VII Clash Between BSC and the Endpoint of HRQoL
160(1)
VIII Ethics of Placebos
160(5)
IX FDA's Decision-Making Process in Evaluating the Placebo Arm
165(4)
X Standard of Care
169(4)
8 Intent-to-Treat Analysis versus Per Protocol Analysis
I Introduction
173(3)
II ITT Analysis Contrasted With PP Analysis
176(3)
III Disadvantages of ITT Analysis
179(1)
IV Run-In Period, as Part of the Study Design, is Relevant to ITT Analysis and PP Analysis
180(1)
V Summary
180(1)
VI Hypothetical Example Where Study Drug and Control Drug Have the Same Efficacy
181(1)
VII Modified ITT Analysis
181(11)
VIII Start Date for Endpoints in Clinical Trials
192(2)
IX FDA's Decision-Making Processes, Relating to ITT Analysis and PP Analysis
194(6)
X Concluding Remarks
200(3)
9 Biostatistics-Part I
I Introduction
203(5)
II Definitions and Formulas
208(1)
III Data from the Study of Machin and Gardner
209(1)
IV Data Used for Constructing the Kaplan-Meier Plot are from Subjects Enrolling at Different Times
210(1)
V Sample versus Population
211(1)
VI What can be Compared
212(1)
VII One-Tailed Test versus Two-Tailed Test
212(2)
VIII P Value
214(2)
IX Calculating the P Value-A Working Example
216(6)
X Summary
222(1)
XI Theory Behind the Z Value and the Table of Areas in Tail of the Standard Normal Distribution
222(1)
XII Statistical Analysis by Superiority Analysis versus by Noninferiority Analysis
223(4)
10 Biostatistics-Part II
Jennifer Elder
I Introduction
227(1)
II Discussions that Impact Sample Size Determination
227(3)
III Statistical Terms Commonly Used in Sample Size Calculations
230(1)
IV Null and Alternative Hypotheses
230(1)
V Degree of Certainty: Alpha and Beta
231(1)
VI Statistical Methods for Determining Trial Size
231(1)
VII Continuous Variables: Testing the Difference Between Two Means
231(3)
VIII Changes in Sample Size Assumptions can Yield Dramatic Changes to Sample Size
234(1)
IX Changing Assumptions About Alpha or Beta
235(1)
X Changing Assumptions About Theta
236(1)
XI Binary Variables: Testing the Difference Between Two Proportions
237(2)
XII Time to Event Variables: Testing for Differences Between Two Groups Using the Logrank Test
239(2)
XIII Binary Variable: Testing for Equivalence of Two Proportions
241(2)
XIV Other Helpful Considerations
243(1)
XV Writing a Sample Size Section of a Clinical Study Protocol
244
11 Introduction to Endpoints
I FDA's Guidance for Industry
247(6)
12 Oncology Endpoint-Objective Response
I Introduction to Endpoints in Oncology Clinical Trials
253(9)
II Studies Characterizing an Association Between Objective Response and Survival
262(1)
III Avoiding Confusion When Using Objective Response as an Endpoint
263(3)
IV FDA's Decision-Making Process in Evaluating Objective Response
266(2)
V Concluding Remarks
268(1)
13 Oncology Endpoints: Overall Survival and Progression-Free Survival
I Introduction
269(3)
II Advantages of PFS Over Overall Survival
272(2)
III Advantages of Overall Survival Over PFS
274(1)
IV Guidance From Clinical Trials on Using Endpoints
275(12)
V Concluding Remarks
287(2)
14 Oncology Endpoints: Time to Progression
I Introduction
289(1)
II Agreement of Results from Objective Response, TTP, and Overall Survival-The Paccagnella Study
290(1)
III Can the Value for PFS be Less Than the Value for TTP?
290(1)
IV Data on the Endpoint of TTP can be Used to Gain FDA-Approval
291(1)
V TTP may be the Preferred Endpoint Where, Once the Trial is Concluded, Patients Receive Additional Chemotherapy-The Park Study
291(1)
VI The Endpoint of TTP may be Preferred Over Survival Endpoints, Where Deaths Result from Causes Other Than Cancer-The Llovet Study
292(3)
VII The Endpoint of Overall Survival may be Preferred Over Objective Response or Over TTP, Where the Drug Is Classed as a Cytostatic Drug-The Llovet Study
295(1)
VIII TTP may Show Efficacy, Where the Endpoint of Overall Survival Fails to Show Efficacy, Where the Number of Subjects is Small-The McDermott Study
296(1)
IX TTP may Show Efficacy, Where the Endpoint of Overall Survival Failed to Show Efficacy, Where the Duration of the Trial was Too Short-The Cappuzzo Study
297(1)
X Methodology Tip-Advantage of Using an Endpoint that Incorporates a "Median" Tune
298(1)
XI Summary
298(1)
XII Thymidine Phosphorylase as a Biomarker for Survival-The Meropol Study
299(1)
XIII Drug Combinations that Include Capecitabine
300(1)
XIV Methodology Tip-Do Changes in mRNA Expression Result in Corresponding Changes in Expression of Polypeptide?
300(1)
XV Concluding Remarks
301(2)
15 Oncology Endpoint: Disease-Free Survival
I Introduction
303(1)
II Difference Between DFS and PFS
304(1)
III Ambiguity in the Name of the Endpoint, "DFS"
304(1)
IV Disease-Free Survival Provides Earlier Results on Efficacy Than Overall Survival-The Add-On Breast Cancer Study of Romond
305(2)
V Disease-Free Survival as an Endpoint in the Analysis of Subgroups-The Add-On Breast Cancer Study of Hayes
307(1)
VI Neoadjuvant Therapy versus Adjuvant Therapy for Rectal Cancer-The Roh Study
308(1)
VII Where Efficacy of Two Different Treatments is the Same, Choice of Treatment Shifts to the Treatment that Improves Quality of Life-The Ring Study
309(1)
VIII DFS and Overall Survival are Useful Tools for Testing and Validating Prognostic Biomarkers-The Bepler Study
310(1)
IX FDA's Decision-Making Process in Evaluating the Endpoint of DFS
311(1)
X Summary
312(1)
16 Oncology Endpoint: Time to Distant Metastasis
I Introduction
313(1)
II TDM Data are Acquired Before Overall Survival Data are Acquired-The Wee Study
314(1)
III Time to Distant Metastasis Data can Reveal a Dramatic Advantage of the Study Drug, in a Situation Where Overall Survival Fails to Show Any Advantage-The Roach Study
315(2)
IV Use of a Gene Array as a Prognostic Factor for Breast Cancer Patients, Using the Endpoint of TDM-The Loi Study
317(1)
V Use of Micro-RNA Expression Data as a Prognostic Factor for Breast Cancer Patients-The Foekens Study
317(1)
VI Biology of miRNA
318(1)
VII Concluding Remarks
319(4)
17 Neoadjuvant Therapy versus Adjuvant Therapy
I Advantages of Neoadjuvant Therapy
323(3)
II Advantages of Adjuvant Therapy
326(1)
III Two Meanings of the Word Adjuvant
327(1)
IV Summary of Neoadjuvant Versus Adjuvant Therapy in Cancer
328(1)
V Induction Therapy versus Maintenance Therapy in Autoimmune Diseases
328(2)
VI Conclusions
330(1)
18 Hematological Cancers
I Introduction
331(17)
II Myelodysplastic Syndromes
348(6)
III Summary
354(1)
IV Cytogenetics of Hematological Cancers
354(9)
V Chromosomal Abnormalities in Solid Tumors
363(1)
VI Endpoints in Hematological Cancers
364(3)
VII Cytogenetics as a Prognostic Marker-The Greyer Study of CLL
367(1)
VIII Minimal Residual Disease
368(7)
IX Confluence of Cytogenetics and Gene Expression
375(1)
X Concluding Remarks
375(2)
19 Biomarkers
I Introduction
377(13)
II Methodology Tip-Microarrays
390(4)
III C-Reactive Protein
394(6)
IV Biomarkers-Specialized Topics
400(3)
V Exploring New Types of Biomarkers
403(5)
VI Single Nucleotide Polymorphisms
408(3)
VII Validating Biomarkers
411(2)
VIII Biomarker Validation from FDA Submissions for In Vitro Diagnostics Tests
413(5)
IX Concluding Remarks
418(3)
20 Endpoints for Immune Diseases
I Introduction
421(1)
II Subsets of Multiple Sclerosis
421(13)
III FDA's Decision-Making Process in Evaluating Endpoints for Multiple Sclerosis
434(2)
IV Concluding Remarks
436(1)
21 Endpoints for Infections
I Introduction
437(1)
II Clinical and Immunological Features of HCV Infections
437(1)
III Acute HCV versus Chronic HCV
438(1)
IV Drugs Against HCV
439(3)
V Immune Responses Against HCV
442(1)
VI Kinetics of HCV Infections
443(3)
VII Responders versus Nonresponders
446(1)
VIII Endpoints in Clinical Trials Against HCV
447(3)
IX Concluding Remarks
450(1)
22 Health-Related Quality of Life Tools-Oncology
I Introduction
451(2)
II Summary
453(1)
III HRQoL Tools Take on Increased Importance When Capturing Data on Adverse Events, or in Trials on Palliative Treatments
454(1)
IV Scheduling the Administration of HRQoL Tools
455(1)
V HRQoL Tools in Oncology
455(12)
VI Decisions on Counseling; Decisions on Chemotherapy versus Surgery
467(1)
VII Concluding Remarks
467(2)
23 Health-Related Quality-of-Life Tools-Immune Disorders
I Introduction
469(1)
II Short Form SF-36 Questionnaire
469(4)
III HRQoL Instruments Specific for Multiple Sclerosis
473(4)
IV Concluding Remarks
477(2)
24 Health-Related Quality-of-Life Tools-Infections
I Introduction
479(1)
II HRQoL Tools With Chronic HCV
480(3)
25 Drug Safety
I Introduction
483(9)
II Safety Definitions
492(10)
III QT Interval Prolongation
502(12)
IV Stevens-Johnson Syndrome
514(2)
V Idiosyncratic Drug Reactions
516(2)
VI FDA's Decision-Making Process in Evaluating Adverse Events
518(1)
VII Drug-Induced Liver Injury
519(3)
VIII Assessing Causality
522(3)
IX Paradoxical Adverse Drug Reactions
525(4)
X Capturing Adverse Events
529(6)
XI FDA's Warning Letters About Failure to Report SAES
535(3)
XII Drugs that Create Risk for Infections
538(3)
XIII FDA's Decision-Making Process on Adverse Events that Appear Irrelevant to the Study Drug
541(1)
XIV Postmarketing Reporting of Adverse Events
542(4)
XV Risk Minimization Tools
546(7)
XVI FDA's Decision-Making Process in Evaluating Risk Minimization Tools
553(4)
XVII European Union's Risk Management Tools
557(1)
XVIII Summary
558(1)
XIX Patient-Reported Outcome
558(2)
XX Summary of Reporting Systems
560(1)
XXI Data and Safety Monitoring Committee
561(7)
XXII Concluding Remarks
568(1)
26 Mechanism of Action of Diseases and Drugs-Part I
I Introduction
569(2)
II MOA and the Package Insert
571(1)
III MOA and Surrogate Endpoints
571(1)
IV MOA and Expected Adverse Drug Reactions
572(1)
V FDA's Warning Letter Regarding Assessing Safety of the Study Drug, According to Its Membership in a Particular Class of Drugs
572(1)
VI MOA and Drug Combinations
573(1)
VII MOA of Diseases With an Immune Component
574(5)
VIII Immune System Pathology in Inflammatory Disorders
579(3)
IX Cells of the Immune System
582(2)
X Drugs that Modulate the Immune System
584(6)
XI Immunology can be Organized as Pairs of Concepts
590(4)
XII Concluding Remarks
594(1)
27 Mechanism of Action-Part II (Cancer)
I Introduction
595(12)
II Immune Evasion
607(2)
III Concluding Remarks
609(2)
28 Mechanism of Action-Part III (Immune Disorders)
I Introduction
611(5)
II Detailed Mechanism of Action of Multiple Sclerosis
616(8)
III Animal Models of Multiple Sclerosis
624(1)
IV Etiology and Mechanisms of Multiple Sclerosis
625(3)
V Diagram of Multiple Sclerosis Mechanism
628(1)
VI Additional Mechanisms of Action in Multiple Sclerosis
629(4)
VII Concluding Remarks
633(2)
29 Mechanisms of Action-Part IV (Infections)
I Introduction
635(1)
II HCV Infections
635(2)
III Life Cycle of HCV
637(1)
IV Initiating Biosynthesis of the HCV Polypeptide
638(1)
V Membranous Web and Lipid Droplet
638(1)
VI NS3/4A Protease
639(1)
VII NS5A-HCV's Recruiting and Assembly Protein
639(2)
VIII NS5B-HCV's RNA Polymerase
641(1)
IX E1 and E2-HCV's Envelope Proteins
642(1)
X Core Protein of HCV
642(1)
XI Innate Immune Response Against HCV
643(2)
XII Chronic Inflammation
645(2)
XIII Oncogenes and Growth Factors
647(3)
XIV Acquired Immune Response Against HCV
650(11)
XV Concluding Remarks
661(2)
30 Consent Forms
I Introduction
663(3)
II Sources of the Law in the United States
666(1)
III Guidance for Industry
666(2)
IV Distinction Between Stopping Treatment and Withdrawing From the Study
668(1)
V Ethical Doctrines
668(1)
VI The Case Law
669(1)
VII Basis for Consent Forms in the CFR
669(2)
VIII Summary
671(1)
IX Examples of Contemporary Consent Forms
671(9)
X Ethical Issues Specific to Phase I Clinical Trials in Oncology
680(1)
XI FDA's Warning Letters
680(3)
XII Decision Aids
683(3)
XIII Concluding Remarks
686(3)
31 Package Inserts
I Introduction
689(6)
II Drug-Drug Interactions
695(6)
III FDA's Decision-Making Process in Evaluating Drug-Drug Interactions
701(5)
IV Summary of Drug-Drug Interactions
706(1)
V Animal Toxicity Data and the Package Insert
706(2)
VI Summary
708(1)
VII Brand Names, Chemical Names, Packaging
708(3)
VIII Ambiguous Writing on Package Inserts
711(1)
IX Package Insert May Protect Manufacturer From Liability
712(4)
X Package Insert Compared With Consent Form
716(1)
XI Relation Between Package Inserts to the Standard of Care, and to Off-Label Uses
716(2)
XII Concluding Remarks
718(1)
32 Warning Letters
I Introduction
719(1)
II List of Topics
720(1)
III Warning Letter Describing Authority of FDA Inspectors
720(1)
IV Anecdotal Description of an FDA Inspection, FDA's Requirements for Record Keeping During Drug Manufacture, and Guidance for Responding to FDA's Complaints
721(1)
V FDA's Warning Letter Distinguished from FDA's Form 483 Notice
722(3)
VI Warning Letter on Corrective Responses, by Sponsor, for a Tumor Clinical Trial
725(1)
VII Definitions
726(1)
VIII Failure of Sponsor to have an FDA-approved IND
727(2)
IX Institutional Review Board
729(16)
X Consent Forms
745(1)
XI Data Monitoring Committee (DMC)
746(3)
XII Protocol Deviations
749(5)
XIII Clinical Hold
754(1)
XIV Concomitant Medications
755(2)
XV Inclusion/Exclusion Criteria
757(1)
XVI Drug Accountability, Drug Storage, Drug Dispensing, and Record Keeping
757(5)
XVII Withdrawal of Subjects From the Clinical Trial
762(4)
XVIII Contract Research Organizations
766(3)
XIX Case Report Forms
769(3)
XX Investigator's Brochure
772(1)
XXI Off-Label Uses
772(6)
XXII Conclusion
778(3)
33 Regulatory Approval
I Origins of the Federal Food, Drug and Cosmetic Act and Its Amendments
781(1)
II Federal Food, Drug and Cosmetic Act of 1938
782(2)
III Drug Amendments Act of 1962
784(1)
IV FDA Modernization Act of 1997 and Phase IV Clinical Trials
784(1)
V History of European Medicines Agency
785(2)
VI International Conference on Harmonisation
787(1)
VII History of the Medicines and Healthcare Products Regulatory Agency
788(1)
VIII Outline of Regulatory Approval in the United States
789(1)
IX Investigational New Drug
790(3)
X IND and the Common Technical Document
793(3)
XI Institutional Review Board
796(2)
XII Timeline of FDA Approval
798(5)
XIII Special Protocol Assessment
803(1)
XIV Target Product Profile
804(1)
XV Company Core Data Sheet
805(1)
XVI Accelerated Approval
806(2)
XVII Refuse to File
808(2)
XVIII Clinical Hold
810(1)
XIX Exemplary Account of FDA Timeline, After Submission of NDA or BLA
811(1)
XX FDA Approval Letter
812(2)
XXI FDA Feedback at Time of Issue of the FDA Approval Letter
814(6)
XXII Processes of Administering Clinical Trials
820(9)
34 Patents
I Introduction
829(1)
II Services Provided by the Patent Attorney or Agent
829(3)
III History of Patenting
832(2)
IV Outline of the Patenting Process
834(2)
V Types of Patent Documents
836(1)
VI Organization of Information in a Patent
837(2)
VII Time-line for Patenting
839(2)
VIII Provisional Patent Applications
841(1)
IX Sources of the Law for Patenting
842(3)
X Intersections Between the FDA Review Process and Patents
845(2)
Index 847
Dr. Tom Brody received his PhD from the University of California at Berkeley in 1980, and conducted postdoctoral research at University of Wisconsin-Madison and also at U.C. Berkeley. His 20 research publications concern the metabolism and pharmacology of folates, cloning an anti-cancer gene (XPE gene), and the structure of an antibody (natalizumab) used for treating multiple sclerosis. The author has 15 years of pharmaceutical industry experience, acquired at Schering-Plough, Cerus Corporation, and Elan Pharmaceuticals, and has contributed to FDA submissions for the indications of multiple sclerosis, melanoma, head and neck cancer, liver cancer, pancreatic cancer, and hepatitis C. At an earlier time, he wrote two editions of Clinical Trials, published by Elsevier, Inc. The author has 16 years of training and experience in the Code of Federal regulations, as it applies to pharmaceuticals and clinical trial design.
Biežāk uzdotie jautājumi par e-grāmatām Biežāk uzdotie jautājumi par e-grāmatām
Permanent link: https://www.kriso.lv/db/97801280425886e.html
Keywords: