Updated Helsinki Guidelines for Clinical Research Get Mixed Reviews.

The World Medical Association‘s newly updated “Ethical Principles for Medical Research Involving Human Subjects” are drawing considerable praise, as well as some criticisms.

The guidelines were first penned nearly a half century ago, in 1964, at a meeting of the World Medical Association in Helsinki, Finland, and have since been updated 7 times. Before this most recent update, the last time the document saw revisions was 2008.

The newest update, published online October 19 in JAMA, covers a wide range of topics organized under several headings, including:

  • Risks, Burdens and Benefits

  • Vulnerable Groups and Individuals

  • Scientific Requirements and Research Protocols

  • Research Ethics Committees

  • Privacy and Confidentiality

  • Informed Consent

  • Use of Placebos

  • Post-trial Provisions

  • Research Registration and Publication and Dissemination Results

  • Unproven Interventions in Clinical Practice

Two Viewpoints, both published in the same issue of the journal, help put the revisions in context. In some cases, the editorialists point out perceived shortcomings.

he revised document includes several subsections that give added emphasis to specific issues as well as improve readability, notes Paul Ndebele, PhD, from the Medical Research Council of Zimbabwe, Causeway, Harare, in one perspective . “By so doing, the Declaration of Helsinki is a better and more important authority at what it is aimed at achieving — providing guidance on conducting medical research involving humans.”

Since the first declaration in 1964, research oversight has improved. However, Dr. Ndebele says, improved oversight has sometimes led to an underrepresentation of certain groups in research protocols. The new version of the declaration recommends that heretofore underrepresented groups need to be more involved in clinical trials so they have a chance, along with other groups, of benefiting from successful research. “Instead of excluding groups that have been ordinarily excluded from research, such as minority groups, women, and children, researchers need to clearly justify why these groups have been excluded from research,” he writes.

In addition, he notes that the newer version is more relevant for countries with limited resources as it includes clear language that specifically addresses issues of importance in poor countries. Dr. Ndebele points to one example: “The 2013 version of the Declaration of Helsinki recommends use of unproven interventions in cases for which proven interventions do not exist, after the physician has sought expert advice as well as the patient’s informed consent.”

The 2013 version also discusses issues related to dissemination of health research information. That includes making sure that trials are registered in publicly accessible databases and that those databases include not only trials with positive results but also those with findings that are negative or inconclusive.

Dr. Ndebele emphasizes that informed consent must be a cornerstone of ethical research. The new declaration acknowledges that in some closely knit societies, gaining consent needs to involve other people than the patient, such as community leaders and significant others. “By addressing this reality, the new version is emphasizing respect for culture and community norms as part of the research process,” he writes.

The new guidelines also encourage researchers to make use of videos, vignettes, and other innovative means to explain the rationale for their studies.

Once trials are complete, it is important to give participants feedback on the results, he adds. He believes that doing so demonstrates respect for research participants and also helps demystify research.

Dr. Ndebele concedes that in recent years there has been considerable debate regarding the ethics of conducting medical research in developing countries. However, he says the 2013 update of the guidelines makes progress in addressing the issues surrounding that debate.

In the second Viewpoint, Joseph Millum, PhD, from the Department of Bioethics, Clinical Center, and the Fogarty International Center, National Institutes of Health, Bethesda, Maryland, acknowledge that the 2013 update represents progress. However, they also see a number of challenges that still need to be addressed.

For one, they say, “While the document purports to be a statement of enduring ethical principles, the nearly continuous process of revision undermines its authority.”

In addition, the 2013 document, similar to previous versions, is aimed primarily toward physicians. That is a mistake, they say, as the document offers recommendations for other health professionals, research ethics committees, sponsors, and governments, as well as editors and publishers. “It is time for the [World Medical Association] to recognize that the Declaration of Helsinki should address physicians as well as other health professionals and personnel involved in research,” they write.

Dr. Millum and colleagues add that the 2013 version’s treatment of informed consent remains inadequate. “It fails to recognize the possibility of waiving consent for some research involving competent adults, even though such research is common and widely endorsed.”

Neither does the declaration provide guidance on when it is appropriate to ask participants in studies to give broad consent for donating biological samples that could be used for wide-ranging studies in the future.

Dr. Millum and colleagues also take issue with the way the declaration treats “nonbeneficial studies,” or studies that pose risks to patients without offering compensating benefits.

Research combined with medical care is an increasingly popular way of conducting studies, note Dr. Millum and colleagues, but the declaration only allows such studies if, in the words of the declaration, “this is justified by its potential prevention, diagnostic or therapeutic value.”

In the view of Dr. Millum and colleagues, “The declaration’s lack of clear and consistent guidance regarding when net risks are acceptable creates unnecessary confusion and fuels the unfounded concern that all medical research is inherently exploitative.”

The authors further take issue with the new declaration’s protection of research participants who are vulnerable to harm in 1 or more ways, saying that the document “is confused about what constitutes appropriate protections and the appropriate means to achieve those protections.”

They concede that creating an international document to guide global research is an enormously difficult and complicated task. Hence, they say, it is not surprising that the newest version contains flaws. In spite of those flaws, however, they see the update as a step forward.

The nun teaching taekwondo to sick children.

Sister Linda Sim gave up taekwondo when she joined a convent. Years later, she’s dusted off her black belt at a Singaporean hospice to teach children recovering from cancer.

When she was much younger, Linda Sim wanted to join the army, but was told she was too small.

“Next I thought I could be a policewoman – to protect people,” she says, but she didn’t make the weight requirements for the police force, either.

Instead, she discovered taekwondo in 1971, and it seemed to fulfil her need to help other people. “If I had a black belt I thought I could be a bodyguard and protect somebody.” Within a few years, she achieved just that.

Though the sport gave her great mental strength, she didn’t find a practical use for her martial art for more than three decades.

Much to the chagrin of her parents, Sim met the Franciscan Missionaries of the Divine Motherhood, and decided to join them by becoming a Catholic nun.

“Being the only daughter, my mum was very upset when I said I would give my life to God and be a missionary,” she says. Her parents had hoped she would provide them with grandchildren.

Since the group’s headquarters were on the other side of the world in Britain, she would disappoint them further by leaving Singapore.

“I spent 17 years in England and three more in Africa, where I ran a hospital in Zimbabwe,” she says.

During her absence, a relationship developed between the Singapore Taekwondo Federation and Mount Alvernia hospital in the centre of the country.

Ming Wong, secretary general of the federation explains that an employee of the hospital thought some of its patients – young children being treated for cancer – could benefit from the sport. They were “stuck inside playing snakes and ladders”, she says, and the organisation agreed to provide training sessions for them.

Linda Sim with students

It was not until 2004, when Sim’s mother was diagnosed with Alzheimer’s disease, that she felt she had to return to Singapore.

When she saw the classes taking place, she knew she wanted to be involved. “That was what I had to leave behind in order to be a sister, and so I thought ‘now I’m reunited’,” she says.

Today she runs a weekly class for about 20 people, all of whom have brain tumours or childhood leukaemia. Most are young children, although three are now in their 20s, having trained under Sim for many years.

One of the older students, Ng Wei Hau, was diagnosed with a brain tumour at the age of 12 and given just six months to live by his doctors. “When I first met him he was in a wheelchair. When he reached 21 he was walking with a frame, when he reached 23 he had a stick, and now he walks unaided,” she says. Despite being partially deaf and blind, Wei Hau became a black belt last year under Sim’s tutelage.

“These children try to do their best however they can, despite their sickness,” says Wong. “I think because they want to live life for the fullest because they want to enjoy whatever time they have.”

The federation’s charitable work is not just limited to children from the hospital. The organisation works with children’s homes and other disadvantaged groups to offer free taekwondo classes to others who would not usually come into contact with the sport.

For Sim, religion is central to her motivation. Whereas most sisters teach religious education in quite a traditional way, she thinks the taekwondo classes allow her to lead by example instead.

“For me I can actually be a presence and a witness to God’s love without actually quoting scripture,” she says. “It gives me a lot of peace and satisfaction. It’s about evangelising without having to mention going to church.”

Elephants ‘understand human gesture’

In this brief clip of two of the trials, Professor Richard Byrne describes how the elephants got the point from the first test.

African elephants have demonstrated what appears to be an instinctive understanding of human gestures, according to UK scientists.

In a series of tests, researcher Ann Smet, of the University of St Andrews, offered the animals a choice between two identical buckets, then pointed at the one containing a hidden treat.

From the first trial, the elephants chose the correct bucket.

Animal keeper Rachel Melling describes the bond she feels with the elephants she works with and how they “respond to body language”.

The scientists worked with captive elephants at a lodge in Zimbabwe.

Prof Richard Byrne, a co-author on the research, said the elephants had been rescued from culling operations and trained for riding.

“They specifically train the elephants to respond to vocal cues. They don’t use any gestures at all,” said Prof Byrne.

“The idea is that the handler can walk behind the elephant and just tell it what to do with words.”

Despite this, the animals seemed to grasp the meaning of pointing from the outset. This makes them the only non-human animals to understand the gesture without being trained to do so.

In previous studies, Prof Byrne said, our closest primate cousins, the chimpanzees, proved to be “hopeless” at at similar task.

Ms Smet added that she had been impressed by the animals’ apparently innate understanding of the gesture.

“Of course we had hoped that the elephants would be able to learn to follow human pointing, or we wouldn’t have done the experiment in the first place,” she said.

“But it was really surprising that they didn’t seem to have to learn anything.

“It seems that understanding pointing is an ability elephants just possess naturally and they are cognitively much more like us than has been realised.”

Nature’s giants

  • African elephants are the largest living land animals
  • Until recently there was one species of elephant in Africa – but they are now classified as either forest or bush (or savannah) elephants
  • Forest elephants, as the name suggests, are found in equatorial forests and have straighter trunks and rounded ears
  • Bush elephants are more widespread, mostly south of the Sahara in a range of habitats including savannah, swamps and deserts

Prof Byrne said studying elephants helped build a map of part of the evolutionary tree that is very distant from humans.

“They’re so unrelated to us,” he told BBC News. “So if we find human-like abilities in an animal like an elephant, that hasn’t shared a common ancestor with people for more than 100 million years , we can be pretty sure that it’s evolved completely separately, by what’s called convergent evolution.”

The researchers said their findings might explain how elephants have successfully been tamed and have “historically had a close bond with humans, in spite of being potentially dangerous and unmanageable due to their great size”.

But the scientists added the results could be a hint that the animals gesture to one another in the wild with their “highly controllable trunks”.

Ms Smet told BBC News: “The next step [in our research] is to test whether when an elephant extends its trunk upwards and outwards – as they regularly do, such as when detecting a predator, this functions as a point.”