How Aus­tralia De­liv­ers Rapid Start-up and 43.5% Re­bate for Ear­ly Phase On­col­o­gy Tri­als

About Avance Clin­i­cal

Avance Clin­i­cal is an Aus­tralian owned Con­tract Re­search Or­gan­i­sa­tion that has been pro­vid­ing high-qual­i­ty clin­i­cal re­search ser­vices to the lo­cal and in­ter­na­tion­al drug de­vel­op­ment in­dus­try for 20 years. They spe­cialise in work­ing with biotech com­pa­nies to ex­e­cute Phase 1 and Phase 2 clin­i­cal tri­als to de­liv­er high-qual­i­ty out­comes fit for glob­al reg­u­la­to­ry stan­dards.

As on­col­o­gy spon­sors look in­ter­na­tion­al­ly to speed-up tri­als af­ter un­prece­dent­ed COVID-19 sus­pen­sions and de­lays, Aus­tralia, which has led the world in min­i­miz­ing the pan­dem­ic’s im­pact, stands out as an at­trac­tive des­ti­na­tion for ear­ly phase tri­als. This in com­bi­na­tion with the stream­lined reg­u­la­to­ry sys­tem and the fi­nan­cial ben­e­fits in­clud­ing a very favourable ex­change rate and the R & D cash re­bate makes Aus­tralia the per­fect lo­ca­tion for ac­cel­er­at­ing biotech clin­i­cal pro­grams.

Yvonne Lunger­hausen, CEO, Avance Clin­i­cal

“When we ad­vise spon­sors that Aus­tralia has a 43.5% re­bate on clin­i­cal tri­al costs it be­comes a straight­for­ward de­ci­sion for them to ini­ti­ate their tri­als in Aus­tralia. Aus­tralia’s clin­i­cal sites and in­fra­struc­ture are very much open for busi­ness,” said Avance Clin­i­cal CEO Yvonne Lunger­hausen.

Ap­prox­i­mate­ly 96% of our work is sup­port­ing small to medi­um-sized biotech­nol­o­gy com­pa­nies ex­e­cut­ing Phase 1 and Phase 2 tri­als. Our client base cur­rent­ly ex­tends across North Amer­i­ca, Cana­da, New Zealand, Eu­rope and Asia.

“Work­ing with the Avance Team has helped us to de­vel­op and com­plete high qual­i­ty and com­pli­ant clin­i­cal stud­ies. I es­pe­cial­ly ap­pre­ci­ate their pen­chant for com­mu­ni­ca­tion, qual­i­ty and prag­ma­tism.” – Sr. Vice Pres­i­dent, Reg­u­la­to­ry, Qual­i­ty & Clin­i­cal Af­fairs, Atossa Ge­net­ics, Inc

“We of­fer 20-years of ex­pe­ri­ence in the CRO sec­tor ser­vic­ing biotech com­pa­nies from around the globe. The de­mand for our ser­vices is dri­ven by our sci­en­tif­ic and re­search ex­cel­lence, stream­lined reg­u­la­to­ry en­vi­ron­ment, ad­vanced health­care sys­tem,” said Yvonne Lunger­shausen.

A re­view of da­ta from Tri­al­Trove re­veals that to date there are ap­prox­i­mate­ly 100 Phase 1 tri­als on­go­ing or planned to be ini­ti­at­ed in Aus­tralia by biotech’s in 2020 com­pared with over 500 Phase 1 tri­als planned to ini­ti­ate in the US. While Aus­tralia per­forms well in this space on a glob­al stage there re­mains sig­nif­i­cant op­por­tu­ni­ty for biotechs to take ad­van­tage of Aus­tralia’s world-class ear­ly phase tri­als ecosys­tem.

Learn more and reg­is­ter to watch our On­col­o­gy ca­pa­bil­i­ties pre­sen­ta­tion.

Avance Clin­i­cal is per­fect­ly placed to part­ner with biotechs for the ear­ly clin­i­cal de­vel­op­ment of their on­col­o­gy as­sets

Gabriel Krem­mid­i­o­tis, Chief Sci­en­tif­ic Of­fi­cer, Avance Clin­i­cal

More than 20% of Avance Clin­i­cal’s stud­ies are in the On­col­o­gy ther­a­peu­tic area. Af­ter con­duct­ing more than 30 stud­ies over the past 4 years and man­ag­ing a to­tal of over 5000 pa­tients this ex­pe­ri­ence has en­abled Avance Clin­i­cal to de­vel­op strong site and in­ves­ti­ga­tor re­la­tion­ships and best in class ca­pa­bil­i­ties in the con­duct of sin­gle cen­tre Phase 1 to mul­ti-cen­tre Phase 2 tri­als.

“Aus­tralia is an ide­al hub for ear­ly phase on­col­o­gy tri­als and many in­ter­na­tion­al biotech and phar­ma com­pa­nies launch ear­ly phase clin­i­cal eval­u­a­tion of their pro­grams in Aus­tralia,” says Chief Sci­en­tif­ic Of­fi­cer, Gabriel Krem­mid­i­o­tis.

Break­ing this out fur­ther Avance Clin­i­cal’s On­col­o­gy ther­a­peu­tic in­di­ca­tion ex­pe­ri­ence in­cludes:

• Breast Can­cer
• Acute Myeloid Leukemia
• Sol­id Tu­mors
• Gy­ne­co­log­ic Ma­lig­nan­cies
• Gas­tric Can­cer
• Dif­fuse In­trin­sic Pon­tine Glioma (DIPG)
• Glioblas­toma Mul­ti­forme
• B-cell Lym­phoma
• Col­orec­tal Can­cer
• BRAF mu­ta­tion-neg­a­tive Metasta­t­ic Melanoma
• Metasta­t­ic Re­nal Can­cer
• Mam­mo­graph­ic Breast Den­si­ty
• Acute Leukemia
• Up­per Limb Sec­ondary Lym­phede­ma

Lever­ag­ing deep ex­pe­ri­ence in On­col­o­gy clin­i­cal tri­als and the lat­est in­no­va­tion in study de­sign

Based on Avance’s’ ex­pe­ri­ence in these in­di­ca­tions and hav­ing man­aged many ear­ly Phase on­col­o­gy tri­als in the past 4 years Avance is able to rec­om­mend to clients a num­ber of ear­ly-phase study de­sign el­e­ments that are con­sid­ered “best re­turn on in­vest­ment” for FIH prod­ucts. Such de­signs in­cor­po­rate the fol­low­ing key el­e­ments:

• An ac­cel­er­at­ed dose-es­ca­la­tion part, in­clud­ed in the dose-es­ca­la­tion com­po­nent of a Phase I study. This de­sign ac­cel­er­ates dose es­ca­la­tion through the ini­tial sub­ther­a­peu­tic dos­es.
• In­clu­sion of a com­bi­na­tion arm to eval­u­ate the safe­ty of the in­ves­ti­ga­tion­al agent when com­bined with an ap­proved agent. Eval­u­a­tion of the com­bi­na­tion is in­clud­ed in the dose-es­ca­la­tion phase with the com­bi­na­tion off-set to the monother­a­py of the in­ves­ti­ga­tion­al agent by one dose co­hort.
• In­clu­sion of a se­quen­tial monother­a­py arm in ran­domised Phase 2 tri­als where the new in­ves­ti­ga­tion­al prod­uct is be­ing eval­u­at­ed in a com­bi­na­tion set­ting in­volv­ing the stan­dard of care (SOC) (e.g. Keytru­da plus/mi­nus the in­ves­ti­ga­tion­al agent). This de­sign al­lows the ac­qui­si­tion of da­ta on the in­ves­ti­ga­tion­al prod­uct used as monother­a­py while on­ly us­ing two treat­ment arms.

“Avance’s team and net­work of ex­pe­ri­enced clin­i­cal re­search in­ves­ti­ga­tors and sites have the breadth and depth of ex­per­tise nec­es­sary to suc­cess­ful­ly con­duct Phase I and Phase II on­col­o­gy tri­als across all tu­mour types, in tu­mour-spe­cif­ic or mol­e­c­u­lar-tar­get-spe­cif­ic set­tings,” com­ments Gabriel Krem­mid­i­o­tis, Avance Clin­i­cals Chief Sci­en­tif­ic Of­fi­cer.

Avance has em­bed­ded on­col­o­gy ex­per­tise at all lev­els and de­part­ments to en­sure the com­plex­i­ty of each on­col­o­gy tri­al is un­der­stood, and tri­al ob­jec­tives are de­liv­ered.

Un­pack­ing the Aus­tralian Ad­van­tage

The fast-reg­u­la­to­ry ap­proval en­vi­ron­ment, the avail­abil­i­ty of key opin­ion leader ex­per­tise and high-qual­i­ty clin­i­cal re­search sites in Aus­tralia pro­vides an ide­al set­ting for the fast and qual­i­ty ex­e­cu­tion of clin­i­cal tri­als.

The world’s fastest Study Start

The Aus­tralian reg­u­la­to­ry body for clin­i­cal tri­als, the Ther­a­peu­tic Goods Ad­min­is­tra­tion (‘TGA’), of­fers two schemes for con­duct­ing clin­i­cal tri­als in Aus­tralia; the CTN Scheme and the CTX Scheme. Most clin­i­cal tri­als ini­ti­at­ed in Aus­tralia are un­der the CTN Scheme. The CTN Scheme in­volves a sim­ple no­ti­fi­ca­tion process fol­low­ing Ethics Com­mit­tee (hos­pi­tal or site net­work-based re­view com­mit­tees) ap­proval for the study. It is im­por­tant to note that an ac­tive IND is not re­quired to ini­ti­ate tri­als in Aus­tralia un­der the CTN or CTX Scheme.

Key points in­clude:

• Site Ini­ti­a­tion Vis­it (SIV) and Study Start can be achieved in 5-6 weeks.
• Work­ing with­in this ro­bust and ef­fi­cient frame­work ex­pe­dites the process of run­ning a clin­i­cal tri­al.
• No IND re­quired for clin­i­cal re­search tri­als
• Full GMP ma­te­r­i­al is not man­dat­ed for Phase I clin­i­cal re­search tri­als

Re­bate of Clin­i­cal Tri­al Costs

Ad­min­is­tered by In­no­va­tion Aus­tralia and as­sist­ed by AusIn­dus­try and the Aus­tralian Tax­a­tion Of­fice (ATO), The Aus­tralian Gov­ern­ment’s Re­search and De­vel­op­ment Tax In­cen­tive has made Aus­tralia an at­trac­tive des­ti­na­tion to take ad­van­tage of R&D ini­tia­tives.

Key points in­clude:

• Ide­al for com­pa­nies with an ag­gre­gat­ed turnover of less than $20 mil­lion that are in a tax loss po­si­tion.
• Re­bate up to 43.5 cents from every dol­lar spent on R&D
• Man­age cash-flow
• Im­prove R&D project and knowl­edge man­age­ment
• En­sure com­pli­ance with R&D leg­is­la­tion

Work­ing with Eth­i­cal Re­view Process for rapid Start-up

Se­lec­tion of ap­pro­pri­ate HRECs for ear­ly phase on­col­o­gy tri­als in Aus­tralia is of pri­ma­ry im­por­tance in at­tain­ing a fast start-up and tri­al com­ple­tion. The Avance team us­es its ex­pe­ri­ence with a net­work of over 30 sites in Aus­tralia in prepar­ing HREC ap­proval plans which aim to fast study start with a min­i­mal num­ber of sub­mis­sions. The sci­en­tif­ic and eth­i­cal re­view of clin­i­cal tri­als in Aus­tralia is man­aged by the Hu­man Re­search Ethics Com­mit­tee (HREC). To en­sure a fast start-up of clin­i­cal tri­als, Avance Clin­i­cal se­lects sites that utilise rapid HREC. All study doc­u­men­ta­tion is sub­mit­ted elec­tron­i­cal­ly via ePro­to­col 2 weeks be­fore a meet­ing. From sub­mis­sion of the ap­pli­ca­tion to com­mu­ni­ca­tion of the re­view de­ci­sion, these HREC have an ap­prox­i­mate turn­around time of 20 work­ing days. Due to this stream­lined reg­u­la­to­ry and eth­i­cal re­view process, Avance Clin­i­cal can achieve a Site Ini­ti­a­tion Vis­it (SIV) and com­mence a study with­in 5 – 6 weeks of sub­mis­sion to the HREC.

“Avance’s sci­en­tif­ic and med­ical af­fairs team as­sists clients to nav­i­gate reg­u­la­to­ry sub­mis­sions and ethics study ap­proval through the pro­vi­sion of ad­vice re­lat­ing to the con­tent of In­ves­ti­ga­tors Brochures and pro­posed study de­signs and pro­to­cols. This en­sures speed of ethics re­view and ap­proval,” says Gabriel Krem­mid­i­o­tis, Avance Clin­i­cal’s Chief Sci­en­tif­ic Of­fi­cer.

Case Study: Avance Clin­i­cal – The Clin­i­cal Tri­al Check­list – How we work

Site Se­lec­tion and Ac­ti­va­tion

Avance Clin­i­cal has a sig­nif­i­cant data­base of clin­i­cal re­search sites that we ap­proach for on­col­o­gy stud­ies. Our fea­si­bil­i­ty strat­e­gy in­volves ini­tial reach out to Key Opin­ion Lead­ers (KOLs) in Aus­tralia (and if ap­plic­a­ble, oth­er coun­tries through our part­ner CROs). Our aim is to find in­flu­en­tial KOLs that ac­tive­ly per­form for stud­ies to se­lect as our key sites. The im­pact of this is that oth­er sites will be drawn to par­tic­i­pa­tion based on the in­volve­ment of the KOL.

Fol­low­ing the ini­tial reach out and ex­pres­sion of in­ter­est by the in­ves­ti­ga­tor, we send the in­ves­ti­ga­tors in­for­ma­tion and a ques­tion­naire for the study and en­gage them through ei­ther a phone call or in-per­son con­ver­sa­tion. If the in­ter­est­ed in­ves­ti­ga­tor has the tar­get­ed pa­tient pop­u­la­tion, we fol­low up with the con­duct of a pre-study site as­sess­ment vis­it to con­firm the qual­i­fi­ca­tion of the site.

Man­ag­ing Pa­tient Ac­cru­al

Our strat­e­gy for man­ag­ing pa­tient re­cruit­ment in­cludes prospec­tive, dy­nam­ic and ret­ro­spec­tive as­pects.

We prospec­tive­ly gen­er­ate ac­cru­al es­ti­mates ob­tained dur­ing ini­tial site fea­si­bil­i­ty. The process in­volves con­sul­ta­tion with prospec­tive study in­ves­ti­ga­tors on the pa­tient pop­u­la­tion to be ac­crued to the study as well as con­sid­er­a­tion of the pro­posed study el­i­gi­bil­i­ty cri­te­ria and any oth­er con­cur­rent com­pet­ing tri­als.

Fur­ther­more, our pro­jec­tions for pa­tient re­cruit­ment and our es­ti­mate of site num­ber re­quire­ments take in­to con­sid­er­a­tion time­frames and ac­cru­al rates of stud­ies we have man­aged in the past, plus bench­mark re­cruit­ment da­ta from Tri­al­Trove as well as pub­lic do­main da­ta avail­able for com­plet­ed stud­ies of sim­i­lar de­sign, pa­tient num­ber and dis­ease.

Bio­met­rics & Med­ical Writ­ing Con­sid­er­a­tions

Avance Clin­i­cal has de­vel­oped ro­bust bio­met­rics process­es for key op­er­a­tional as­pects of stud­ies in­clud­ing for the da­ta man­age­ment, bio­sta­tis­tics and med­ical writ­ing de­liv­er­ables. The Avance Clin­i­cal da­ta man­age­ment and med­ical writ­ing teams pro­vide a nim­ble and ful­ly in-house so­lu­tion. The ad­van­tage is stream­lined de­liv­ery in­clud­ing the fol­low­ing in­dica­tive time­lines:

*This time­line re­lies on time­ly re­spons­es from all stake­hold­ers re­view­ing the draft Case Re­port Form. How­ev­er, the ex­pe­ri­enced Avance Da­ta Man­age­ment team will dri­ve this process.

• The Avance Clin­i­cal bio­sta­tis­tics team is al­so a full in-house ser­vice and co-lo­cat­ed with the da­ta man­age­ment team in the Ade­laide (Aus­tralia) of­fice. This cre­ates adapt­abil­i­ty and flex­i­ble de­liv­ery due to their in­creased abil­i­ty for re­al-time com­mu­ni­ca­tion and prob­lem solv­ing.
• Fol­low­ing the pro­vi­sion of the draft Ta­bles List­ing and Fig­ures (TLFs) to our clients for re­view, the com­ple­tion of the fi­nal TLFs and the Clin­i­cal Study Re­port is re­liant on the re­view time from the client team.
• Our Sta­tis­ti­cal and Phar­ma­co­ki­net­ics Ser­vices team ser­vices con­form to the reg­u­la­to­ry-com­pli­ant CDISC mod­el, with a fo­cus on the SDTM and ADaM stan­dards and their sup­port­ing doc­u­men­ta­tion. We en­sure full da­ta trace­abil­i­ty and track val­ue lev­el meta­da­ta so that our sup­port­ing De­fine.xml com­plies with Pin­na­cle21 val­i­da­tion and our de­liv­er­ables are sub­mis­sion-ready for your clin­i­cal re­search tri­al.

The Clin­i­cal Project Team

Avance pro­vides each tri­al with a ded­i­cat­ed Clin­i­cal Project Man­ag­er (CPM) to en­sure that mile­stones are reached, time­lines are met and that our clients re­ceive ef­fec­tive com­mu­ni­ca­tion and on­go­ing sta­tus re­ports.
From the first con­ver­sa­tion to the de­liv­ery of the fi­nal re­port, our clients are ful­ly in­formed through­out the process; ir­re­spec­tive of project com­plex­i­ty.

Our CPM will be in­volved in all as­pects of clin­i­cal tri­al man­age­ment, in­clud­ing:

• Site fea­si­bil­i­ty as­sess­ments, in­ves­ti­ga­tor se­lec­tion, and site se­lec­tion
• Study de­sign and Pro­to­col re­view
• De­vel­op­ment of pa­tient in­for­ma­tion and con­sent forms
• Ethics Com­mit­tee sub­mis­sions
• Re­view of eCRF de­sign and de­vel­op­ment
• Over­sight of site mon­i­tor­ing ac­tiv­i­ties & cross-func­tion­al man­age­ment.

The Avance CPM is al­so the sin­gle point of con­tact for our clients. Fol­low­ing the award of the study to Avance, the CMP will or­gan­ise a study Kick-Off meet­ing in­volv­ing both the client team and key Avance team as­signed to the project. The CPM then li­ais­es with all Avance teams in­volved through­out the study to man­age the study time­lines, de­liv­er­ables and over­all com­mu­ni­ca­tions. The or­gan­i­sa­tion­al chart be­low is in­dica­tive of the project team set-up.

The Avance team is a high­ly ex­pe­ri­enced, stream­lined team with a ‘can-do’, so­lu­tion fo­cussed mind­set in­clud­ing a very ex­pe­ri­enced team of Project Man­agers.

Avance Clin­i­cal has the ther­a­peu­tic ex­pe­ri­ence, flex­i­ble and ro­bust qual­i­ty process­es and ex­pe­ri­enced team nec­es­sary to sup­port biotech and phar­ma com­pa­nies to ex­pe­dite the de­vel­op­ment of much need­ed new ther­a­pies and we wel­come the op­por­tu­ni­ty to dis­cuss your pro­gram fur­ther and ex­plore how we can best sup­port your de­vel­op­ment needs.

Ro­bust Sys­tems that Dri­ve Qual­i­ty

Avance un­der­stands that the suc­cess of clin­i­cal pro­gram de­liv­ery is al­so un­der­pinned by hav­ing ro­bust sys­tems that dri­ve qual­i­ty. From the abil­i­ty to de­vel­op eCRFs util­is­ing Medrio or Me­di­da­ta, the re­view and analy­sis of da­ta util­is­ing Med­DRA and WHO-DD for cod­ing, Phoenix Win­Non­lin for Phar­ma­co­ki­net­ic and Phar­ma­co­dy­nam­ic analy­sis, SAS for sta­tis­ti­cal analy­sis and CDISC ca­pa­bil­i­ties Avance has a full suite of best in class sys­tems to de­liv­er qual­i­ty out­comes. Pro­gram de­liv­ery is al­so sup­port­ed by the Flex Data­bas­es Clin­i­cal Tri­al Man­age­ment Sys­tem and eQual­i­ty Man­age­ment Sys­tem and eLearn­ing Man­age­ment Sys­tem from Mas­ter­Con­trol.