Water quality - Guidance on statistical interpretation of ecotoxicity data

This Technical Specification offers guidance on statistical methods used for the analysis of data of
standardized ecotoxicity tests. It focuses on statistical methods for obtaining statistical estimates of
parameters in current and future use, e.g. ECx (LCx), NOEC, NEC. The methods described are intended to cover laboratory ecotoxicity tests (aquatic, sediment and/or terrestrial tests), and may also be relevant for other toxicity tests. The main objective of this Technical Specification is to provide practical guidance on how to analyse the observations from ecotoxicity tests. Hypothesis testing, concentration-response modelling and biology-based modelling are discussed for the different data types (quantal, continuous and discrete data, corresponding to mortality, growth or reproduction). In addition, some guidance on experimental design is given. Although the main focus is on giving assistance to the experimentalist, a secondary aim is to help those who are responsible for evaluating toxicity tests. Finally, the document may be helpful in developing new toxicity test guidelines by giving information on experimental design and statistical analysis issues.

Qualité de l'eau - Lignes directrices relatives à l'interprétation statistique de données écotoxicologiques

Kakovost vode - Navodilo za statistično interpretacijo ekotoksikoloških podatkov

Ta tehnična specifikacija podaja navodilo za statistične metode, ki se uporabljajo za analizo podatkov standardiziranih ekotoksikoloških preskusov. Osredotoča se na statistične metode za pridobivanje statističnih ocen parametrov v trenutni in prihodnji uporabi, npr. ECx (LCx), NOEC, NEC. Opisane metode zajemajo laboratorijske ekotoksikološke preskuse (preskusi vode, sedimentov in/ali zemlje) in so lahko primerne tudi za druge toksikološke preskuse. Glavni namen te tehnične specifikacije je zagotavljanje praktičnih navodil za analizo opažanj pri ekotoksikoloških preskusih. Obravnavano je preskušanje hipotez, modeliranje razmerja med koncentracijo in odzivom ter modeliranje na biološki osnovi za različne vrste podatkov (kvantalne, zvezne in posamične podatke, ki ustrezajo umrljivosti, rasti ali razmnoževanju). Poleg tega je podanih nekaj navodil za snovanje poskusov. Čeprav se v glavnem osredotoča na pomoč izvajalcu poskusa, pomaga tudi tistim, ki so odgovorni za vrednotenje toksikoloških preskusov. Končno je dokument lahko uporaben tudi pri razvijanju smernic za nove toksikološke preskuse, saj podaja informacije o snovanju poskusov in statistični analizi.

General Information

Status
Published
Public Enquiry End Date
19-Jul-2009
Publication Date
05-Jul-2010
Technical Committee
Current Stage
6060 - National Implementation/Publication (Adopted Project)
Start Date
12-May-2010
Due Date
17-Jul-2010
Completion Date
06-Jul-2010

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TECHNICAL ISO/TS
SPECIFICATION 20281
First edition
2006-04-01

Water quality — Guidance on statistical
interpretation of ecotoxicity data
Qualité de l'eau — Lignes directrices relatives à l'interprétation
statistique de données écotoxicologiques




Reference number
ISO/TS 20281:2006(E)
©
ISO 2006

---------------------- Page: 1 ----------------------
ISO/TS 20281:2006(E)
PDF disclaimer
This PDF file may contain embedded typefaces. In accordance with Adobe's licensing policy, this file may be printed or viewed but
shall not be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In
downloading this file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat
accepts no liability in this area.
Adobe is a trademark of Adobe Systems Incorporated.
Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation
parameters were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In
the unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given below.


©  ISO 2006
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,
electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or
ISO's member body in the country of the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
Web www.iso.org
Published in Switzerland

ii © ISO 2006 – All rights reserved

---------------------- Page: 2 ----------------------
ISO/TS 20281:2006(E)
Contents Page
Foreword.xii
Introduction .xiii
1 Scope .1
2 Normative references .1
3 Terms and definitions .1
4 General statistical principles.8
4.1 Different statistical approaches .8
4.1.1 General.8
4.1.2 Hypothesis-testing methods .8
4.1.3 Concentration-response modelling methods .10
4.1.4 Biology-based methods .11
4.2 Experimental design issues .11
4.2.1 General.11
4.2.2 NOEC or EC : Implications for design.12
x
4.2.3 Randomization .12
4.2.4 Replication.13
4.2.5 Multiple controls included in the experimental design.13
4.3 Process of data analysis.14
4.3.1 General.14
4.3.2 Data inspection and outliers.14
4.3.3 Data inspection and assumptions .15
4.3.3.1 Scatter .15
4.3.3.2 Heterogeneous variances and distribution .15
4.3.3.3 Heterogeneous variances and true variation in response.16
4.3.3.4 Consequences for the analysis .16
4.3.4 Transformation of data.16
4.3.5 Parametric and non-parametric methods .17
4.3.5.1 General .17
4.3.5.2 Parametric methods.17
4.3.5.3 Generalized linear models (GLMs) .18
4.3.5.4 Non-parametric methods.18
4.3.5.5 How to choose?.18
4.3.6 Pre-treatment of data.19
4.3.7 Model fitting.19
4.3.8 Model checking.20
4.3.8.1 Analysis of residuals .20
4.3.8.2 Validation of fitted dose-response model .21
4.3.9 Reporting the results.21
5 Hypothesis testing.21
5.1 Introduction.21
5.1.1 General.21
5.1.2 NOEC: What it is, and what it is not.25
5.1.3 Hypothesis used to determine NOEC.25
5.1.3.1 Understanding the question to be answered .25
5.1.3.2 One-sided hypothesis.26
5.1.3.3 Two-sided trend test .26
5.1.3.4 Trend or pair-wise test.26
5.1.4 Comparisons of single-step (pair-wise comparisons) or step-down trend tests to
determine the NOEC.28
© ISO 2006 – All rights reserved iii

---------------------- Page: 3 ----------------------
ISO/TS 20281:2006(E)
5.1.4.1 General discussion . 28
5.1.4.2 Single-step procedures. 28
5.1.4.3 Step-down procedures. 29
5.1.4.4 Deciding between the two approaches . 30
5.1.5 Dose metric in trend tests . 31
5.1.6 Role of power in toxicity experiments . 31
5.1.7 Experimental design . 32
5.1.8 Treatment of covariates and other adjustments to analysis. 33
5.2 Quantal data (e.g. mortality, survival). 34
5.2.1 Hypothesis testing with quantal data to determine NOEC values . 34
5.2.2 Parametric versus non-parametric tests .35
5.2.2.1 Basis . 35
5.2.2.2 Single-step procedures. 36
5.2.2.3 Step-down procedures. 36
5.2.2.3.1 Choice of step-down procedure. 36
5.2.2.3.2 Test for monotone dose response . 36
5.2.2.3.3 Analysing the monotonic response for quantal data — Step-down procedure . 37
5.2.2.3.4 Possible modifications of the step-down procedure. 37
5.2.2.4 Alternative procedures . 37
5.2.2.4.1 Parametric and non-parametric procedures. 37
5.2.2.4.2 Pair-wise ANOVA-based methods . 38
5.2.2.4.3 Jonckheere-Terpstra trend test.38
5.2.2.4.4 Poisson tests . 38
5.2.2.5 Assumptions of methods for determining NOEC values . 38
5.2.3 Additional information. 39
5.2.4 Statistical items to be included in the study report. 40
5.3 Hypothesis testing with continuous data (e.g. mass, length, growth rate) to determine
NOEC . 40
5.3.1 General . 40
5.3.2 Parametric versus non-parametric tests .41
5.3.3 Single-step (pair-wise) procedures . 42
5.3.3.1 General . 42
5.3.3.2 Dunnett's test. 42
5.3.3.3 Tamhane-Dunnett test. 42
5.3.3.4 Dunn's test . 42
5.3.3.5 Mann-Whitney test. 43
5.3.4 Step-down trend procedures . 43
5.3.5 Determining the NOEC using a step-down procedure based on a trend test . 43
5.3.5.1 General . 43
5.3.5.2 Preliminaries . 43
5.3.5.3 Step-down procedure. 43
5.3.5.3.1 Preferred approach . 43
5.3.5.3.2 Williams' test. 44
5.3.5.3.3 Jonckheere-Terpstra test. 44
5.3.6 Assumptions for methods for determining NOEC values . 44
5.3.6.1 Small samples — Massive ties. 44
5.3.6.2 Normality . 45
5.3.6.3 Variance homogeneity . 45
5.3.7 Operational considerations for statistical analyses. 46
5.3.7.1 Treatment of experimental units. 46
5.3.7.2 Identification and meaning of outliers . 46
5.3.7.3 Multiple controls. 46
5.3.7.4 General . 47
5.4 Statistical items to be included in the study report. 47
6 Dose-response modelling . 48
6.1 Introduction . 48
6.2 Modelling quantal dose-response data (for a single exposure duration) . 49
6.2.1 General . 49
6.2.2 Choice of model . 50
iv © ISO 2006 – All rights reserved

---------------------- Page: 4 ----------------------
ISO/TS 20281:2006(E)
6.2.2.1 General .50
6.2.2.2 Probit model .51
6.2.2.3 Logit model.53
6.2.2.4 Weibull model.54
6.2.2.5 Multi-stage models.55
6.2.2.6 Definitions of EC and EC .55
50 x
6.2.3 Model fitting and estimation of parameters .56
6.2.3.1 Software and assumptions .56
6.2.3.2 Response in controls.56
6.2.3.3 Analysis of data with various observed fractions at each dose group.57
6.2.3.4 Analysis of data with one observed fraction at each dose group .58
6.2.3.5 Extrapolation and EC .58
x
6.2.3.6 Confidence intervals.58
6.2.4 Assumptions .59
6.2.4.1 General .59
6.2.4.2 Statistical assumptions .59
6.2.4.3 Evaluation of assumptions .59
6.2.4.3.1 Evaluation of basic assumptions .59
6.2.4.3.2 Evaluation of the additional assumption.59
6.2.4.4 Consequences of violating the assumptions.60
6.2.4.4.1 Consequences of violating basic assumptions.60
6.2.4.4.2 Consequences of violating the additional assumption .60
6.3 Dose-response modelling of continuous data (for a single exposure duration) .60
6.3.1 Purpose.60
6.3.2 Terms and notation.60
6.3.3 Choice of model.61
6.3.3.1 First distinctions .61
6.3.3.2 Linear models.62
6.3.3.3 Threshold models .62
6.3.3.4 Additive versus multiplicative models.63
6.3.3.5 Models based on “quantal” models.63
6.3.3.6 Nested non-linear models .64
6.3.3.7 Hill model .67
6.3.3.8 Non-monotone models .67
6.3.4 Model fitting and estimation of parameters .68
6.3.4.1 Software and assumptions .68
6.3.4.2 Response in controls.68
6.3.4.3 Fitting the model assuming normal variation .68
6.3.4.4 Fitting the model assuming normal variation after log-transformation .68
6.3.4.5 Fitting the model assuming normal variation after other transformations.69
6.3.4.6 No individual data available.69
6.3.4.7 Fitting the model using GLM.69
6.3.4.8 Covariates .70
6.3.4.9 Heterogeneity and weighted analysis.71
6.3.4.10 Confidence intervals.73
6.3.4.11 Extrapolation .73
6.3.4.12 Analysis of data with replicated dose group.73
6.3.5 Assumptions .74
6.3.5.1 General .74
6.3.5.2 Statistical assumptions .74
6.3.5.3 Additional assumption .74
6.3.6 Evaluation of assumptions .75
6.3.7 Consequences of violating the assumptions .75
6.3.7.1 Basic assumptions .75
6.3.7.2 Additional assumption .76
6.4 To accept or not accept the fitted model? .77
6.4.1 Can the fitted model be accepted and used for its intended purpose?.77
6.4.2 Is the model in agreement with the data? .77
6.4.3 Do the data provide sufficient information for fixing the model? .77
© ISO 2006 – All rights reserved v

---------------------- Page: 5 ----------------------
ISO/TS 20281:2006(E)
6.5 Design issues . 81
6.5.1 General . 81
6.5.2 Location of dose groups . 81
6.5.3 Number of replicates . 81
6.5.4 Balanced versus unbalanced designs.82
6.6 Exposure duration and time. 82
6.6.1 General . 82
6.6.2 Quantal data. 82
6.6.3 Continuous data. 83
6.6.3.1 General . 83
6.6.3.2 Independent observations in time . 83
6.6.3.3 Dependent observations in time. 85
6.7 Search algorithms and non-linear regression . 85
6.8 Reporting statistics. 86
6.8.1 Quantal data. 86
6.8.2 Continuous data. 87
7 Biology-based methods . 87
7.1 Introduction . 87
7.1.1 Effects as functions of concentration and exposure time. 87
7.1.2 Parameter estimation. 89
7.1.3 Outlook. 89
7.2 Modules of effect-models. 90
7.2.1 General . 90
7.2.2 Toxico-kinetic model .
...

SLOVENSKI STANDARD
SIST-TS ISO/TS 20281:2010
01-september-2010
.DNRYRVWYRGH1DYRGLOR]DVWDWLVWLþQRLQWHUSUHWDFLMRHNRWRNVLNRORãNLKSRGDWNRY
Water quality - Guidance on statistical interpretation of ecotoxicity data
Qualité de l'eau - Lignes directrices relatives à l'interprétation statistique de données
écotoxicologiques
Ta slovenski standard je istoveten z: ISO/TS 20281:2006
ICS:
13.060.70 Preiskava bioloških lastnosti Examination of biological
vode properties of water
SIST-TS ISO/TS 20281:2010 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

---------------------- Page: 1 ----------------------

SIST-TS ISO/TS 20281:2010

---------------------- Page: 2 ----------------------

SIST-TS ISO/TS 20281:2010


TECHNICAL ISO/TS
SPECIFICATION 20281
First edition
2006-04-01

Water quality — Guidance on statistical
interpretation of ecotoxicity data
Qualité de l'eau — Lignes directrices relatives à l'interprétation
statistique de données écotoxicologiques




Reference number
ISO/TS 20281:2006(E)
©
ISO 2006

---------------------- Page: 3 ----------------------

SIST-TS ISO/TS 20281:2010
ISO/TS 20281:2006(E)
PDF disclaimer
This PDF file may contain embedded typefaces. In accordance with Adobe's licensing policy, this file may be printed or viewed but
shall not be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In
downloading this file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat
accepts no liability in this area.
Adobe is a trademark of Adobe Systems Incorporated.
Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation
parameters were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In
the unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given below.


©  ISO 2006
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,
electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or
ISO's member body in the country of the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
Web www.iso.org
Published in Switzerland

ii © ISO 2006 – All rights reserved

---------------------- Page: 4 ----------------------

SIST-TS ISO/TS 20281:2010
ISO/TS 20281:2006(E)
Contents Page
Foreword.xii
Introduction .xiii
1 Scope .1
2 Normative references .1
3 Terms and definitions .1
4 General statistical principles.8
4.1 Different statistical approaches .8
4.1.1 General.8
4.1.2 Hypothesis-testing methods .8
4.1.3 Concentration-response modelling methods .10
4.1.4 Biology-based methods .11
4.2 Experimental design issues .11
4.2.1 General.11
4.2.2 NOEC or EC : Implications for design.12
x
4.2.3 Randomization .12
4.2.4 Replication.13
4.2.5 Multiple controls included in the experimental design.13
4.3 Process of data analysis.14
4.3.1 General.14
4.3.2 Data inspection and outliers.14
4.3.3 Data inspection and assumptions .15
4.3.3.1 Scatter .15
4.3.3.2 Heterogeneous variances and distribution .15
4.3.3.3 Heterogeneous variances and true variation in response.16
4.3.3.4 Consequences for the analysis .16
4.3.4 Transformation of data.16
4.3.5 Parametric and non-parametric methods .17
4.3.5.1 General .17
4.3.5.2 Parametric methods.17
4.3.5.3 Generalized linear models (GLMs) .18
4.3.5.4 Non-parametric methods.18
4.3.5.5 How to choose?.18
4.3.6 Pre-treatment of data.19
4.3.7 Model fitting.19
4.3.8 Model checking.20
4.3.8.1 Analysis of residuals .20
4.3.8.2 Validation of fitted dose-response model .21
4.3.9 Reporting the results.21
5 Hypothesis testing.21
5.1 Introduction.21
5.1.1 General.21
5.1.2 NOEC: What it is, and what it is not.25
5.1.3 Hypothesis used to determine NOEC.25
5.1.3.1 Understanding the question to be answered .25
5.1.3.2 One-sided hypothesis.26
5.1.3.3 Two-sided trend test .26
5.1.3.4 Trend or pair-wise test.26
5.1.4 Comparisons of single-step (pair-wise comparisons) or step-down trend tests to
determine the NOEC.28
© ISO 2006 – All rights reserved iii

---------------------- Page: 5 ----------------------

SIST-TS ISO/TS 20281:2010
ISO/TS 20281:2006(E)
5.1.4.1 General discussion . 28
5.1.4.2 Single-step procedures. 28
5.1.4.3 Step-down procedures. 29
5.1.4.4 Deciding between the two approaches . 30
5.1.5 Dose metric in trend tests . 31
5.1.6 Role of power in toxicity experiments . 31
5.1.7 Experimental design . 32
5.1.8 Treatment of covariates and other adjustments to analysis. 33
5.2 Quantal data (e.g. mortality, survival). 34
5.2.1 Hypothesis testing with quantal data to determine NOEC values . 34
5.2.2 Parametric versus non-parametric tests .35
5.2.2.1 Basis . 35
5.2.2.2 Single-step procedures. 36
5.2.2.3 Step-down procedures. 36
5.2.2.3.1 Choice of step-down procedure. 36
5.2.2.3.2 Test for monotone dose response . 36
5.2.2.3.3 Analysing the monotonic response for quantal data — Step-down procedure . 37
5.2.2.3.4 Possible modifications of the step-down procedure. 37
5.2.2.4 Alternative procedures . 37
5.2.2.4.1 Parametric and non-parametric procedures. 37
5.2.2.4.2 Pair-wise ANOVA-based methods . 38
5.2.2.4.3 Jonckheere-Terpstra trend test.38
5.2.2.4.4 Poisson tests . 38
5.2.2.5 Assumptions of methods for determining NOEC values . 38
5.2.3 Additional information. 39
5.2.4 Statistical items to be included in the study report. 40
5.3 Hypothesis testing with continuous data (e.g. mass, length, growth rate) to determine
NOEC . 40
5.3.1 General . 40
5.3.2 Parametric versus non-parametric tests .41
5.3.3 Single-step (pair-wise) procedures . 42
5.3.3.1 General . 42
5.3.3.2 Dunnett's test. 42
5.3.3.3 Tamhane-Dunnett test. 42
5.3.3.4 Dunn's test . 42
5.3.3.5 Mann-Whitney test. 43
5.3.4 Step-down trend procedures . 43
5.3.5 Determining the NOEC using a step-down procedure based on a trend test . 43
5.3.5.1 General . 43
5.3.5.2 Preliminaries . 43
5.3.5.3 Step-down procedure. 43
5.3.5.3.1 Preferred approach . 43
5.3.5.3.2 Williams' test. 44
5.3.5.3.3 Jonckheere-Terpstra test. 44
5.3.6 Assumptions for methods for determining NOEC values . 44
5.3.6.1 Small samples — Massive ties. 44
5.3.6.2 Normality . 45
5.3.6.3 Variance homogeneity . 45
5.3.7 Operational considerations for statistical analyses. 46
5.3.7.1 Treatment of experimental units. 46
5.3.7.2 Identification and meaning of outliers . 46
5.3.7.3 Multiple controls. 46
5.3.7.4 General . 47
5.4 Statistical items to be included in the study report. 47
6 Dose-response modelling . 48
6.1 Introduction . 48
6.2 Modelling quantal dose-response data (for a single exposure duration) . 49
6.2.1 General . 49
6.2.2 Choice of model . 50
iv © ISO 2006 – All rights reserved

---------------------- Page: 6 ----------------------

SIST-TS ISO/TS 20281:2010
ISO/TS 20281:2006(E)
6.2.2.1 General .50
6.2.2.2 Probit model .51
6.2.2.3 Logit model.53
6.2.2.4 Weibull model.54
6.2.2.5 Multi-stage models.55
6.2.2.6 Definitions of EC and EC .55
50 x
6.2.3 Model fitting and estimation of parameters .56
6.2.3.1 Software and assumptions .56
6.2.3.2 Response in controls.56
6.2.3.3 Analysis of data with various observed fractions at each dose group.57
6.2.3.4 Analysis of data with one observed fraction at each dose group .58
6.2.3.5 Extrapolation and EC .58
x
6.2.3.6 Confidence intervals.58
6.2.4 Assumptions .59
6.2.4.1 General .59
6.2.4.2 Statistical assumptions .59
6.2.4.3 Evaluation of assumptions .59
6.2.4.3.1 Evaluation of basic assumptions .59
6.2.4.3.2 Evaluation of the additional assumption.59
6.2.4.4 Consequences of violating the assumptions.60
6.2.4.4.1 Consequences of violating basic assumptions.60
6.2.4.4.2 Consequences of violating the additional assumption .60
6.3 Dose-response modelling of continuous data (for a single exposure duration) .60
6.3.1 Purpose.60
6.3.2 Terms and notation.60
6.3.3 Choice of model.61
6.3.3.1 First distinctions .61
6.3.3.2 Linear models.62
6.3.3.3 Threshold models .62
6.3.3.4 Additive versus multiplicative models.63
6.3.3.5 Models based on “quantal” models.63
6.3.3.6 Nested non-linear models .64
6.3.3.7 Hill model .67
6.3.3.8 Non-monotone models .67
6.3.4 Model fitting and estimation of parameters .68
6.3.4.1 Software and assumptions .68
6.3.4.2 Response in controls.68
6.3.4.3 Fitting the model assuming normal variation .68
6.3.4.4 Fitting the model assuming normal variation after log-transformation .68
6.3.4.5 Fitting the model assuming normal variation after other transformations.69
6.3.4.6 No individual data available.69
6.3.4.7 Fitting the model using GLM.69
6.3.4.8 Covariates .70
6.3.4.9 Heterogeneity and weighted analysis.71
6.3.4.10 Confidence intervals.73
6.3.4.11 Extrapolation .73
6.3.4.12 Analysis of data with replicated dose group.73
6.3.5 Assumptions .74
6.3.5.1 General .74
6.3.5.2 Statistical assumptions .74
6.3.5.3 Additional assumption .74
6.3.6 Evaluation of assumptions .75
6.3.7 Consequences of violating the assumptions .75
6.3.7.1 Basic assumptions .75
6.3.7.2 Additional assumption .76
6.4 To accept or not accept the fitted model? .77
6.4.1 Can the fitted model be accepted and used for its intended purpose?.77
6.4.2 Is the model in agreement with the data? .77
6.4.3 Do the data provide sufficient information for fixing the model? .77
© ISO 2006 – All rights reserved v

---------------------- Page: 7 ----------------------

SIST-TS ISO/TS 20281:2010
ISO/TS 20281:2006(E)
6.5 Design issues . 81
6.5.1 General . 81
6.5.2 Location of dose groups . 81
6.5.3 Number of replicates . 81
6.5.4 Balanced versus unbalanced designs.82
6.6 Exposure duration and time. 82
6.6.1 General . 82
6.6.2 Quantal data. 82
6.6.3 Continuous data. 83
6.6.3.1 General . 83
6.6.3.2 Independent observations in time . 83
6.6.3.3 Dependent observations in time. 85
6.7 Search algorithms and non-linear regression . 85
6.8 Reporting statistics. 86
6.8.1 Quantal data. 86
6.8.2 Continuous data. 87
7 Biology-based methods . 87
7.1 Introduction .
...

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