As researchers race to develop a COVID-19 vaccine, two Rutgers Global Health Institute core faculty members discuss how clinical trials work, the ethics of developing and distributing a vaccine, safety and efficacy in clinical trials, and what a successful vaccine may mean. Associate Professor Shobha Swaminathan is principal investigator at the Rutgers New Jersey Medical School Clinical Research Center and the medical director of Infectious Diseases Practice at University Hospital, and Michael K. Gusmano is a bioethicist and professor of health policy at the Rutgers School of Public Health.
Why is Rutgers involved in a vaccine clinical trial?
Swaminathan: It’s very important to include people from populations like our local community, which has been impacted by the COVID-19 pandemic, and suffered a higher incidence and more severe disease outcomes and needs access to vaccines that could protect them. The Rutgers New Jersey Medical School Clinical Research Center is one of over 90 clinical trial sites across the United States selected to participate in the Phase 3 Moderna COVID-19 vaccine trial. Our site has been funded by the National Institutes of Health and industry partners to conduct clinical trials for about 15 years – proudly serving local communities in the state of New Jersey while providing cutting edge research and engagement opportunities.
What are the general developmental processes in getting a COVID-19 vaccine ready for safe use? What do the different phases mean?
Swaminathan: A vaccine helps your immune system produce antibodies that can help fight and prevent infections. When researchers pursue a path to creating a new therapy, such as a vaccine, there are typically four phases to this voluntary research process.
The Moderna vaccine trial completed phase 1 of its study in July 2020 and has 600 participants enrolled in phase 2. Both remain under long-term safety follow up.
Phase 3 marks the start of large-scale testing of participants of various ages and ethnic groups across the U.S. It is the final step needed to seek the Food and Drug Administration’s approval to market the vaccine if it is found to be safe and effective.
In the phase 3 trial, some participants receive the active vaccine and others an inactive injection, and their experiences are compared. The fourth and final stage of research evaluates the long-term effects of the vaccine and its impact on other special populations such as children. The results of the Moderna phase 1 research can be reviewed here. The results of the Phase 2 research will be released soon.
Do people have to participate in these clinical studies?
Swaminathan: Participation is voluntary and requires those involved to provide informed consent – after receiving a detailed overview of the study, including possible benefits and side effects – if they want to participate. Participants also have the option to leave the study at any point. Participation in clinical trials are the only way we can find answers that will ultimately help us all overcome the COVID-19 pandemic.
How ethical is it to test people with a COVID-19 vaccine?
Gusmano: There is little question that this can be ethical, but as with all other clinical trials, it depends on the circumstances and design. If there is sufficient evidence from the bench science and animal models, it is reasonable to move to human clinical trials.
Once this happens, a vital issue is an informed consent. Questions we must ask are; Are the risks and benefits explained clearly? Have those running the trial thought carefully about the potential effects of framing on how people respond to the benefits and risks? Do they clearly understand that they may withdraw from the trial?
It is essential for all of the usual protections that Institutional Review Boards require, like carefully monitoring participants’ health with provisions in place to suspend or stop trials if there are serious adverse consequences. Within these parameters, clinical trials can be conducted in a way that would be broadly accepted as ethical.
How do researchers guarantee people’s safety during clinical trials?
Swaminathan: All participants in clinical trial are closely monitored and provided with any new safety information discovered about the vaccine
The clinical trials are coordinated and monitored by an oversight Data Safety and Monitoring Board and frequently by a Protocol Safety Review Team, which is composed of the study sponsor, NIH, and other federal officials. They review adverse events in real time to ensure that volunteer safety is prioritized. Both groups can recommend stopping or pausing the trial if needed. Local Institutional Review Boards also help protect the rights and welfare of study volunteers recruited to participate in the trials.
How do you know if a vaccine clinical trial is for you and what should people know or do before volunteering to participate?
Swaminathan: In order to be eligible for the Moderna phase 3 trial, healthy volunteers must be 18 years of age or older with no known history of the COVID-19 infection and no previous participation in an investigational coronavirus vaccine. Within this population, we are prioritizing candidates whose locations or circumstances put them at higher risk of exposure to the virus, including:
- Age 65 or older
- Essential workers in close contact with potentially infected persons, including but not limited to healthcare and hospital workers, first responders, transit employees, institutional residents or workers, factory employees, teachers, and students
- Racial and ethnic minorities at high risk for COVID-19
The study has multiple other criteria that will be reviewed with participants on an individual basis to ensure that involvement is right for them.
What are the risks associated with participating in a COVID-19 vaccine clinical trial?
Swaminathan: Enrollment in phase 3 vaccine studies is only possible because of the information from phase 1 and 2 studies. As of September 18, 2020, over 25,000 participants have been enrolled across the U.S. in the Moderna phase 3 study.
Will people be compensated for participating in a vaccine clinical trial?
Swaminathan: We respect the study participants’ time and effort in volunteering to participate in the study and they will receive some reimbursement, the details of which will be reviewed during the informed consent process.
Who will be prioritized first for the COVID-19 vaccine when it’s finally approved and how will it be made available and distributed to the public?
Gusmano: There seems to be a broad consensus that health care providers, people in high-risk categories like nursing home residents, and other essential workers should receive priority. But the federal government has not articulated clear standards and neither have most of the states. We also do not know enough about the number of doses that will be distributed to each state if and when a vaccine is approved. And we have not done sufficient planning around how the vaccines will be transported, stored, or delivered. The Centers for Disease Control and Prevention’s guidelines are vague on all of these points, and there needs to be a lot more work on this before we know how it is likely to work.
Wakati watafiti wanashindana kutengeneza chanjo ya COVID-19, wanachama wawili wa kitivo cha msingi wa Taasisi ya Afya ya Ulimwenguni ya Rutgers wanajadili jinsi majaribio ya kliniki yanavyofanya kazi, maadili ya kuendeleza na kusambaza chanjo, usalama na ufanisi katika majaribio ya kliniki, na chanjo iliyofanikiwa inaweza kumaanisha nini. Shobha Swaminathan, Mtaalamu wa Utafiti wa Matibabu wa Chuo Kikuu cha Rutgers, ni Mtaalamu wa Utafiti wa Matibabu wa Chuo Kikuu cha New Jersey, na Michael K. Gusmano, Mtaalamu wa Bioethics na Profesa wa Sera ya Afya katika Chuo Kikuu cha Rutgers. Kwa nini Rutgers inahusika katika majaribio ya kliniki ya chanjo? """Ni muhimu sana kujumuisha watu kutoka kwa idadi ya watu kama jamii yetu ya ndani, ambayo imeathiriwa na janga la COVID-19 na ilipatwa na matukio ya juu na matokeo mabaya zaidi ya ugonjwa na inahitaji upatikanaji wa chanjo ambazo zinaweza kuwalinda." Kituo cha Utafiti wa Kliniki cha Rutgers New Jersey ni moja ya zaidi ya maeneo 90 ya majaribio ya kliniki kote Marekani yaliyochaguliwa kushiriki katika jaribio la awamu ya tatu la chanjo ya Moderna COVID-19. Tovuti yetu imefadhiliwa na Taasisi za Kitaifa za Afya na washirika wa tasnia kufanya majaribio ya kliniki kwa miaka 15 - kwa fahari kuwahudumia jamii za mitaa katika jimbo la New Jersey wakati wa kutoa fursa za utafiti wa juu na ushiriki. Ni nini mchakato wa maendeleo ya jumla katika kupata chanjo ya COVID-19 tayari kwa matumizi salama? Hatua hizo tofauti humaanisha nini? "Swaminathan: ""Tumevaccinated na mfumo wa kinga ya mwili wetu na kuwezesha mfumo wetu wa kinga kutengeneza antibodies ambazo zinaweza kusaidia kupambana na kuzuia maambukizi." Watafiti wanapokuwa na mpango wa kutengeneza dawa mpya, kama vile chanjo, kwa kawaida kuna hatua nne katika mchakato huu wa utafiti wa hiari. Majaribio ya chanjo ya Moderna yalimaliza awamu ya kwanza ya utafiti wake mnamo Julai 2020 na ina washiriki 600 waliojisajili katika awamu ya pili. Wote wawili wanabaki chini ya ufuatiliaji wa usalama wa muda mrefu. Hatua ya tatu ni mwanzo wa majaribio makubwa ya washiriki wa umri mbalimbali na makundi ya kikabila kote Marekani. Hatua ya mwisho ni kutafuta idhini ya Idara ya Chakula na Dawa ya Marekani (FDA) ya kuuza chanjo hiyo ikiwa imepatikana kuwa salama na yenye ufanisi. Katika jaribio la awamu ya tatu, baadhi ya washiriki hupokea chanjo ya kazi na wengine sindano isiyofanya kazi, na uzoefu wao unalinganishwa. Hatua ya nne na ya mwisho ya utafiti ni kutathmini athari za muda mrefu za chanjo na athari zake kwa idadi nyingine maalum ya watu kama vile watoto. Matokeo ya utafiti wa Moderna ya awamu ya kwanza yanaweza kuchunguzwa hapa. Matokeo ya utafiti wa awamu ya pili yatatolewa hivi karibuni. Je, ni lazima watu washiriki katika majaribio hayo ya kliniki? Ushiriki ni wa hiari na inahitaji wale wanaohusika kutoa idhini ya ufahamu baada ya kupokea muhtasari wa kina wa utafiti, ikiwa ni pamoja na faida na athari zinazowezekana ikiwa wanataka kushiriki. Washiriki pia wana chaguo la kuondoka katika utafiti wakati wowote. Ushiriki katika majaribio ya kliniki ni njia pekee ambayo tunaweza kupata majibu ambayo hatimaye yatatusaidia sote kushinda janga la COVID-19. Ni nini kinachohitajika ili kugundua ikiwa mtu ana chanjo ya COVID-19? "Gusman: ""Hakuna shaka kwamba hii inaweza kuwa ya maadili, lakini kama ilivyo na majaribio mengine yote ya kliniki, inategemea hali na muundo." Ikiwa kuna ushahidi wa kutosha kutoka kwa sayansi ya benchi na mifano ya wanyama, ni busara kuhamia majaribio ya kliniki ya binadamu. Mara tu jambo hilo litakapotokea, jambo muhimu ni kukubali kwa habari. Maswali tunayopaswa kuuliza ni: Je, hatari na faida zimeelezwa waziwazi? Je, wale wanaofanya majaribio hayo wamefikiria kwa uangalifu kuhusu athari zinazoweza kutokea kwa watu wanaojibu kwa faida na hatari za majaribio hayo? Je, wanaelewa waziwazi kwamba wanaweza kujiondoa katika kesi hiyo? "Hii ni muhimu kwa ulinzi wote wa kawaida ambao Bodi za Mapitio ya Taasisi zinahitaji, kama vile kufuatilia kwa uangalifu afya ya washiriki na masharti ya kusimamisha au kusimamisha majaribio ikiwa kuna matokeo mabaya makubwa. """ Ndani ya vigezo hivi, majaribio ya kliniki yanaweza kufanywa kwa njia ambayo ingekubaliwa kwa ujumla kama maadili. Watafiti wanahakikishaje usalama wa watu wakati wa majaribio ya kliniki? "Wanachama wote wa majaribio ya kliniki hufuatwa kwa karibu na kupewa habari yoyote mpya ya usalama iliyogunduliwa kuhusu chanjo, ""alisema Swaminathan.""" Wao kuchunguza matukio mabaya katika muda halisi ili kuhakikisha kwamba usalama wa kujitolea ni kipaumbele. Vikundi vyote viwili vinaweza kupendekeza kukomesha au kusimamisha jaribio hilo ikiwa ni lazima. Bodi za Uhakiki za Taasisi za Mitaa pia husaidia kulinda haki na ustawi wa wajitoleaji wa utafiti waliochaguliwa kushiriki katika majaribio. Jinsi ya kujua ikiwa jaribio la chanjo ni kwa ajili yako na nini watu wanapaswa kujua au kufanya kabla ya kujitolea kushiriki? Kwa hivyo, ili kuwa na haki ya majaribio ya Moderna ya awamu ya 3, wajitoleaji wenye afya lazima wawe na umri wa miaka 18 au zaidi na wasiwe na historia inayojulikana ya maambukizi ya COVID-19 na wasiwe na ushiriki wa awali katika chanjo ya uchunguzi ya coronavirus. "Wanafunzi wanaohusika katika utafiti huo ni wale ambao ""wana hatari kubwa ya kuambukizwa virusi vya corona"" na ""wana umri wa miaka 65 au zaidi"" na ""wafanya kazi muhimu katika mawasiliano ya karibu na watu wanaoweza kuambukizwa, ikiwa ni pamoja na lakini si tu kwa wafanyakazi wa huduma za afya na hospitali, wa kwanza kujibu, wafanyakazi wa usafiri, wakazi wa taasisi au wafanyakazi, wafanyakazi wa kiwanda, walimu na wanafunzi." Kuna hatari gani zinazohusiana na kushiriki katika majaribio ya kliniki ya chanjo ya COVID-19? "Swaminathan alisema: ""Uandikishaji katika masomo ya chanjo ya awamu ya tatu inawezekana tu kwa sababu ya habari kutoka kwa masomo ya awamu ya kwanza na ya pili.""" Kufikia Septemba 18, 2020, zaidi ya washiriki 25,000 wamejiandikisha kote Marekani katika utafiti wa Moderna wa awamu ya 3. Je, watu watalipwa kwa kushiriki katika majaribio ya kliniki ya chanjo? "Swaminathan: ""Tunaheshimu wakati na juhudi za washiriki wa utafiti katika kujitolea kushiriki katika utafiti na watapokea fidia fulani, maelezo ambayo yatakaguliwa wakati wa mchakato wa idhini ya habari." Ni nani atakayepewa kipaumbele cha kwanza kwa chanjo ya COVID-19 wakati itakapokubaliwa mwishowe na itapatikanaje na kusambazwa kwa umma? "Gusmano alisema: ""Kuna maoni ya pamoja kwamba wauguzi, watu walio katika makundi ya hatari kama vile wakazi wa makao ya wazee, na wafanyakazi wengine muhimu wanapaswa kupewa kipaumbele." Lakini serikali ya shirikisho haijaweka viwango wazi na wala majimbo mengi hayajafanya hivyo. Pia hatujui kiasi cha chanjo ambazo zitagawanywa katika kila jimbo ikiwa na wakati chanjo itakapokubaliwa. """Hatujafanya mipango ya kutosha kuhusu jinsi chanjo zitakavyosafirishwa, kuhifadhiwa au kutolewa." Miongozo ya Kituo cha Kudhibiti na Kuzuia Magonjwa ni isiyo wazi juu ya mambo haya yote, na kuna haja ya kufanya kazi zaidi juu ya hili kabla hatujui jinsi inavyoweza kufanya kazi.