I'd like to share with you the story of one of my patients called Celine.
Htela bih sa vama da podelim priču o jednoj mojoj pacijentkinji po imenu Selin.
Celine is a housewife and lives in a rural district of Cameroon in west Central Africa. Six years ago, at the time of her HIV diagnosis, she was recruited to participate in the clinical trial which was running in her health district at the time. When I first met Celine, a little over a year ago, she had gone for 18 months without any antiretroviral therapy, and she was very ill. She told me that she stopped coming to the clinic when the trial ended because she had no money for the bus fare and was too ill to walk the 35-kilometer distance. Now during the clinical trial, she'd been given all her antiretroviral drugs free of charge, and her transportation costs had been covered by the research funds. All of these ended once the trial was completed, leaving Celine with no alternatives. She was unable to tell me the names of the drugs she'd received during the trial, or even what the trial had been about. I didn't bother to ask her what the results of the trial were because it seemed obvious to me that she would have no clue. Yet what puzzled me most was Celine had given her informed consent to be a part of this trial, yet she clearly did not understand the implications of being a participant or what would happen to her once the trial had been completed.
Selin je domaćica i živi u ruralnom okrugu Kameruna u zapadnom delu Centralne Afrike. Pre šest godina, u vreme kad joj je otkriven HIV bila je regrutovana da učestvuje u kliničkim ispitivanjima koja su sprovođena, u to vreme, u njenom zdrastvenom okrugu. Kada sam prvi put srela Selinu, pre malo više od godinu, prošla je 18 meseci bez ikakve antiretrovirusne terapije i bila je veoma bolesna. Rekla mi je da je prestala da dolazi u bolnicu kada se ispitivanje završilo, jer nije imala novca za autobusku kartu i bila je previše bolesna da bi pešačila razdaljinu od 35 kilometara. U toku kliničkog ispitivanja, dobijala je antiretrovirusne lekove besplatno i troškovi prevoza su bili pokriveni istraživačkim fondom. Sve ovo se završilo kada je istraživanje završeno, ostavljajući Selin bez alternative. Nije mogla da mi kaže imena lekova koje je primala u toku istraživanja ili čak u vezi sa čim je istraživanje bilo. Nisam se trudila da je pitam koji su bili rezultati istraživanja, jer mi je bilo očigledno da ona to ne bi znala. Ipak, ono što me je najviše zbunjivalo bio je njen pristanak da bude deo istraživanja, iako ona očigledno nije razumjela koje su implikacije ako je učesnik ili šta će joj se desiti kada istraživanje bude gotovo.
Now, I have shared this story with you as an example of what can happen to participants in the clinical trial when it is poorly conducted. Maybe this particular trial yielded exciting results. Maybe it even got published in a high-profile scientific journal. Maybe it would inform clinicians around the world on how to improve on the clinical management of HIV patients. But it would have done so at a price to hundreds of patients who, like Celine, were left to their own devices once the research had been completed.
Podelila sam ovu priču sa vama, kao primer šta se dešava učesnicima bolničkih istraživanja kada su loše sprovedena. Možda je ovo konkretno istraživanje iznedrilo uzbudljive rezultate. Možda je čak i objavljeno u uglednom naučnom časopisu. Možda je informisalo bolnice širom sveta o tome kako da se poboljša klinički tretman prema HIV pacijentima. Ali sve bi to bilo urađeno po ceni stotina pacijenata koji su, kao Selina, bili prepušteni sami sebi, kada je istraživanje završeno.
I do not stand here today to suggest in any way that conducting HIV clinical trials in developing countries is bad. On the contrary, clinical trials are extremely useful tools, and are much needed to address the burden of disease in developing countries. However, the inequalities that exist between richer countries and developing countries in terms of funding pose a real risk for exploitation, especially in the context of externally-funded research. Sadly enough, the fact remains that a lot of the studies that are conducted in developing countries could never be authorized in the richer countries which fund the research.
Ja ne stojim ovde da kažem, na bilo koji način, da je sprovođenje HIV kliničkih istraživanja u državama u razvoju loše. Naprotiv, klinička istraživanja su veoma korisne alatke i veoma potrebna da se obrati pažnja na teret bolesti u državama u razvoju. Međutim, nejednakosti koje postoje između bogatih država i država u razvoju, u pogledu finansiranja predstavlja stvarnu opasnost za eksploataciju, posebno u kontekstu spoljno-finansiranog istraživanja. Nažalost, ostaje činjenica da dosta istraživanja koja su sprovođena u zemljama u razvoju, nisu mogla da budu odobrena u bogatijim zemljama koja finansiraju ta istraživanja.
I'm sure you must be asking yourselves what makes developing countries, especially those in sub-Saharan Africa, so attractive for these HIV clinical trials? Well, in order for a clinical trial to generate valid and widely applicable results, they need to be conducted with large numbers of study participants and preferably on a population with a high incidence of new HIV infections. Sub-Saharan Africa largely fits this description, with 22 million people living with HIV, an estimated 70 percent of the 30 million people who are infected worldwide. Also, research within the continent is a lot easier to conduct due to widespread poverty, endemic diseases and inadequate health care systems. A clinical trial that is considered to be potentially beneficial to the population is more likely to be authorized, and in the absence of good health care systems, almost any offer of medical assistance is accepted as better than nothing. Even more problematic reasons include lower risk of litigation, less rigorous ethical reviews, and populations that are willing to participate in almost any study that hints at a cure. As funding for HIV research increases in developing countries and ethical review in richer countries become more strict, you can see why this context becomes very, very attractive.
Sigurna sam da se pitate, šta čini zemlje u razvoju, pogotovu one u podsaharaskoj Africi, toliko privlačnim za HIV istraživanja? Pa, da bi klinička istraživanja proizvela validne i široko primjenjive rezultate, ona moraju biti sprovedena sa velikim brojem učesnika i poželjno, na populaciji sa velikom incidencijom novih HIV zaraženih. Podsaharaska Afrika u velikoj meri odgovara ovom opisu, sa 22 miliona ljudi koji žive sa HIV-om, što je 70 posto od 30 miliona ljudi koji su zaraženi u svetu. Takođe, istraživanje unutar kontinenta je mnogo lakše da se izvede zbog rasprostranjenog siromaštva, endemskih bolesti i neadekvatnog sistema zdrastvene zaštite. Bolničko istraživanje koje se smatra potencijalno korisnim za populaciju je verovatnije da bude odobreno, a u nedostatku dobrog sistema zdrastvene zaštite, skoro svaka ponuda medicinske pomoći je prihvatljivija nego nikakva. Još problematičniji razlozi uključuju manji rizik suđenja, manje rigorozne etičke kritike i populacije koje žele da učestvuju u bilo kojem istraživanju koje nagoveštava lek. Kako se finansiranje HIV istraživanja povećava u zemljama u razvoju i etičke kritike u bogatim zemljama postaju strožije, možete videti kako ovaj kontekst postaje veoma, veoma atraktivan.
The high prevalence of HIV drives researchers to conduct research that is sometimes scientifically acceptable but on many levels ethically questionable. How then can we ensure that, in our search for the cure, we do not take an unfair advantage of those who are already most affected by the pandemic? I invite you to consider four areas I think we can focus on in order to improve the way in which things are done.
Visok porast HIV-a tera istraživače da izvode istraživanja koja su ponekad naučno prihvatljiva, ali u mnogo pogleda etički diskutablna. Kako onda možemo osigurati to da u našim traganjima za lek, ne iskoristimo nepravednu prednost od onih koji su već najviše pogođeni pandemijom? Pozivam vas da razmotrite četiri oblasti na koje mislim da možemo da se fokusiramo u cilju unapređenja načina na koji se stvari rade.
The first of these is informed consent. Now, in order for a clinical trial to be considered ethically acceptable, participants must be given the relevant information in a way in which they can understand, and must freely consent to participate in the trial. This is especially important in developing countries, where a lot of participants consent to research because they believe it is the only way in which they can receive medical care or other benefits. Consent procedures that are used in richer countries are often inappropriate or ineffective in a lot of developing countries. For example, it is counterintuitive to have an illiterate study participant, like Celine, sign a lengthy consent form that they are unable to read, let alone understand. Local communities need to be more involved in establishing the criteria for recruiting participants in clinical trials, as well as the incentives for participation. The information in these trials needs to be given to the potential participants in linguistically and culturally acceptable formats.
Prvi od tih je informisani pristanak. Da bi kliničko istraživanje bilo razmatrano kao etički prihvatljivo, učesnicima moraju biti date važne informacije na način na koji oni mogu da razumeju i moraju slobodno pristati da učestvuju u istraživanju. Ovo je posebno bitno u zemljama u razvoju, gdje dosta učesnika prihvati istraživanje jer veruju da je to jedini način na koji oni mogu dobiti medicinsku brigu i druge pogodnosti. Procedure saglasnosti koje se koriste u bogatijm zemljama su često neprikladne ili neefikasne u dosta zemalja u razvoju. Na primer, nelogično je dati nepismenom učesniku, kao Selin, da potpiše poduži obrazac za saglasnost, koji on ne može da pročita, a kamoli razume. Lokalne zajednice moraju biti više uključene u postavljanju kriterijuma za regrutovanje učesnika u kliničkim istraživanjima, kao i kod podsticaja za učestvovanje. Informacije o ovim istraživanjima moraju biti date potencijalnim učesnicima u jezički i kulturno prihvatljivom formatu.
The second point I would like for you to consider is the standard of care that is provided to participants within any clinical trial. Now, this is subject to a lot of debate and controversy. Should the control group in the clinical trial be given the best current treatment which is available anywhere in the world? Or should they be given an alternative standard of care, such as the best current treatment available in the country in which the research is being conducted? Is it fair to evaluate a treatment regimen which may not be affordable or accessible to the study participants once the research has been completed? Now, in a situation where the best current treatment is inexpensive and simple to deliver, the answer is straightforward. However, the best current treatment available anywhere in the world is often very difficult to provide in developing countries. It is important to assess the potential risks and benefits of the standard of care which is to be provided to participants in any clinical trial, and establish one which is relevant for the context of the study and most beneficial for the participants within the study.
Sledeća stvar koju bih želela da razmotrite je standard zaštite koji je obezbeđen učesnicima kliničkih istraživanja. Ovo je predmet mnogih debata i kontraverze. Treba li kontrolnoj grupi u medicinskim istraživanjima dati trenutno najbolji tretman koji postoji bilo gde u svetu? Ili im treba dati alternativni standard brige, koje je trenutno najbolji tretman, koji je dostupan u zemlji u kojoj se istraživanje izvodi? Da li je fer proceniti režim lečenja koji nije novčano moguć ili dostupan učesnicima kada je istraživanje završeno? U situaciji gde je trenutno najbolja terapija jeftina i jednostavna za isporuku, odgovor je jasan. Međutim, trenutno najbolju dostupnu terapiju bilo gde u svetu je često veoma teško obezbediti u zemljama u razvoju. Važno je proceniti potencijalne rizike i benefite standarda brige koja je obezbeđena učesnicima u bilo kom bolničkom istraživanju i uspostaviti one koje su relevantni u kontekstu studije i najkorisniji za učesnike u istraživanju.
That brings us to the third point I want you think about: the ethical review of research. An effective system for reviewing the ethical suitability of clinical trials is primordial to safeguard participants within any clinical trial. Unfortunately, this is often lacking or inefficient in a lot of developing countries. Local governments need to set up effective systems for reviewing the ethical issues around the clinical trials which are authorized in different developing countries, and they need to do this by setting up ethical review committees that are independent of the government and research sponsors. Public accountability needs to be promoted through transparency and independent review by nongovernmental and international organizations as appropriate.
To nas dovodi do treće stvari, o kojoj želim da razmislite: etičke kritike istraživanja. Efikasan sistem za razmatranje etičke ispravnosti bolničkih istraživanja je primaran za zaštitu učesnika u okviru bilo kog istraživanja. Nažalost, ovo često nedostaje ili je neefikasno u dosta zemalja u razvoju. Lokalne vlade bi trebalo da postave efikasne sisteme za razmatranje etičkih problema oko kliničkih istraživanja koja su ovlašćena u zemljama u razvoju i moraju da urade ovo postavljajući odbore za razmatranje, koji su nezavisni od vlade i sponzora istraživanja. Javna odgovornost mora da bude promovisana kroz transparentno i nezavisno razmatranje od strane nevladinih i međunarodnih organizacija kao što priliči.
The final point I would like for you to consider tonight is what happens to participants in the clinical trial once the research has been completed. I think it is absolutely wrong for research to begin in the first place without a clear plan for what would happen to the participants once the trial has ended. Now, researchers need to make every effort to ensure that an intervention that has been shown to be beneficial during a clinical trial is accessible to the participants of the trial once the trial has been completed. In addition, they should be able to consider the possibility of introducing and maintaining effective treatments in the wider community once the trial ends. If, for any reason, they feel that this might not be possible, then I think they should have to ethically justify why the clinical trial should be conducted in the first place.
Poslednja stvar koju želim da razmotrite večeras je šta se dešava sa učesnicima kliničkog ispitivanja kada je ono završeno. Mislim da je potpuno pogrešno da istraživanje počne bez jasnog plana šta će se desiti sa učesnicima onda kada se istraživanje završi. Istraživači bi trebalo da se potrude da obezbede da je intervencija koja se pokazala korisnom tokom kliničkog ispitivanja, dostupna učesnicima istraživanja onda kada se istraživanje završi. Pored toga, trebalo bi da budu u stanju da razmotre mogućnost upoznavanja i održavanja efikasnih tretmana širim zajednicama kada se istražvanje završi. Ako, iz bilo kog razloga, oni smatraju da to ne bi bilo moguće, onda mislim da bi trebalo etički da opravdaju zašto kliničko istraživanje i treba uopšte da bude sprovedeno.
Now, fortunately for Celine, our meeting did not end in my office. I was able to get her enrolled into a free HIV treatment program closer to her home, and with a support group to help her cope. Her story has a positive ending, but there are thousands of others in similar situations who are much less fortunate.
Sada, srećom za Selin, naš sastanak se nije završio u mojoj kancelariji. Bila sam u mogućnosti da je upišem na besplatni HIV tretman bliže njenoj kući i sa grupom za podršku da joj pomogne da se izbori. Njena priča ima pozitivan kraj, ali ima na hiljade drugih u sličnim situacijama koji su mnogo manje srećni.
Although she may not know this, my encounter with Celine has completely changed the way in which I view HIV clinical trials in developing countries, and made me even more determined to be part of the movement to change the way in which things are done.
Iako možda ona ne zna ovo, moj susret sa Selin je totalno promenio način na koji sam posmatrala HIV klinička istraživanja u zemljama u razvoju i učinilo me odlučnijom da budem deo pokreta koji menja način na koji se stvari rade.
I believe that every single person listening to me tonight can be part of that change. If you are a researcher, I hold you to a higher standard of moral conscience, to remain ethical in your research, and not compromise human welfare in your search for answers. If you work for a funding agency or pharmaceutical company, I challenge you to hold your employers to fund research that is ethically sound. If you come from a developing country like myself, I urge you to hold your government to a more thorough review of the clinical trials which are authorized in your country. Yes, there is a need for us to find a cure for HIV, to find an effective vaccine for malaria, to find a diagnostic tool that works for T.B., but I believe that we owe it to those who willingly and selflessly consent to participate in these clinical trials to do this in a humane way.
Verujem da svaka osoba koja me sluša večeras može biti deo promene. Ako ste istraživači, pozivam vas na veće standarde moralne savesti, da zadržite etiku u vašim istraživanjima i ne ugrožavate dobrobit ljudi u potrazi za odgovorom. Ako radite za agencije za finansiranje ili farmaceutske kompanije, izazivam vas da navodite svoje poslodavce da finansiraju samo istraživanja koja su etički ispravna. Ako dolazite iz zemlje u razvoju kao ja, podstičem vas da navodite svoju vladu na detaljnije razmatranje kliničkih istraživanja koja su odobrena u vašoj zemlji. Da, postoji potreba da nađemo lek za HIV, da se nađe efikasnija vakcina za malariju, da se nađe dijagnostički instrument za tuberkulozu, ali ja verujem da onima koji voljno i nesebično prihvataju da učestvuju u tim kliničkim istraživanjima, dugujemo da uradimo ovo na human način.
Thank you.
Hvala vam.