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Data banks and clinical trials: From adversaries to complementary tools
68
Abstracts Sample Size Considerations in Chronic Disease Clinical Trials: Number of Patients Versus Follow-up Time M. B a u e r , C R e d m o n d , a n d B B a r t o n , LJmvcrs~ty ot P;ttsbure, h, lYnnsyh,ama (03) The p o w e r and the size ot tests comparing the exponential taflure rates ot two treatments d e p e n d on the n u m b e r of o b s e r v e d t a f l u r e s The tollow-up tlme needed to observe the lequlred n u m b e r of lallures can be shortened by increasing the n u m b e r ot patients entered on the study Conversely, the n u m b e r ot patients required can be minimized bv Encreasing the duration of follow-up The NSABP Statistical Unit has developed a c o m p u t e r program [follow tng George and De~,u, ] Chron D~s , 1974] which permits the user to explore mteractivelv the relationships a m o n g s a m p l e size, tolh)w-up time and p o w e r for an}' s p e c m e d ,.ah.les ot tt~e failure rates and test size Some of the ethical, practical and statistical issues revolved m balancing sample s~ze versus follow-up time will be discussed Example-, based on data ~lom NSABP Stage 1 and Stage IJ breast cancer clinical trials ',','ill be presented
Comparison of Estimated Patient Accrual and Sample Size from a Ptlot Study and Trial Data Involving Acute Disease N o r m a C. Fox, T y l e r D H a r t w e l l , W K e n n e t h Poole, a n d S u z a n n e M u l h n , Re:catch Triangle Institute, Research Triangle Park, North Carohna (04) Fhe Multlcenter Investigation lor the Limitation ot lntarct Size (MILLS) conducted ,i pilot ,-,tudv d u r i n g the p l a n n i n g p h a s e of the chnlcal trial to determine the estimated proportions and n u m b e r of acutely ill patients ot various tvpes These g r o u p i n g s were comphcated ,,ersus u n c o m p h c a t e d patients, 0-."4 hours versus ~ 18 h o u l s trom t.me ot onset to treatment, and myocardial infarction cont~rmed v e r s u s not conl~rmed These estimated proportions, and n u m b e r s and those trom other patxent g r o u p s ot the pilot study are compared to the trial's llrst two year's experience C o n s e q u e n c e s w~th regard to estimates ot pat,ent accrual anct ,-,an~ph? size tor h y p o t h e s i s testing are d~scussed
Johnson and Johnson's Live for Life Program T y l e r t t a r t w e l l , Paul Stolley, P h f l , p [ h s e r c h i a , J o a n D a v i e s , a n d J o h n R a s s w e f l e r , Research Triangle Institute, Rc,,earch "l'ru~n,~le Park, North Carohna (05) lh~s paper will describe an o n g o i n g trial to e~aluate Johnson and Johnson's [,lye tot l.tte Program This program Js a health p r o m o t i o n ettort in the w o r k s e t t m g d e s ~ g n e d to encourage employees t o t o l l o w htestyles which will result in good health The health habits and htestyle changes that are be,ng studied include reducing s m u k l n g , controlling blood pressure, lowering cholesterol le~,els by diet, tollowmg a regular exercise program, m a n a g i n g stress, reduc,ng excess weight, and increasing health knowledge To lnveMigate the elhcao., ot the Live tor Llie Program .i two-year quas~-exper~mental design is being used which in~olves tour Johnson and Johnson plants in New ]ersey which receive the Live tor l,lte Program while live other plants participate as "controls " Data analysis will involve c o m p a r i s o n s ot several d~tterent g r o u p s on the xarlables ot Mterest including treatment versus control plants tor all employees and volunteers m treatment and control plants Analysis will primarily b e t n v o l v e d w~th comparisons based on c h a n g e s t r o m basehne le~ els
Data Banks and Clinical Trials: From Adversaries to Complementary Tools S e l m a C. K u m t z , C y n t h i a ( ; r o s s , a n d A l b e r t H e y m a n , ()BFS, NINCDS, NIH. Bethesda, Maryland (06) There currently exists a misconception which attei'f?pts to place randomized contiolled chn~cal trials and data banks as o p p o s i n g Iorces with the same goals A chnlcal data bank as used in the national pilot Stroke and Traumatic Coma Data Banks ~s a collection ol patient observations from multiple hospital centers each containing patients" medical history, description ot the onset ot the d~sease, therapy and outcome recorded t h r o u g h o u t the patients chnleal course according to an established set of detlnltlons lhese data are entered, stored and retrieved In a rapid, flexible m a n n e r through the use ot a c o m p u t e r system which retains rntormatton on the temporal relationships of data The ,~tudles generated lrom the data banks are ob,,er', atlonal They can either describe disease c¢~ur,.,e or pro', ide association,.., arnc, ng premorbld character-
Abstracts
69 lstics, t r e a t m e n t l n t e r v e n h o n s a n d o u t c o m e variables Data on over 600 stroke patients collected d u n n g this pilot project p r o v i d e e x a m p l e s of the m e c h a n i s m t h r o u g h w h i c h data b a n k s can benefit future cllmcal trials T h e data b a n k s can develop d i a g n o s t i c g u i d e l i n e s for d t s e a s e classihcatlon a n d for l d e n t l f y m g patient s u b g r o u p s that m a y be a p p r o p n a t e for e n t r y into future clinical trials A s s o c i a t i o n s a m o n g ,ntervent~on a n d o u t c o m e m a y generate h y p o t h e s e s for f u r t h e r s t u d y with specified s u b g r o u p s of patients In a d d i t i o n , the data collection process a n d c o m p u t e r s y s t e m utilized p r o v i d e a m e t h o d o l o g y a n d t e c h n o l o g y w h i c h can be eftectwely u s e d in s t u d i e s with s t a n d a r d i z e d t r e a t m e n t protocols T h e s e three areas will be d i s c u s s e d with e m p h a s i s on c o m p l e m e n t a r y benefits ot clinical data b a n k s a n d clinical trials
A Clinical Data Bank Approach to Orthognathic Surgery Research C e l b P h l l h p s , Un:vers:ty ot North Carohna, Chapel Hall, North Carohna (07) C o m b i n e d o r t h o d o n t i c s a n d surgical t r e a t m e n t is the m o s t rapidly g r o w i n g t r e a t m e n t m o d a h t y in d e n t i s t r y E v a l u a t i o n s of this t r e a t m e n t , w h i c h affects p h y s i o l o g i c a l a d a p t a t i o n s a n d morphological c h a n g e s , h a v e b e e n v e r y limited primarily b e c a u s e of the lack of a c o m p u t e r i z e d clinical data b a n k T h e Dentofaclal Team at the U n i v e r s i t y ot North Carolina is currently field testing a m i n i c o m p u t e r - b a s e d clinical data collection a n d storage s y s t e m w h i c h incorporates a d i v e r s e s p e c t r u m of physiological, morphological, d e m o g r a p h i c , and clinical t r e a t m e n t data T h i s s y s t e m allows for u n i f o r m data to be collected prospectively on large n u m b e r s of o r t h o g n a t h l c s u r g e r y p a t i e n t s [n t h e near future, the field testing will be e x t e n d e d to n i n e additional dental i n s t i t u t i o n s T h e p r i m a r y objective of this prolect is to develop a research oriented record s y s t e m w h i c h is an aid in g e n e r a t i n g h y p o t h e s e s on,form/function interactions It is expected that this s y s t e m will also m e e t the clinical n e e d s of the investigators for patient m a n a g e m e n t S u p p o r t e d by NIDR g r a n t # D E 05215
Insufficiency of Comparing Consecutive Trials to Prove Treatment Efficiency: An Example in Acute Lymphoblastic Leukemia (A.L.L.) Cl. C h a s t a n g ,
M.F. A u c l e r c , J P C h a n t a l o u ,
M
W e l l , CI J a c q u f l l a t , a n d F G r e m y ,
INSERM U 194, 91, Bd de l'H6pztal 75013 Parzs, France (08) Children with ALL (1288) h a v e b e e n included in c o n s e c u t i v e protocols at the t lospltal S a l t Louis (Parlsl from 1964 to 1979 (551 children before 1974, 405 in the protocol 08 LAL 74 a n d 332 m the 10 LAL 76) T h e a i m of the 08 LAL 74 w a s to evaluate the m t e r e s t of c y c l o p h o s p h a m l d e T h e d o s a g e was a d a p t e d to the severity ot the d i s e a s e d e h n e d by a three-class score, b u t the d e s i g n d i d not allow u s to p r o v e t h e interest of this a d a p t a t i o n T h e r e t o r e , we m a d e c o m p a r i s o n s b e t w e e n t h e protocols 1964-1974 ancl 08 LAL 74 w l t h m classes ot equal severity T h e histor, cal c o m p a r i s o n s (0 10 vs 0 32 five year disease-free rates~ did not c o n v m c e other researchers Moreover the c o m p a r i s o n of identical t r e a t m e n t g r o u p s in 08 LAL 74 and 10 LAL 76, initially h o m o g e n e o u s in b a s e l i n e variables, s h o w s s i g m t l c a n t differences in several aspects T h e s e a n a l y s e s s u g g e s t great caution w h e n u s i n g data b a n k s for t h e r a p e u t i c decision
Radiation Therapy Quality Control: Methodology and Results W. G r u n d y , Rad:at~on Therapy Oncology Group, Phdadelphta, Pennsylvama (O9)
Graham
A radiation t h e r a p y q u a h t y control p r o g r a m has been active at RTOG H e a d q u a r t e r s tor m o r e t h a n two y e a r s T h e C e n t e r receives t r e a t m e n t p l a n s a n d locahzatlon trims early in the t r e a t m e n t c o u r s e for r e v i e w R e c o m m e n d e d c h a n g e s to m o d i f y t r e a t m e n t to comply with the protocol can be a c c o m p h s h e d T h e p r o g r a m is p r e s e n t l y m 6 n l t o r m g 2,500 cases per a n n u m C o m p l i a n c e h a s i m p r o v e d from 81% in 1977 to 96% ,n 1980 M e t h o d o l o g y , results, a n d cost effectiveness of quality control will be d i s c u s s e d
How Valid Are the Data Collected i n a Complex Multicenter C l i n i c a l T r i a l ? M M u l h n , The Natwnal Heart, Lung, and Blood Inst:tute, Bethesda, Maryland (10) Suzanne
M a n y clinical trials h a v e b e e n c o n d u c t e d over the past few d e c a d e s a n d the validity ot the data collected a n d reported ~s a central i s s u e w h i c h u n d e r g o e s close s c r u t m y by critics This p a p e r a d d r e s s e s t e c h n i q u e s u s e d by t h e Nat,onal }leart, Lung, a n d Blood Institute (NHLBI) Program
Abstracts Sample Size Considerations in Chronic Disease Clinical Trials: Number of Patients Versus Follow-up Time M. B a u e r , C R e d m o n d , a n d B B a r t o n , LJmvcrs~ty ot P;ttsbure, h, lYnnsyh,ama (03) The p o w e r and the size ot tests comparing the exponential taflure rates ot two treatments d e p e n d on the n u m b e r of o b s e r v e d t a f l u r e s The tollow-up tlme needed to observe the lequlred n u m b e r of lallures can be shortened by increasing the n u m b e r ot patients entered on the study Conversely, the n u m b e r ot patients required can be minimized bv Encreasing the duration of follow-up The NSABP Statistical Unit has developed a c o m p u t e r program [follow tng George and De~,u, ] Chron D~s , 1974] which permits the user to explore mteractivelv the relationships a m o n g s a m p l e size, tolh)w-up time and p o w e r for an}' s p e c m e d ,.ah.les ot tt~e failure rates and test size Some of the ethical, practical and statistical issues revolved m balancing sample s~ze versus follow-up time will be discussed Example-, based on data ~lom NSABP Stage 1 and Stage IJ breast cancer clinical trials ',','ill be presented
Comparison of Estimated Patient Accrual and Sample Size from a Ptlot Study and Trial Data Involving Acute Disease N o r m a C. Fox, T y l e r D H a r t w e l l , W K e n n e t h Poole, a n d S u z a n n e M u l h n , Re:catch Triangle Institute, Research Triangle Park, North Carohna (04) Fhe Multlcenter Investigation lor the Limitation ot lntarct Size (MILLS) conducted ,i pilot ,-,tudv d u r i n g the p l a n n i n g p h a s e of the chnlcal trial to determine the estimated proportions and n u m b e r of acutely ill patients ot various tvpes These g r o u p i n g s were comphcated ,,ersus u n c o m p h c a t e d patients, 0-."4 hours versus ~ 18 h o u l s trom t.me ot onset to treatment, and myocardial infarction cont~rmed v e r s u s not conl~rmed These estimated proportions, and n u m b e r s and those trom other patxent g r o u p s ot the pilot study are compared to the trial's llrst two year's experience C o n s e q u e n c e s w~th regard to estimates ot pat,ent accrual anct ,-,an~ph? size tor h y p o t h e s i s testing are d~scussed
Johnson and Johnson's Live for Life Program T y l e r t t a r t w e l l , Paul Stolley, P h f l , p [ h s e r c h i a , J o a n D a v i e s , a n d J o h n R a s s w e f l e r , Research Triangle Institute, Rc,,earch "l'ru~n,~le Park, North Carohna (05) lh~s paper will describe an o n g o i n g trial to e~aluate Johnson and Johnson's [,lye tot l.tte Program This program Js a health p r o m o t i o n ettort in the w o r k s e t t m g d e s ~ g n e d to encourage employees t o t o l l o w htestyles which will result in good health The health habits and htestyle changes that are be,ng studied include reducing s m u k l n g , controlling blood pressure, lowering cholesterol le~,els by diet, tollowmg a regular exercise program, m a n a g i n g stress, reduc,ng excess weight, and increasing health knowledge To lnveMigate the elhcao., ot the Live tor Llie Program .i two-year quas~-exper~mental design is being used which in~olves tour Johnson and Johnson plants in New ]ersey which receive the Live tor l,lte Program while live other plants participate as "controls " Data analysis will involve c o m p a r i s o n s ot several d~tterent g r o u p s on the xarlables ot Mterest including treatment versus control plants tor all employees and volunteers m treatment and control plants Analysis will primarily b e t n v o l v e d w~th comparisons based on c h a n g e s t r o m basehne le~ els
Data Banks and Clinical Trials: From Adversaries to Complementary Tools S e l m a C. K u m t z , C y n t h i a ( ; r o s s , a n d A l b e r t H e y m a n , ()BFS, NINCDS, NIH. Bethesda, Maryland (06) There currently exists a misconception which attei'f?pts to place randomized contiolled chn~cal trials and data banks as o p p o s i n g Iorces with the same goals A chnlcal data bank as used in the national pilot Stroke and Traumatic Coma Data Banks ~s a collection ol patient observations from multiple hospital centers each containing patients" medical history, description ot the onset ot the d~sease, therapy and outcome recorded t h r o u g h o u t the patients chnleal course according to an established set of detlnltlons lhese data are entered, stored and retrieved In a rapid, flexible m a n n e r through the use ot a c o m p u t e r system which retains rntormatton on the temporal relationships of data The ,~tudles generated lrom the data banks are ob,,er', atlonal They can either describe disease c¢~ur,.,e or pro', ide association,.., arnc, ng premorbld character-
Abstracts
69 lstics, t r e a t m e n t l n t e r v e n h o n s a n d o u t c o m e variables Data on over 600 stroke patients collected d u n n g this pilot project p r o v i d e e x a m p l e s of the m e c h a n i s m t h r o u g h w h i c h data b a n k s can benefit future cllmcal trials T h e data b a n k s can develop d i a g n o s t i c g u i d e l i n e s for d t s e a s e classihcatlon a n d for l d e n t l f y m g patient s u b g r o u p s that m a y be a p p r o p n a t e for e n t r y into future clinical trials A s s o c i a t i o n s a m o n g ,ntervent~on a n d o u t c o m e m a y generate h y p o t h e s e s for f u r t h e r s t u d y with specified s u b g r o u p s of patients In a d d i t i o n , the data collection process a n d c o m p u t e r s y s t e m utilized p r o v i d e a m e t h o d o l o g y a n d t e c h n o l o g y w h i c h can be eftectwely u s e d in s t u d i e s with s t a n d a r d i z e d t r e a t m e n t protocols T h e s e three areas will be d i s c u s s e d with e m p h a s i s on c o m p l e m e n t a r y benefits ot clinical data b a n k s a n d clinical trials
A Clinical Data Bank Approach to Orthognathic Surgery Research C e l b P h l l h p s , Un:vers:ty ot North Carohna, Chapel Hall, North Carohna (07) C o m b i n e d o r t h o d o n t i c s a n d surgical t r e a t m e n t is the m o s t rapidly g r o w i n g t r e a t m e n t m o d a h t y in d e n t i s t r y E v a l u a t i o n s of this t r e a t m e n t , w h i c h affects p h y s i o l o g i c a l a d a p t a t i o n s a n d morphological c h a n g e s , h a v e b e e n v e r y limited primarily b e c a u s e of the lack of a c o m p u t e r i z e d clinical data b a n k T h e Dentofaclal Team at the U n i v e r s i t y ot North Carolina is currently field testing a m i n i c o m p u t e r - b a s e d clinical data collection a n d storage s y s t e m w h i c h incorporates a d i v e r s e s p e c t r u m of physiological, morphological, d e m o g r a p h i c , and clinical t r e a t m e n t data T h i s s y s t e m allows for u n i f o r m data to be collected prospectively on large n u m b e r s of o r t h o g n a t h l c s u r g e r y p a t i e n t s [n t h e near future, the field testing will be e x t e n d e d to n i n e additional dental i n s t i t u t i o n s T h e p r i m a r y objective of this prolect is to develop a research oriented record s y s t e m w h i c h is an aid in g e n e r a t i n g h y p o t h e s e s on,form/function interactions It is expected that this s y s t e m will also m e e t the clinical n e e d s of the investigators for patient m a n a g e m e n t S u p p o r t e d by NIDR g r a n t # D E 05215
Insufficiency of Comparing Consecutive Trials to Prove Treatment Efficiency: An Example in Acute Lymphoblastic Leukemia (A.L.L.) Cl. C h a s t a n g ,
M.F. A u c l e r c , J P C h a n t a l o u ,
M
W e l l , CI J a c q u f l l a t , a n d F G r e m y ,
INSERM U 194, 91, Bd de l'H6pztal 75013 Parzs, France (08) Children with ALL (1288) h a v e b e e n included in c o n s e c u t i v e protocols at the t lospltal S a l t Louis (Parlsl from 1964 to 1979 (551 children before 1974, 405 in the protocol 08 LAL 74 a n d 332 m the 10 LAL 76) T h e a i m of the 08 LAL 74 w a s to evaluate the m t e r e s t of c y c l o p h o s p h a m l d e T h e d o s a g e was a d a p t e d to the severity ot the d i s e a s e d e h n e d by a three-class score, b u t the d e s i g n d i d not allow u s to p r o v e t h e interest of this a d a p t a t i o n T h e r e t o r e , we m a d e c o m p a r i s o n s b e t w e e n t h e protocols 1964-1974 ancl 08 LAL 74 w l t h m classes ot equal severity T h e histor, cal c o m p a r i s o n s (0 10 vs 0 32 five year disease-free rates~ did not c o n v m c e other researchers Moreover the c o m p a r i s o n of identical t r e a t m e n t g r o u p s in 08 LAL 74 and 10 LAL 76, initially h o m o g e n e o u s in b a s e l i n e variables, s h o w s s i g m t l c a n t differences in several aspects T h e s e a n a l y s e s s u g g e s t great caution w h e n u s i n g data b a n k s for t h e r a p e u t i c decision
Radiation Therapy Quality Control: Methodology and Results W. G r u n d y , Rad:at~on Therapy Oncology Group, Phdadelphta, Pennsylvama (O9)
Graham
A radiation t h e r a p y q u a h t y control p r o g r a m has been active at RTOG H e a d q u a r t e r s tor m o r e t h a n two y e a r s T h e C e n t e r receives t r e a t m e n t p l a n s a n d locahzatlon trims early in the t r e a t m e n t c o u r s e for r e v i e w R e c o m m e n d e d c h a n g e s to m o d i f y t r e a t m e n t to comply with the protocol can be a c c o m p h s h e d T h e p r o g r a m is p r e s e n t l y m 6 n l t o r m g 2,500 cases per a n n u m C o m p l i a n c e h a s i m p r o v e d from 81% in 1977 to 96% ,n 1980 M e t h o d o l o g y , results, a n d cost effectiveness of quality control will be d i s c u s s e d
How Valid Are the Data Collected i n a Complex Multicenter C l i n i c a l T r i a l ? M M u l h n , The Natwnal Heart, Lung, and Blood Inst:tute, Bethesda, Maryland (10) Suzanne
M a n y clinical trials h a v e b e e n c o n d u c t e d over the past few d e c a d e s a n d the validity ot the data collected a n d reported ~s a central i s s u e w h i c h u n d e r g o e s close s c r u t m y by critics This p a p e r a d d r e s s e s t e c h n i q u e s u s e d by t h e Nat,onal }leart, Lung, a n d Blood Institute (NHLBI) Program