Selected Quotes to Support Each Theme

SubthemesIllustrative Quotation
Addressing pervasive inequities
 Paucity of safety and efficacy dataWe know that children’s health professionals have a background of working without an evidence base, because that is all that they could do up to now. (Researcher, research facility, network, United Kingdom)
 Knowledge disparitiesAs a doctor, people tell me just do whatever is good for me; he will not be able to understand the meaning of a clinical trial. He will say, ‘are you trying to use me as, a guinea pig or something?’…So the meaning of consent is entirely different for an illiterate patient compared with an Internet-savvy, educated one. (Researcher, trial coordinator, India)
 Volatile environmentAnd it has worsened by...the medical profession also becoming extremely defensive, because they don’t want to get into any trouble and bad media publicity if something goes wrong. But this is where actually we really are getting hurt, especially in pediatric research. (IRB, CRO, India)
The other challenge that one could face in Nigeria is the challenge of conducting studies in places where you have political skirmishes. Where there are such skirmishes, it can affect research, especially if the investigator is not experienced. (Researcher, IRB, monitor, Nigeria)
 Challenging double standardsFor a very simple regimen to treat Burkitt’s lymphoma, it was being done in Malawi...the ethics committee in Nigeria refused the protocol. Even though the drugs are cheap and affordable, it was seen as reduced efficacy than the current standard treatment in the country. (Researcher, pediatrician, Nigeria)
If I want to treat a child and it is not so much as here take this medicine. If I want to recruit them into a trial and give them the same medicine, I have to give them a 20-page information sheet and go through a vast number of hoops. There seems to be double standards which one might argue inappropriate standards for research. (Regulator, pediatrician, United Kingdom)
 Ensuring contextual relevanceResearch in a developing country, it’s like a copy/paste thing from the West…a lot of money goes into it, and we just replicate research with not many really great outcomes. (Researcher, trial coordinator, India)
I don’t do pie-in-the-sky research. I don’t have the time, to be honest. All my research, everything I prepare, and even published, has clinical relevance…are all based on clinical need. (Researcher, IRB, regulator, South Africa)
 Market-driven forcesSo in most cases those drugs are developed for adults because that is where the biggest need is. And now we have laws that require us to also study those drugs in children. And that’s great. But it doesn’t mean that we’re looking carefully to study drugs for a need for children primarily. (Researcher, pediatrician, industry sponsor, United States)
 Industry sponsorship biasWithin the physician environment, definitely industry-sponsored trials are seen as with a bit of bias and real question as to whether physicians soil themselves by getting involved with industry. (Researcher, IRB, governance, Canada)
So even a high-quality investigator-initiated study doesn’t change any market authorization for children or even lead to include other new findings if necessary, unless the pharmaceutical company who has the market authorization for this product is willing to then submit the data for regulatory approval. (Researcher, pediatrician, IRB, Finland)
 Dissuaded by prohibitive costsInvestigator-initiated trials were sometimes possible here like the neonatal trials around caffeine for apnea. But they all cost $5 million each to answer 1 question, and so there’s no more money in the public arena to sponsor trials that are that expensive. (Researcher, pediatrician, academic, Canada)
There are not a lot of rewards for the faculty who are involved, particularly when there are small numbers of patients who would be enrolled at any 1 site to warrant their spending time, very considerable time on putting through the consent forms, the contracts, the IRB approvals and then looking for the 1 or 2 patients who they may be able to involve. (Researcher, pediatrician, industry sponsor, United States)
Contending with infrastructural barriers
 Overwhelming resource constraintsYou have brilliant ideas, but the brilliant ideas at the best they end on the desktop because of the lack of funding. Because…issues relating to children tend to be culturally very last on the priority list…So where we really have the big need is how to get funding for the investigator-initiated studies. (Researcher, IRB, monitor, Nigeria)
We have turned downed studies on occasions where we didn’t have the resources to carry them out. (Researcher, IRB, South Africa)
 Dearth of pediatric trial expertiseI can’t tell you the number of meetings that I have been in where someone said GCP and somebody goes, ‘what’s that?’ ‘Good Clinical Practice.’ First of all, we have no real sticks, we have possibly some carrots but we’re sort of neutral on ensuring in a satisfactory fashion that investigators and their staff are qualified and sufficiently maintained skills to carry out trials. (Researcher, IRB, governance, Canada)
When companies submit proposals for pediatric clinical trials for regulatory approval, they don’t get an answer. Because nobody is really able to assess the appropriateness of the study. (Researcher, pediatrician, IRB, Finland)
They are not robust so the science behind what gets submitted is sometimes not good quality; so, people often have not thought about…sample size calculations, recruitment, the feasibility of the study and…the practicalities of actually conducting the trials. (Researcher, pediatrician, IRB, Australia)
 Traversing logistical complexitiesWe have some issues such as electricity or power supply which is not very regular, and storage facilities to keep specimens are a challenge because of erratic power supply. And therefore if you are going to conduct clinical trials here, you would need an alternative source of power to ensure that biospecimens and other items are kept properly. (Researcher, Nigeria)
So if you need to get samples for central review or for collaborative studies they have to arrive within 24 to 48 hours. That can be logistically impossible from Australia. (Trial coordinator, trial center, Australia)
Navigating complex regulatory and ethical frameworks
 “Draconian” oversightSome of the regulations around that are quite stringent and that we can’t follow to the letter at the moment because it’s just impractical. For instance, it says the Minister has to provide consent for every child that participates in a study. (Researcher, pediatrician, South Africa)
I mean the 17-page sort of consent forms outlining every conceivable risk is counterproductive to good clinical practice, it’s counterproductive to good science, it’s counterproductive to moving things forward and making things better for everyone. (Researcher, regulator, government sponsor, Australia)
 Ambiguous requirementsOne area of uncertainty seems to be the definitions of key terms such as minimal risk and minor increase over minimal risk, in the pediatric context. (Regulator, IRB, governance, United States)
There are certain South American countries that just won’t allow research with a placebo, and there are countries right next door that do. So it’s whatever the local laws and regulations govern. (Researcher, pediatrician, industry sponsor, United States)
 Fear of exploiting the vulnerableIn a developing world context, there’s a greater potential for exploitation and because in a way they’re a vulnerable population; socioeconomically, they’re vulnerable, from a point of view of levels and standards of education they’re vulnerable, from a point of view of access to care their vulnerable…the reduced capacity for authorities and ethics committee to deal with these complex issues. (Researcher, pediatrician, South Africa)
 Excessive paternalism and unwarranted exclusionIf we are convinced of…our basic research that’s Phase I, Phase II studies and that we’ve done this safely, crossed our ‘t’ and dotted our ‘i’ and you know it’s safe. I don’t think we need to go adults first and then children...all studies that are safe should be offered to children and adults. This artificial cutoff that we are going to do it in adults first then children should not exist. (Researcher, IRB, regulator, South Africa)
 Precariousness of
coercion versus volunteerismThey may offer treatment that is otherwise unreachable by the children in this area, too expensive or not present at all. It may bring equipment to the centers such as laboratory, x-ray, and ultrasound whatever is needed for the trial that remains there after the trials. But these are ethically very difficult questions. Because it is possible that this indirect benefits that benefit the whole health care system…may lead to a situation where children are then allowed to participate in…trials for reasons that are not directly for the benefit of themselves but for the benefit of the society. (Researcher, pediatrician, IRB, Finland)
Respecting uniqueness of children
 Embracing pediatric research paradigmsRegulatory agencies need to move away from a very narrow interpretation of indications in terms of pediatric studies…right now so much of it’s still based on the adult indications and the pediatric-intended indications being similar. That’s certainly not always the case; for example, sildenafil is used in adults to treat erectile dysfunction and it’s used in premature neonates for pulmonary hypertension. Certainly, those 2 indications are very different as are the populations…So we’re moving toward an assessment of effect as a way to bridge data between adults and children…And also moving away from trying to prove in some cases that the disease processes are substantially similar,…asthma is asthma, but the disease process is very different. (Researcher, pharmacologist, United States)
But now the trend has been turning. It probably started with the orphan regulations in Europe where it very quickly became clear that there are no way you can make big clinical trials in rare diseases…optimally, pediatric trials should use methods that are designed for small size clinical trials. (Researcher, pediatrician, IRB, Finland)
And it is very dangerous to have a comparator that is an unproven treatment and children are exactly in this position because many of the pediatric treatments even if they are considered current choice of treatment, have not been well documented. (Researcher, pediatrician, IRB, Finland)
 Considering child-appropriate approachesSometimes we get protocols that are not designed with children in mind so that the assessment periods are too tightly scheduled, or the number of assessments is not appropriate for children. So they’ve looked at adult studies and tried to just sort of adapt that to children by just scaling down the dose. And they haven’t really thought…kids aren’t going to come in for that many visits and they’ve got school and they’ve got exams. And they’ve got days where they just don’t feel like being poked and prodded and they’re just not going to comply. And the protocols are not always written with that flexibility that’s required for working with children in mind. (Trial coordinator, trial center, Australia)
 Facilitating family-centered empowermentIn the oncology arena, the positive aspects are that the parents are always very enthusiastic and very supportive. So, they see it as an opportunity for their child, and they’re very engaged so we don’t have problems with compliance and follow-up because the parents want to do the right thing and want to contribute. (Trial coordinator, trial center, Australia)
I think parents, children, and young people need to be at the center of research and that needs to be nurtured. When people are familiar with clinical trials terms, they can be very productive, but unless they’re supported, it can be a very bruising journey that wastes a lot of time. So there needs to be specific support for children, parents, and young people that best works with networks. (Researcher, regulator, industry consultant, United Kingdom)
Driving evidence-based child health
 Promoting research advocacyUse all international forum and collaborations to raise awareness, to show success, demonstrate projects that it is feasible and that it is ethical and it is safe for the participant to be in a clinical trial…maybe using international platforms such as WHO, maybe others to engage more children, families, clinicians and researchers across the world. (Researcher, pediatrician, academic, Canada)
 Creating and seizing opportunitiesThe most feasible way today would be in the form of building infrastructure where you can have networks with people who are full-time professionals assisting in the local running of the clinical trials. (Researcher, pediatrician, IRB, Finland)
They have been very successful because of a top-down funding model by the NHS (National Health Service) to get the Medicines for Children Research Network going. And they have accomplished a lot of success. (Researcher, pediatrician, academic, Canada)
 Supporting best practiceUp to 80% or 90% of pediatric clinical trials are at an uncertain or high risk of bias when it to comes to randomization sequence, allocation concealment, blinding of the intervention of the outcome measurers, attrition, and second outcome reporting. So bias is a big threat to the validity and inefficiency and impact of trials, and so we need to start reducing research waste. (Researcher, pediatrician, academic, Canada)
All research should be demand-driven, by people who live and work in those countries, by Ministries of Health, by institutions of academia or science in those countries. I’ve seen it a lot, but I don’t believe that outside institutions should come and just set up trials with minimal collaboration… there needs to be very good…nontrial evidence, epidemiologic evidence showing the burden of the problem. (Researcher, pediatrician, DSMB, Papua New Guinea)
 Improving access to treatmentIt …would be unethical not to study the medicines in the children of resource-limited country if they need the medicines and if they are used anyway. (Researcher, pediatrician, IRB, Finland)
If it was performance indicator of a CEO of a hospital or other things, that would be seen it was desirable that people involve in clinical trials. Funding would flow to it in a way that it doesn’t now…it needs to be embedded more at the center of clinical care. (Trial coordinator, IRB, government sponsor, Australia)
 Prioritizing research productivityMore trials to do with targeting where the burden of disease is. It’s always a balancing act. Pediatrics has its fair share of rare diseases in terms of genetic disorders and other things that only occur in children. You wouldn’t want to see all the resourcing going toward diseases like diarrhea management, middle ear infection. (Trial coordinator, IRB, government sponsor, Australia)
Pooling of resources, making sure resources are not focused in rich countries. They need to be universally available…Sexy things get the funding…where they can get publicity…there needs to be an appraisal of what research we are doing; what bang for our buck we are getting;…We know the burden of disease…we need to prioritize the research in the right way! (Researcher, IRB, regulator, South Africa)
  • CEO, chief executive officer; CRO, contract research organization; DSMB, Data Safety Monitoring Board; IRB, institutional review board; WHO, World Health Organization.