Hop­kins work­ing to shorten time needed for drug ap­provals

Re­searchers seek to use ER tri­als dur­ing se­ri­ous out­breaks of dis­eases

Baltimore Sun - - FRONT PAGE - By Mered­ith Cohn

Fed­eral ap­proval for a new drug can take a decade or more, but re­searchers at the Johns Hop­kins Univer­sity are study­ing a way to shave years off the process for med­i­ca­tions de­signed for se­ri­ous out­breaks of flu, Ebola or other in­fec­tious dis­eases.

The re­searchers want to con­duct tri­als in emer­gency rooms where large num­bers of peo­ple sick with these some­times deadly dis­eases of­ten end up. The doc­tors are poised to launch a trial run at Hop­kins dur­ing the com­ing flu sea­son — and us­ing al­ready ap­proved an­tivi­ral drugs such as Tam­i­flu — to show vol­un­teers can quickly and prop­erly be pooled in such en­vi­ron­ments.

“Nor­mally you do tri­als in doc­tors’ of­fices or in­pa­tient wards with 100 or 200 sites of­ten needed over sev­eral sea­sons be­cause each site may only en­roll one to three peo­ple,” said Dr. Richard Roth­man, a pro­fes­sor of emer­gency medicine in the Johns Hop­kins Univer­sity School of Medicine who is co-lead­ing the study. “Here in the emer­gency de­part­ment, a lot of peo­ple come in sick. That cre­ates an op­por­tu­nity.”

Roth­man and Dr. Andrea Du­gas, an as­sis­tant emer­gency medicine pro­fes­sor at Hop­kins, want to show that emer­gency de­part­ments can cut drug study time while not threat­en­ing the built-in pro­tec­tions for vol­un­teers in the U.S. Food and Drug Ad­min­is­tra­tion’s drug ap­proval process.

Drugs typ­i­cally go through sev­eral rounds of in­creas­ingly larger clin­i­cal tri­als to en­sure they are first safe and then ef­fec­tive.

The study lead­ers be­lieve emer­gency rooms could ac­cel­er­ate the process, es­pe­cially for drugs fur­ther along in the ap­proval pipe­line. That could quickly bring the most promis­ing new ther­a­pies to large num­bers of peo­ple ahead of, or even dur­ing, a pub­lic health emer­gency, Roth­man said.

In the Hop­kins study, emer­gency room staff will eval­u­ate pa­tients for flu no mat­ter their pri­mary com­plaint and test those with symp­toms, Roth­man said. They will use a screen­ing process pre­vi­ously de­vel­oped at Hop­kins that has proved ef­fec­tive in iden­ti­fy­ing flu pa­tients who could ben­e­fit from the an­tivi­rals.

The test and screen­ing re­sults will be en­tered into elec­tronic med­i­cal records, where doc­tors will be able to iden­tify good study can­di­dates. Flu pa­tients will be pro­vided all the stan­dard in­for­ma­tion about the drug’s risks and ben­e­fits. Those who could ben­e­fit from the drugs will get them whether they par­tic­i­pate in the study or not. But those who volunteer will be fol­lowed by re­searchers for two weeks and pro­vided fol­low-up care if needed.

Ev­ery­one with the flu also will be in­structed on how to care for them­selves and pre­vent spread of the virus, Roth­man said.

Most doc­tors’ of­fices and hospi­tals don’t bother to test for the flu, which typ­i­cally passes af­ter a mis­er­able week or so of cough­ing, ach­i­ness and fever.

Pub­lic health of­fi­cials track flu out­breaks by log­ging those who dis­play in­fluenza-like ill­nesses dur­ing vis­its to doc­tors and hospi­tals. The U.S. Cen­ters for Dis­ease Con­trol and Pre­ven­tion re­ports that flu sick­ens mil­lions ev­ery year across the coun­try, hos­pi­tal­izes hun­dreds of thou­sands and con­trib­utes to the deaths of thou­sands.

Roth­man doesn’t an­tic­i­pate trou­ble en­rolling enough peo­ple for the study be­cause the emer­gency room over­flows with suf­fer­ers ev­ery flu sea­son, which typ­i­cally be­gins in late fall and lasts un­til spring

If re­searchers are able to show that this is an ef­fec­tive means of en­rolling trial par­tic­i­pants, the struc­ture could be repli­cated at other hospi­tals and the time needed for drug ap­proval could be slashed by two to five years, Roth­man said.

Roth­man said emer­gency rooms haven’t been con­sid­ered as study sites in the past be­cause so-called rapid tests didn’t ex­ist five years ago for flu or other in­fec­tions, and emer­gency rooms weren’t equipped to bring pa­tients back to learn their re­sults days or a week later.

Eth­i­cal con­sid­er­a­tions were also a factor; emer­gency de­part­ments can be chaotic and scary, and peo­ple who go there feel sick enough to seek im­me­di­ate care, said Dr. Matthew Wy­nia, di­rec­tor of the Cen­ter for Bioethics and Hu­man­i­ties at the Univer­sity of Colorado, who has stud­ied tri­als con­ducted dur­ing emer­gen­cies.

These pa­tients might be less able to un­der­stand they are be­ing asked to en­ter a study, Wy­nia said. Or they might be es­pe­cially sus­cep­ti­ble to what he called the “ther­a­peu­tic mis­con­cep­tion”— that they are def­i­nitely go­ing to ben­e­fit med­i­cally, which is not al­ways the case in a study.

“The last thing you want is dis­trust in the com­mu­nity,” he said.

Get­ting com­mu­nity buy-in ahead of time would be use­ful in the event of a deadly out­break such as Ebola, in which pa­tients in the emer­gency room might be too in­ca­pac­i­tated or fright­ened to give true con­sent, Wy­nia said. Hop­kins likely would seek such com­mu­nity con­sent by con­duct­ing meet­ings with peo­ple in the ar­eas it serves.

For the proof-of-con­cept study with the flu, he said, there’s not much down­side. Vol­un­teers are likely to get bet­ter care be­cause ev­ery­one would be tested and screened for ap­proved an­tivi­rals and no one would get the drugs who shouldn’t.

He also said there is a press­ing need to speed ap­provals for new ther­a­pies, es­pe­cially those meant for out­breaks of se­ri­ous in­fec­tious dis­eases. Flu of­fers an in­valu­able op­por­tu­nity to pre­pare for fu­ture pub­lic health emer­gen­cies be­cause so many are sick­ened each year.

Wy­nia also serves on the Na­tional Acad­emy of Medicine’s Fo­rum on Med­i­cal and Pub­lic Health Pre­pared­ness for Cat­a­strophic Events, which he said has held work­shops on how to con­duct rapid re­search dur­ing pub­lic health emer­gen­cies.

“It’s ac­tu­ally un­eth­i­cal not to do these kinds of projects,” he said. “When Ebola is at our shores, it’s not the same as a flu epi­demic. The level of fear changes, the ca­pac­ity to walk peo­ple into a room and get con­sent gets harder. This [study] will show what you can do in a real epi­demic.”

Another po­ten­tial ben­e­fit of cut­ting the ap­proval time for es­sen­tial new drugs aimed at dis­as­ters is re­duc­ing their de­vel­op­ment cost, of­ten es­ti­mated at more than $1 bil­lion, Wy­nia said. That could lure more phar­ma­ceu­ti­cal com­pa­nies to de­velop ther­a­pies that might rarely be needed but are dan­ger­ous to go with­out.

The Hop­kins study is be­ing un­der­taken with $4.2 mil­lion in fed­eral fund­ing un­der a co­op­er­a­tive agree­ment with the Bio­med­i­cal Ad­vanced Re­search and De­vel­op­ment Author­ity, or BARDA, a di­vi­sion of the Of­fice of the As­sis­tant Sec­re­tary for Pre­pared­ness and Re­sponse in the U.S. De­part­ment of Health and Hu­man Ser­vices.

In a state­ment, BARDA of­fi­cials agreed that time and ex­pense could be cut sig­nif­i­cantly by more ef­fi­ciently en­rolling pa­tients in tri­als, which also could make drugs avail­able to pa­tients sooner. Such a process could be­come es­pe­cially im­por­tant in re­duc­ing the level of dis­ease and sav­ing lives dur­ing an emerg­ing pan­demic be­cause vac­cines are un­likely to be avail­able.

Other ef­forts are un­der­way to shorten the de­vel­op­ment time for drugs and vac­cines, such as us­ing the same plat­form, or tech­nol­ogy, for ther­a­pies for sim­i­lar vir­u­lent in­fec­tions, the of­fi­cials said. Re­searchers also use chal­lenge stud­ies, in which vol­un­teers are in­fected with a virus so re­searchers don’t have to wait for peo­ple to be­come sick to test a treat­ment. The Univer­sity of Mary­land used such a study for a re­cently ap­proved cholera vac­cine it de­vel­oped and is us­ing it to test a Zika vac­cine can­di­date.

Emer­gency de­part­ments may of­fer another means to cut time­lines, BARDA of­fi­cials said, and the Hop­kins study is be­gin­ning to ad­dress how to do it prop­erly.

“The ED en­vi­ron­ment presents an ideal en­vi­ron­ment in some re­spects for the stud­ies,” the of­fi­cials said. “Cost sav­ings can be tremen­dous for more ef­fi­ciently en­rolling sub­jects into clin­i­cal tri­als needed to de­velop new and more ef­fec­tive ther­a­peu­tics (and di­ag­nos­tics) for pa­tients.”


Dr. Richard Roth­man, a Hop­kins School of Medicine pro­fes­sor, is a co-leader of the study. He wants to show that emer­gency de­part­ments can cut drug ap­proval time.

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