The pros and cons of a rare diseases registry

Data is a sav­iour in many set­tings, prized like gold or oil.  For rare dis­eases, its val­ue is immense, with a pow­er to accel­er­ate under­stand­ing and advance treat­ment.

Rare dis­eases – con­di­tions that affect few­er than one in 2,000 peo­ple — are at an inher­ent dis­ad­van­tage when it comes to drug devel­op­ment. Their small pop­u­la­tion sizes cre­ate logis­ti­cal, legal and eco­nom­ic road­blocks to clin­i­cal tri­als.  

Reg­istries col­late patient his­to­ries and respons­es across aspects of a par­tic­u­lar dis­ease. They can play a vital role in under­stand­ing dis­ease tra­jec­to­ry, help­ing to cre­ate clin­i­cal tri­als that meet safe­ty and effi­ca­cy cri­te­ria despite their low enrol­ment: many have few­er than 100 patients world­wide.

But as with all health­care data sets, there are con­cerns around how that data is curat­ed and used, with cam­paign­ers call­ing for greater trans­paren­cy.

Raising standards 

EURORDIS, an alliance of patient organ­i­sa­tions rep­re­sent­ing 974 rare dis­ease patient organ­i­sa­tions in 74 coun­tries, believes reg­istries are a vital com­po­nent in improv­ing the lives of the 30 mil­lion peo­ple affect­ed by rare dis­eases through­out Europe.

“They are a core part in advanc­ing knowl­edge, care and the devel­op­ment of treat­ments,” says Anna Kole, EURORDIS’s pub­lic health pol­i­cy direc­tor. “Because these con­di­tions are so rare, data is scarce and it is a strug­gle to reach the thresh­olds for clin­i­cal tri­als, care stan­dards and health pol­i­cy deci­sions.”

Pool­ing data for clin­i­cal and epi­demi­o­log­i­cal research and strat­i­fy­ing patients improves the design of clin­i­cal tri­als, she explains, and the chances of find­ing eli­gi­ble patients. It also means researchers can fol­low a cohort of patients over time to track the nat­ur­al his­to­ry of a dis­ease, help­ful both for clin­i­cal tri­als and devel­op­ing stan­dards of care, she explains. 

“It may not lead to a cura­tive treat­ment, but it can track what is work­ing and what doesn’t work to inform care for peo­ple.”

A recent EURORDIS Rare Barom­e­ter sur­vey among rare dis­ease patients record­ed 100% approval of data shar­ing for research, with 80% want­i­ng to keep a lev­el of con­trol. 

“But con­trol sim­ply means peo­ple who share their data just want to know 

the who, how and why their data might be shared – being informed, engaged and involved in where the data is help­ing research,” says Kole.

A lot of patient organ­i­sa­tions are start­ing reg­istries them­selves, she adds, because they can be piv­otal to advance prospects for their par­tic­u­lar con­di­tion. Research shows that con­di­tions with a reg­istry com­bined with a well-con­nect­ed com­mu­ni­ty of clin­i­cal spe­cial­ists and a thresh­old of pub­li­ca­tions have more poten­tial to improve care, cre­ate clin­i­cal tri­als and the oppor­tu­ni­ty to ulti­mate­ly devel­op treat­ments.

“They are seen as a way of get­ting past a bot­tle­neck,” she adds. 

Data is pro­tect­ed by a range of rel­a­tive­ly new leg­is­la­tion includ­ing Gen­er­al Data Pro­tec­tion Reg­u­la­tion (GDPR), but these were not designed with patient reg­istries in mind.

“Good and clear reg­u­la­to­ry con­trols are also key to patient reg­is­tra­tion and the GDPR can be dif­fi­cult to nav­i­gate,” says Kole. “There shouldn’t be unnec­es­sary hur­dles and in this fast-chang­ing area we need wider dis­cus­sion so that patient data can be col­lect­ed and shared more effi­cient­ly but with­out risk­ing the pri­va­cy or expec­ta­tions of patients.”

Safety fears

The ben­e­fits are clear. Patient reg­istry data suc­cess­ful­ly act­ed as the con­trol arm in a clin­i­cal tri­al for a new enzyme replace­ment treat­ment for Pompe’s dis­ease, accord­ing to a paper in the Orphanet Jour­nal of Rare Dis­eases. Pompe’s dis­ease is a glyco­gen stor­age con­di­tion that’s cur­rent­ly diag­nosed in less than 200 patients in the UK. With­out the help of the reg­istry, the drug wouldn’t have made it to a clin­i­cal tri­al and sub­se­quent approval.

But the use of patient data has a shaky her­itage. Land­mark cas­es have stoked fears over com­mer­cial access to data sets that still rever­ber­ate today, taint­ing data safe­ty assur­ances. Such cas­es include the Roy­al Free Hospital’s move to share kid­ney patient infor­ma­tion with Goodle’s Deep­Mind sub­sidiary with­out con­sent, or the NHS’s aban­doned care.data scheme. 

Like­wise, a research study into the genet­ic and envi­ron­men­tal fac­tors of autism ran into trou­ble ear­li­er this year when pro­tes­tors claimed the DNA data could be mis­used by researchers want­i­ng to cure or erad­i­cate autism rather than advance under­stand­ing.

Med­Con­fi­den­tial, an inde­pen­dent organ­i­sa­tion that cam­paigns for con­fi­den­tial­i­ty and con­sent in health and social care, believes more work is need­ed to ensure patient data is stored safe­ly and used eth­i­cal­ly.

“Every patient should know where their data is being used and there should be no sur­pris­es,” says Sam Smith, Med­Con­fi­den­tial co-ordi­na­tor. 

Smith advo­cates tighter con­sent pro­to­cols, greater trans­paren­cy and the abil­i­ty for peo­ple to check a cen­tral data­base to see where their data is being used.

“The NHS can act as hon­est bro­ker here,” he adds. “We want to see a sys­tem where a legit­i­mate researcher can log into a com­put­er to analyse the data and take the analy­sis away, not the data. This gives researchers more data and there is more account­abil­i­ty and con­fi­dence.”

Life-changing results

EURORDIS is cam­paign­ing for bet­ter patient reg­istry stan­dards and prac­tices, includ­ing shared qual­i­ty assur­ance and data secu­ri­ty stan­dards.

“In recent years, reg­istries have been cross-link­ing clin­i­cal data, con­firm­ing genet­ic muta­tions and under­ly­ing symp­toms, that helps speed this along,” adds Kole.

The cys­tic fibro­sis com­mu­ni­ty has also ben­e­fit­ed, she says, with the reg­istry used to improve stan­dards of care. Life expectan­cy for those with the con­di­tion was improved because peo­ple received care in accred­it­ed, well-net­worked cen­tres, where it was pos­si­ble to mon­i­tor and share infor­ma­tion on dosages or avoid­ing infec­tions. 

“As a result, bet­ter stan­dards of care and dis­ease man­age­ment led to a dra­mat­ic increase in life expectan­cy, thanks to the patient reg­istry.”