Appendix A: Glossary

(1)

Appendix A: Glossary

ACP Acid phosphatase

ACRP Association of Clinical Research Professionals (http://www.acrpnet.org/) ACV% Annualized coefficient of variation

ADR Adverse drug reaction

AE Adverse event

ALP Alkaline phosphatase ANOVA Analysis of variance AP Antero-posterior

ASIS Anterior superior iliac spine BALP Bone-specific alkaline phosphatase BMC Bone mineral content in grammes

BMD Bone mineral density in grammes per square centimetre. Calculated as the bone mineral content of a bone divided by the area of the bone and as such it is not true density

BMI Body-mass index

BMP Bone morphogenic proteins

BUA Broadband ultrasound attenuation measured in decibels per megahertz (dB MHz

^⫺1

); a measure of the attenuation of ultrasound through the heel CLIA Clinical Laboratory Improvement Amendments. An accrediting body for lab-

oratories in the USA (http://www.clianet.org) COREC Central Office of Research Ethics Committees

CPA Clinical Pathology Accreditation. An accrediting body for laboratories in the UK (http://www.cpa-uk.demon.co.uk/index.htm)

CPMP The Committee for Proprietary Medicinal Products. The European Committee responsible for reviewing standards for Good Clinical Practice

CRA Clinical research associate. A representative of a CRO responsible for liaison between the CRO and sites participating in the trial

CRO Clinical research organization. A company responsible for administering the trial on behalf of a sponsor

CT Computed tomography

CTA Clinical trial agreement on study consent CTx C-terminal telopeptide or crosslaps CUSUM Cumulative sum charts

CV Curriculum vitae CV, CV% Coefficient of variation DPyd Deoxypridinoline

DSMC Data Safety Monitoring Committee

DXA Dual-energy X-ray absorptiometry. The principal technique used for measur- ing BMD

ED Effective dose measured in millisieverts (mSv). A measure of radiation dose that can be related directly to the risk of the radiation exposure

ELISA Enzyme-linked immunosorbent assay

279

(2)

EQA External quality assurance

ESD Entrance skin dose measured in milligrays (mGy) ESP European spine phantom

FDA US Food and Drug Administration. The US agency responsible for the licensing of pharmaceuticals. A good source of guidelines on the conduct of clinical trials is their website http://www.fda.gov/

GCP Good clinical practice. The international standard for conduct of clinical trials

GHyL Galactosyl hydroxylysine GLP Good laboratory practice

GP General practitioner or primary care physician

GREES The Group for the Respect of Ethics and Excellence in Science HPLC High-performance liquid chromatography

HRT Hormone-replacement therapy or oestrogen-replacement therapy

ICH International Committee on Harmonization. Produces international standards for the conduct of clinical trials (http://www.ifpma.org/ich1.html)

ICP-MS Inductively coupled plasma mass spectrometry

ICR Institute of Clinical Research (http://www/instituteofclinicalresearch.org/) ICTP Type I collagen C-terminal telopeptide

IDSC International DXA Standardization Committee IND Investigational new drug

IQC Internal quality control

IRB/IEC Institutional Review Board or Independent Ethics Committee responsible for reviewing and approving the ethical basis of the trial at each participating center

IRMA Immunoradiometric assay

ISCD International Society for Clinical Densitometry (http://www.iscd.org/) ISO International Standards Organization (http://www.iso.ch/iso/en/ISOOnline.

openerpage)

MRI Magnetic resonance imaging

MXA Morphometric X-ray analysis. A technique from radiographers for lateral scans of the spine using DXA that measures the height of vertebra, allowing the identification of vertebral fractures

NEQAS UK National External Quality Assessment Schemes (http://www.ukneqas.

org.uk/)

NHANES The National Health and Nutrition Examination Survey; a survey conducted by the National Center for Health Statistics, part of the Centers for Disease Control and Prevention, US Public Health Service. This survey has been designed to collect information about the health and diet of people in the USA. NHANES is unique in that it combines a home interview with health tests. The tests included measuring BMD at the femur (http://www.cdc.gov/

nchs/nhanes.htm)

NIBSC National Institute for Biological Standards and Control (http://www/nibsc.

ac.uk)

NIH National Institutes of Health. An American agency who commission and fund health research. They have produced consensus guidelines on osteo- porosis (http://www.nih.gov/)

NIST National Institute of Standards and Technology (http://www.nist.gov/)

280 Appendix A: Glossary

(3)

NME New molecular entity. A new drug under development being tested in a clinical trial

NNT Number needed to treat (to prevent one fracture)

NOF National Osteoporosis Foundation (USA) (http://www/nof.org/) NOS National Osteoporosis Society (UK) (http://www/nos.org.uk/) NTx N-terminal telopeptide-linked crosslink

OA Osteoarthritis

OHP Hydroxyproline

PA Postero-anterior

PDXA Peripheral DXA measures BMD of forearm or heel PQCT Peripheral QCT—usually measures BMD of the forearm

PTH Parathyroid hormone

Pyd Pyridinoline

QA Quality assurance. Review of the quality control information by sam- pling or audit

QC Quality control. The ongoing sampling of a process to ensure that the quality of the process is within defined limits. For example, daily phan- tom measurements on DXA equipment

QCT Quantitative computed tomography. A method of measuring bone den- sity from a CT scan

QUALEFFO Quality of Life Questionnaire of the European Foundation of Osteoporosis QUS Quantitative ultrasound. A technique that measures the attenuation of ultrasound (BUA) through the heel and the velocity or speed of sound (VOS or SOS). These measures are often combined to calculate the stiff- ness or Stiffness Index

RCT Randomized, controlled trial

RIA Radioimmunoassay

RIQAS Randox International Quality Assessment Scheme (http://www.randox.

com/riqas.htm)

RMS SD Root mean squared standard deviation ROC Receiver operating characteristics

ROI Region of interest. Area set on image to calculate BMD SADR Serious adverse drug reaction

SAE Serious adverse event

sBMD Standardized BMD in milligrammes per square centimetre SCV% Standardized coefficient of variation

SD Standard deviation

SEE Standard error of estimate

SERM Selective oestrogen receptor modulator SF-36 A validated health status questionnaire

SMO Site management organization. A local research organization or hospital that recruits subjects and carries out the clinical trial on behalf of a CRO SOCRA Society of Clinical Research Associates (http://www.socra.org/) SOP Standard operating procedure

SOS Speed of sound (ms

^⫺1

) measured using QUS in the heel SSC Study site coordinator

SSE Residual sum of squares TALP Total alkaline phosphatase

Appendix A: Glossary 281

(4)

tns gene Tissue nonspecific gene

TRACP Tartrate resistant acid phosphatase

VOS Velocity of sound (ms

^⫺1

) measured using QUS in the heel WEQAS Wales External Assessment Scheme

WHO World Health Organization (http://www.who.int/)

282 Appendix A: Glossary

(5)

Appendix B: Sample Data

from the Example Study Used in this Book

See table that begins overleaf.

(6)

284 Appendix B: Sample Data

The BMD measur emen ts for the AP spine ar e sho wn in g/cm

2

.T he BU A is in dB MHz

⫺1

.T her e ar e missing v alues in the BU A da ta because of equipmen t failur e. Gr oup 1 is the plac ebo-tr ea te d gr oup and Gr oup 2 is the ac tiv e tr ea tmen t gr oup .T her e is additional demogr aphic informa tion, such as age ,c en tr e, and smoking habi ts. Smoking is c oded as 1 ⫽ nonsmok er and 2 ⫽ smok er . Baseline BMD BMD BMD BMD Baseline B U A B U A B U A B U A Age BMD 1 y ear 2 y ears 3 y ears 4 y ears B U A 1 y ear 2 y ears 3 y ears 4 y ears Group Centre Smoking 50 1.246 1.285 1.285 1.325 1.325 2 1 2 48 0.98 0.966 1.01 1.033 1.015 2 2 2 48 1.068 1.081 1.052 1.076 1.09 115 114 110 108 104 2 1 2 49 0.956 0.964 0.973 0.988 1.013 119 118 117 118 119 2 2 1 52 1.001 1.019 1.051 1.087 1.093 99.1 95 96 98 99 2 1 2 57 0.844 0.866 0.886 0.909 0.912 111.5 107 114 115 112 2 2 2 50 0.825 0.927 0.908 0.948 0.979 118.7 124 122 125 130 2 1 2 51 1.108 1.129 1.128 1.14 1.125 140.5 137 141 140 139 2 2 1 45 1.053 1.069 1.042 1.12 1.098 106.9 107 108 107 106 2 1 1 57 0.861 0.895 0.929 0.977 0.936 110.9 110 108 107 108 2 2 2 51 1.018 1.026 1.038 1.041 1.053 116.5 129 120 116 118 2 1 2 58 0.883 0.904 0.912 0.961 0.972 134 128 124 120 121 2 2 1 51 0.961 0.96 0.991 1.022 1.022 105.2 101 2 1 2 50 0.911 0.983 1.013 1.018 1.015 120.5 121 122 123 118 2 2 2 53 0.911 0.926 0.938 0.942 0.944 132 137 130 125 120 2 1 1 52 0.952 1.02 0.97 1.053 1.031 114 111 113 111 110 2 2 2 52 1.068 1.078 1.134 1.142 1.148 120 120 120 121 118 2 1 2 52 0.856 0.875 0.89 0.912 0.902 104.4 103 102 101 99 2 2 1 51 0.808 0.82 0.793 0.8 0.811 145 125 125 127 129 2 1 2 56 0.927 0.965 0.968 0.985 1.017 125 121 114 110 110 2 2 1 53 1.185 1.235 1.236 1.297 1.338 112.3 112 110 108 111.2 2 1 1 54 1.005 1.062 1.056 1.096 1.084 125 125 124 123 122 2 2 1 56 0.73 0.817 0.818 0.819 0.823 111.1 117 114 113 112 2 1 1 49 0.789 0.814 0.814 0.839 0.839 101 99 2 2 1 50 1.019 1.059 1.068 1.11 1.105 110 107 109 105 113 2 1 2 48 0.974 0.986 0.969 1.006 1.016 114 112 114 114 112 2 2 1 47 0.974 1.028 0.979 1.031 1.021 119 114 116 118 118 2 1 2

(7)

Appendix B: Sample Data 285

59 0.778 0.836 0.844 0.853 0.874 106.5 106 105 105 106 2 2 1 58 0.887 0.95 0.951 0.973 0.959 105.6 110 113 110 115 2 1 1 49 0.854 0.917 0.946 0.916 0.943 103.2 106 106 99 103 2 2 2 56 0.735 0.737 0.711 0.68 0.689 99.7 95 96 92 91.6 1 1 1 50 0.789 0.728 0.697 0.685 0.68 120 113 115 114 101 1 2 2 55 0.797 0.783 0.774 0.767 0.762 107 105 89 94 101 1 1 2 50 0.803 0.793 0.764 0.758 0.722 109.8 104 96 101 106 1 2 2 45 0.822 0.781 0.823 0.84 0.813 110.8 109 101 101 103 1 1 2 48 0.829 0.833 0.839 0.811 0.809 108 105 100 101 90 1 2 1 53 0.83 0.825 0.81 0.773 0.854 115 110 112 106 109 1 1 1 51 0.861 0.861 0.835 0.858 0.876 113.2 113 110 107 91 1 2 2 54 0.884 0.856 0.836 0.845 0.826 107 106 101 100 109 1 1 1 53 0.905 0.921 0.922 0.955 0.931 109 108 104 102 101 1 2 2 50 0.907 0.864 0.877 0.867 0.888 140 135 106 101 101 1 1 1 57 0.935 0.923 0.912 0.911 0.908 112 109 114 112 110 1 2 1 53 0.913 0.898 0.895 0.887 0.924 106.8 105 101 90 103 1 1 2 50 0.926 0.941 0.876 0.861 0.855 111.1 109 113 110 111 1 2 1 52 0.943 0.912 0.897 0.941 0.945 110.8 113 109 112 116 1 1 2 55 0.967 0.933 0.94 0.943 0.927 1 2 2 58 0.976 0.95 0.965 0.963 0.955 109.9 105 106 105 99 1 1 1 49 0.975 0.969 0.969 0.973 1.013 135 132 129 131 123 1 2 2 55 0.952 0.94 0.926 0.938 0.917 103.4 97 100 97 89.9 1 1 1 47 0.988 0.966 0.895 0.901 0.889 110 107 104 97 103 1 2 1 50 0.996 0.93 0.921 0.918 0.936 124.8 109 119 115 114.9 1 1 2 51 1.004 1.017 0.969 1.002 0.969 120.5 123 118 115 117 1 2 1 47 1.01 0.972 0.948 0.923 0.886 110.1 109 110 109 104 1 1 2 48 1.036 1.036 1 1.016 0.974 114.3 111 109 100 108 1 2 2 53 1.056 1.109 1.042 1.071 1.06 110 102 104 103 101 1 1 1 49 1.06 1.025 0.982 0.97 0.927 106 105 97 93 98 1 2 1 49 1.068 1.017 0.978 1.022 1.002 119 116 121 115 111 1 1 1 54 1.08 1.069 1.07 1.085 1.099 125.8 126 118 104 123 1 2 1 52 1.116 1.073 1.051 1.045 1.091 120 114 114 1 1 2 54 1.163 1.169 1.141 1.102 1.102 1 2 2

(8)

Abstract 164, 166–168, 185

Accuracy 57–59, 83, 99, 101, 103, 106, 131, 139, 154, 155–156, 157, 166, 238–239, 244, 256, 258

Acid phosphatase 248, 254 Ad Hoc Working Group for Critical

Appraisal of the Medical Literature 166

Adverse events 99, 101, 167, 168, 170, 184–185, 192, 193, 197, 198, 225–226, 227, 228

Alendronate 10, 185, 195–196, 197–198, 217, 218, 222, 224, 226, 227, 228, 272

Alkaline phosphatase 157, 254–257 Anabolic therapy 17, 192, 200, 215, 216,

217, 218, 219, 228, 240 Annualized precision 61

ANOVA 169, 174, 176, 178, 179, 180, 181, 182

Antiresorptive therapy 9, 17, 75, 194, 200, 212, 213, 214, 215, 216, 217, 219, 221, 224, 228, 240, 253, 273 Artefacts 17, 22, 105, 106, 110,

116, 119–120, 124, 125, 127, 128, 129, 240

Audit 3, 20, 80, 82, 85, 86–87, 88, 99, 100, 104, 134, 136–138, 141, 153

Bias 8, 12, 14, 17, 18, 23, 30, 58, 163, 165, 166, 168, 170, 171, 172 nonsignificant findings 167 peer review 38, 39 recruitment 20, 31 vertebral morphometry 80 Biochemical markers 32, 78, 80, 190,

216, 247 as endpoints 12

laboratory

Bisphosphonates 9, 13, 17–18, 29, 30,

78, 194–199, 203, 217, 218, 222, 224–225, 227, 228, 253, 261–262, 272, 275, 276, 277

Bland and Altman plot 48

Blinding 9, 10, 20, 85, 96, 101, 164, 170–171

Bona Fide phantom 51–52, 53, 54, 83, 142

Bone formation, markers of 141, 216, 248, 250, 261, 262

Bone formation agents 200, 212–216, 224, 228, 254, 255, 257–258 Bone gain 212–216, 228

clinical significance of 217–218 distribution within skeleton 221–222 Bone loss 77, 197, 200, 201, 211,

212, 213, 222, 224, 228, 247, 272–273, 276

age-related 59, 240

calcitonin 3, 14, 29, 166, 167, 168, 169, 204

HRT 192–193

Bone mineral density (BMD) 1, 2, 3, 8, 10, 12, 28, 47, 50, 76, 77, 78, 83, 88, 142, 163, 189, 197, 212, 220, 221, 235, 272, 275

assessment of 103, 168, 247 Bone morphogenic proteins 274 Bone remodelling 192, 193, 194, 203,

212, 214, 215, 218, 221, 224, 228 Bone resorption 155, 198, 213, 214, 215, 216, 217, 218, 224, 227, 249, 250, 251, 253, 254, 262

Bone-specific alkaline phosphatase 33, 157

Bonferroni method 174

Calcitonin 3, 9, 14, 29, 166, 167, 168, 169, 204, 216, 227, 275, 277 Calcitriol 203–204, 223, 227

Calcium supplements 38, 194, 201, 202 Case-controlled studies 8

287

Index

(9)

Centre effects 169, 172, 186 Chi-squared test 172, 184 Clinical trial agreement 93

Clinical trials 1, 3, 10, 17, 27, 48, 51, 59, 63, 103–138, 151–152, 163–165, 167–185, 213–214, 224, 225, 235–238, 240, 244, 271, 273–277

audit 86–87

case control study 8, 166 closure 88

cohort study 8, 28, 222, 239 cross-over trial 9, 164, 166 cross-sectional 7, 261 factorial design 9

local organization 48, 91–101 longitudinal 7, 8, 145, 164, 169,

177–182, 186, 262 organization 75–88

phases of 2, 7, 8, 9, 11, 12, 18, 28, 30, 31, 32, 67, 75, 76, 77, 218, 219, 222, 226, 241, 242, 272 prevention versus treatment 30, 76,

190, 194, 212, 221, 273 procedures 31–35, 36–39, 68 randomized, controlled 8–9, 10, 30,

46, 164, 165, 166, 167, 168, 189, 198, 199

Coefficient of variation 12, 50, 60, 154, 238, 239, 261

Cohort studies 8, 28

Collagen 200, 248, 249, 250, 251, 252, 253, 260

Committee for Proprietary Medicinal Products 27, 75

Compliance 9, 11, 17, 20, 60, 98–99, 136, 192, 200, 202, 205, 211, 216, 224–225

Confidence interval 164, 183, 184, 191, 193, 196, 262

CONSORT statement 164–166, 168, 185 Contact information 38, 138

Correspondence 87, 138 Couriers 81, 82, 95, 136

Crosscalibration 48, 51, 52, 53, 54, 55, 64–65, 85, 171

DXA 50–56, 82–84, 142–153 phantoms 47, 49, 50–56, 57, 60, 64, 82,

83, 84, 94, 96, 144–145, 152, 240

statistics 83–84

ultrasonometry 3, 8, 10, 11, 17, 31, 47, 50, 58, 62, 141, 152–153, 235, 236, 238, 239, 241

Crosslinks 248, 249–250, 251, 252, 253, 261

Cross-over trials 9, 164, 166

Cumulative sum charts (CUSUM) 145, 149–151

Data archive 133–134

Database 20, 31, 58, 84, 85, 96, 97, 106–107, 109, 134, 145, 148, 201, 239, 244

Data collection 7, 22–23, 78–80 Data flow 81, 85–86, 87

Data Monitoring Committee 101, 177 Declaration of Helsinki 2, 27, 29, 78 Deoxypyridinoline 157, 248, 249, 250 Didronel® 194

Discrimination 10, 239, 240 Dissemination 7, 18, 19, 38–39, 163 Documentation 18–20, 56, 58, 86, 87,

88, 93–95, 96, 98, 99, 100, 103, 135, 137, 138, 153, 169

Dose response 211, 218–221 Dual energy X-ray absorptiometry

see DXA

Duncan’s multiple range test 174 DXA 12, 17, 33, 37, 44, 59, 61, 62, 64,

65, 67, 78, 84, 94, 95, 96, 101, 104, 106, 108, 139, 182, 216, 236, 241 contraindications 42, 105

equipment differences 11, 34, 35, 47, 48–50

equipment replacement 152–153 femur 11, 32, 34, 103, 120–127, 167,

168, 242, 244

forearm 34, 103, 127–130, 242 lumbar spine 3, 34, 35, 41, 63, 64, 66,

103, 107, 112–114, 115, 116, 117, 119, 131, 167, 168, 177, 238, 239, 240, 242, 244

MXA 3, 11, 67, 68, 103, 130–133, 237 phantoms 50–57, 83

quality assurance 79, 80, 81, 82, 83, 85, 87, 103, 112, 120, 130, 134, 135, 136, 137, 157–158, 235, 240

288 Index

(10)

quality control 22, 137, 138, 141–153, 171

scan acquisition 109–112 scan analysis 110–111, 247 scan mode 115–116

Effective dose 32, 34, 35, 67, 218, 219 Effectiveness 7, 8, 9, 29, 41, 163, 189,

194, 195, 196, 198, 199, 201 Efficacy 8, 9, 19, 29, 78, 80, 82, 191,

192, 194, 195, 197, 200, 201, 223, 225, 227–228, 273, 277

Electrophoresis 254, 255–256, 257 Endpoints 2, 3, 10–12, 13–14, 17, 19, 22,

31, 32, 50, 58, 76, 77, 78, 83, 85, 88, 163, 197, 203, 220, 221, 224, 226, 228, 244, 275

evaluation 235–243

fracture risk Entrance skin dose 32, 67

Enzyme-linked immunosorbent assay (ELISA) 251, 253, 256, 257 Equipment differences

DXA 48–50 ultrasound 50

Equipment replacement 152–153 Equivalence trials 14–16

Errors 49, 50, 62, 65, 75, 84, 88, 93, 107, 111, 142, 146, 148, 150, 151, 152, 153, 169, 172, 174, 178, 236 DXA acquisition 109–112 type I and II 13, 14, 15, 169 Ethical review 30, 35–36

Etidronate 191, 194–195, 215, 218, 227, 228

European spine phantom 51, 53, 69, 83, 142

Exclusion criteria 7, 17–18, 19, 30, 31, 57, 76, 84–85, 86, 105, 164, 167, 169

Falls 53, 54, 189, 201, 202, 203, 204, 216, 257, 276

Femur DXA 11, 32, 34, 103, 120–121, 167, 168, 242, 244

image analysis 125–127 image review 110, 112, 124–125 scan mode selection 124 scanner preparation 123

subject positioning 22, 105, 106, 109–110, 122–123, 125, 139 Fisher’s exact test 172

Fluoride 217, 222, 228

Food and Drug Administration (FDA) 11, 28, 242, 272

adverse event definition 225

clinical trials guidelines 9–10, 54, 241 documentation 27, 88, 93–94, 100 ethical guidelines 2, 27, 28, 31,

36, 37

good practice guidelines 75–77, 78 placebo control trials 2, 29–30, 225 preferred phantoms 54, 142 trial audit 86–87

Forearm DXA

image analysis 125–127, 129–130 image review 110, 111–112, 124–125,

128–129

scan mode selection 128 subject positioning 22, 105, 106,

109–110, 127–128, 139 Fosamax

^®

195, 197, 272, 276 Fracture

appendicular 221, 224, 273, 274–275 as endpoint 11, 12

vertebral 3, 10, 12, 13, 58, 68, 103, 104, 106, 130, 131, 133, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 203, 204, 206, 217, 220, 221, 223, 225, 237, 240, 273–274 Fracture Intervention Trial 25, 185, 195,

196, 226

Fracture risk 2, 11, 28, 58, 130, 163, 166, 167, 184–185, 189–190, 191, 192, 197, 204, 240, 275

effect on study design 13, 38, 201

Galactosyl hydroxylysine 248, 249, 250 Genetic testing 35, 275

Good clinical practice (GCP) 18, 19, 27, 30, 38, 75, 99, 100, 136, 139 Group for the Respect of Ethics and

Excellence in Science 76, 77

Health-outcome questionnaires 12 High-performance liquid chromatography

249, 251

Hologic hip phantom 49, 55

Index 289

(11)

Hologic spine phantom 51, 52, 53, 104, 144, 148, 151

Hormone-replacement therapy (HRT) 18, 30, 64, 189, 193, 215, 227 BMD 10, 217

bone loss prevention 192, 212, 222 bone mass increase 212

clinical trial subject information 226, 227, 252, 253, 262, 271

compliance with 17, 217

reasons for not taking 30, 226, 271 safety and tolerability 226–227 treatment effect 30

Hydroxyproline 248–249

ICH Guidelines on Good Clinical Practice 18, 27, 99

Immunoassay 252, 253, 256–257, 259 Inclusion criteria 17–18, 19, 23, 58, 98,

165, 168, 169

Independent Review Board/Independent Ethics Committee see IRB/IEC Informed consent 3, 18, 27, 31, 32, 35,

36–38, 99, 171

Intention-to-treat analysis 164, 169–170 Interim analysis 21, 86

Investigator meetings 81–82

IRB/IEC 20, 27, 31, 32, 35, 36, 39, 97, 101, 102, 171, 243

approval 38, 92, 94, 95, 98 review 94–95

submission 92, 93

Kruskal–Wallis test 169, 183 Kurtosis 172

Laboratory 22, 79, 80, 81, 82, 88, 91, 94, 95, 99, 100, 141–152, 155

accreditation 153

external quality assurance (EQA) 87, 157–158

internal quality control (IQC) 154, 156–157

Linear regression 62, 66, 145–146, 151 Longitudinal data 145, 164, 168, 169,

177–182, 187 Lumbar spine DXA

image analysis 116–120 image review 110, 111–112, 116

scan mode selection 115–116 scanner preparation 114–115 subject positioning 22, 105, 106,

109–110, 112–114, 117, 139 Lunar aluminium spine phantom 51, 53,

147, 151

Male osteoporosis 196, 228, 272, 275 Missing values 169–170, 284

Monitoring 2, 3, 8, 11, 17, 33, 35, 58, 62, 184, 204, 216, 235, 240, 241, 248, 259, 261

clinical trial 9, 19, 20, 47, 57, 61, 63, 75, 86, 88, 98, 99–100, 101, 143, 144, 168, 177, 178, 236, 242 quality control 19, 56, 85, 103, 136,

143, 145, 156–157

Morphometric absorptiometry see MXA Morphometry 69, 85, 87, 235, 237, 249

vertebral, 11, 67, 78, 80–81, 131, 235, 243

Moving average 145, 146–147 Multiple range tests 174

MXA 3, 11, 67, 68, 103, 130, 237 scan acquisition 131, 134 scan analysis 131–133 subject positioning 131

Nonparametric statistics 172, 174, 182–183

Normal ranges 58, 59, 61, 85, 94, 236, 237, 262

MXA 68

Normal scores 173, 175 Numbers needed to treat 223

Oestrogen see Hormone-replacement therapy

Osteoblasts/osteoblastic 192, 199, 200, 214, 215, 216, 224, 228, 247, 254, 257

Osteocalcin 33, 155, 157, 158, 248, 257–259, 261, 262

Osteoclasts/osteoclastic 192, 200, 214, 215, 216, 225, 247, 249, 251, 253, 254, 257

Osteoporosis definition 1–3

male 196, 228, 272, 275

290 Index

(12)

related diseases 272–273

treatment efficacy 8, 28, 30, 168, 191, 192, 194, 195, 197, 201, 227–228, 273, 277

Pamidronate 253

Parathyroid hormone 9, 75, 135, 199–200, 212, 213, 271 Peptide-linked crosslinks 249, 250,

252–253

Phantoms 47, 49–69, 82–84, 92, 94, 96, 104, 142–152, 240

ultrasound 56–57

Placebo 2, 3, 8, 9, 10, 13, 14, 16, 28–30, 38, 41, 42, 46, 64, 78, 101, 165, 166, 167, 168, 169, 178, 185, 193, 194, 195, 196, 197, 198, 199, 200, 203, 219, 221, 223, 224, 225, 226, 227, 236, 277, 284

Positioning 3, 22, 105, 106, 109, 110, 112, 139, 148, 243

femur 121–123, 124, 125 forearm 127–128, 129

lumbar spine 112–114, 116, 117 MXA 68, 130, 131

Power 7, 12–17, 86, 166, 201, 205, 238 Precision 47, 59–60, 62–64, 80, 83, 103,

110, 122, 150, 154–155, 238–239, 240, 244, 249, 255, 256, 262 annualized precision 61 standardized precision 61 Procollagen propeptides 260–261 Protocol 18–20, 23, 27, 28, 31, 39, 44,

68, 79, 86, 88, 92, 93, 94, 96, 99, 103, 107, 109, 110, 111, 113, 136, 164, 168, 251

Pyridinoline 248, 249, 250

Qualitative methods 23 Quality assurance 3, 19, 56, 78,

103–139, 141, 143, 235, 236 Quality assurance centres 57, 60, 61, 64,

65, 67, 68, 79, 81, 83, 85, 87, 103, 134, 151

Quality control 2, 3, 19, 47–69, 103, 104, 145–152, 236, 256

biochemistry 87, 141, 153–158 DXA 22, 138, 142–144, 158, 171 managing QC failure 151–152, 171

monitoring 3, 145, 146, 148, 150 QUS 3, 11, 33, 47, 58, 59, 63, 64, 65,

142, 144, 167, 168, 242 Quality of life 12, 22, 190

Quantitative computed tomography (QCT) 17, 32, 34, 51, 65, 105, 235, 236, 239, 241, 242

Quantitative ultrasound (QUS) 3, 11, 33, 47, 58, 59, 63, 64, 65, 142, 144, 167, 168, 242

Questionnaires 10, 11, 12, 22, 33

Radiation dose 32, 35, 44, 47, 67, 109, 110, 115, 241, 243

Radiographic vertebral morphometry 67 Radioimmunoassay 155, 251

Raloxifene 28, 191, 193, 194, 200, 201, 203, 215, 217, 218, 219, 221, 223, 226, 227

Randomization 19, 20–22, 30, 96, 107, 169, 170–171, 205, 224

Randomized, controlled trials 8–9, 30, 165 Receiver operating characteristic 105 Record keeping 19, 104, 136–138 Recruitment 16, 20, 21, 30, 38, 76, 80,

83, 85, 88, 91, 92, 96–98, 101, 168, 226, 257

Reference data see Normal ranges Regulatory guidelines 3, 10, 11, 18, 19,

20, 28, 29, 31, 37, 44, 75–78, 93–94, 100, 101, 201, 236, 241, 244, 277 Relevance 10, 14, 15, 16, 22, 103, 109,

111, 134, 135, 136, 138, 154, 169, 199, 211, 222, 227, 235, 236, 240, 242, 244 Reliability 11, 22, 60, 97, 152, 155, 216,

235, 239–240, 241, 242, 247 Repeated measures 171 Report writing 38–39, 88

abstract 166–168

CONSORT statement 164–166, 168, 185

introduction 168 methods 168–171 results 171–185 title 166

Reproducibility 11, 12, 130, 238, 249 Retention 97, 98–99

Risedronate 28, 191, 196, 197, 198, 215, 217, 219, 223, 224, 227

Index 291

(13)

Safety 8, 9, 19, 28, 29, 38, 78, 82, 85, 86, 100, 101, 116, 192, 196, 197, 211, 212, 225–227, 236, 242–243, 272, 273

Sampling 7, 99, 141, 259 and randomization 20–22 Scheffe’s multiple range test 174 Selective oestrogen receptor modulators

(SERMs) 29, 193–194, 213, 217, 271

SERMs see Selective oestrogen receptor modulators

Shapiro–Francia W’ test 169, 173 Shewhart (Westgard) rules 145, 147–149 Skewness 172, 173, 174

Somatokine 274, 276

Standard deviation 1, 14, 58, 84, 147, 154, 169, 190, 222, 235, 275 RMS standard deviation 60, 61 Standardization 2, 12, 84, 256, 259, 262

and pretrial quality control 47–69 Standardized coefficient of variation 239 Standardized normal deviate 15, 173, 183 Standardized precision 61, 289

Standard operating procedures (SOP) 80, 81, 87, 153

Study contract 93

Study design 2, 3, 7–23, 35, 38, 57, 58, 59, 76, 78, 97, 166, 169, 171, 185, 238 fracture endpoints 11, 12

quantitative endpoints 13–14 Study files 94, 100

Study flow-chart 19, 33

Study initiation 95–96 Subgroup analysis 163, 262

Tartrate-resistant acid phosphatase 248, 254

Telopeptides 157, 248, 249, 250, 253 Testosterone 275

Total alkaline phosphatase 254–255 Training 11, 68, 82, 91, 95, 96, 99, 103,

109, 110, 133, 137, 148, 242

Treatment effect 2, 10, 13, 14, 18, 30, 31, 48, 58, 63, 64, 67, 86, 151–152, 163, 170, 178, 181, 183–184, 197 t statistic 171, 173, 174, 184 Tukey method 174

Ultrasonometry/ultrasonometer 3, 8, 10, 11, 17, 31, 58, 141, 185, 235, 241 equipment differences 47, 50, 59, 62,