Skip to main content
SAGE
Search form
  • 00:00

    [SAGE video][RESEARCH METHODS tutorial][Introduction to Clinical Trials for Older People]

  • 00:14

    MILES WITHAM: I'm Miles Witham.I'm Professor of Trials for Older People.I'm based at the NIHR Newcastle Biomedical ResearchCenter, which is part of the University of Newcastlein Newcastle upon Tyne Hospitals Trust.My research interest is really anythingto do with trials for older people.And we've got a particular interest

  • 00:36

    MILES WITHAM [continued]: in looking at ways to improve physical function and qualityof life in older people.But our interests span cardiovascular disease,kidney disease, dementia, and other areas as well.I'm going to talk about trials for older people this afternoonand really to explain a little bit about why older people needtrials and what's different about designing and delivering

  • 00:58

    MILES WITHAM [continued]: trials for older people.[How did you become interested in this research?]My background is as a geriatrician.I've been practicing as a geriatrician for over 20 years.And early on in my training, I combined my clinical trainingwith a research career.One of the first trials that I did was what I did for my PhD.

  • 01:21

    MILES WITHAM [continued]: And we ran a randomized controlled trial of exercisetraining for older people.And that was a fascinating experience for me.I learned a huge amount.And it really introduced me not onlyto the need for trials for older peoplebut also introduced some of the major barriers

  • 01:42

    MILES WITHAM [continued]: that we need to overcome in delivering better trialsand more trials for older people.And really over the last 20 years, much of my researchhas been about designing and delivering better trialsfor older people.[Why is it important to conduct trials involving older people?]Older people are the main users of health care in the UK

  • 02:06

    MILES WITHAM [continued]: and in most high income countries.So they are the group of people who we reallyneed trial evidence for if we're goingto deliver the interventions, and the treatments,and the diagnoses that we really need to deliverin clinical practice.But we have a problem.And that is that most trials historicallyhave either excluded older people

  • 02:26

    MILES WITHAM [continued]: or have made it very difficult for older peopleto be included in trials.And that leads to a problem for evidence-based medicine in muchof the evidence that we've generatedfrom trials in the past, we can't be sureif it applies to older people.And the reason is that older people are notidentical to younger people.And that sounds like an obvious thing to say,

  • 02:47

    MILES WITHAM [continued]: but it's worth thinking a little bit about why that is.And there are a couple of important reasons.Firstly is that older people don'tsuffer from a single disease in the waythat some younger people do.So older people have what we call multimorbidity.[multimorbidity]And typically, the person who I see in my geriatric medicineclinic will have six diagnoses and will often

  • 03:07

    MILES WITHAM [continued]: be on 15 or 20 medications.So that sort of person, when you'rebringing them into a clinical trial,their needs are very different.And the way that they respond to an interventionmay be very different as well.Older people with lots of illnessestend to get sick, which means that the drop out ratefrom trials is often much higher.

  • 03:28

    MILES WITHAM [continued]: The other important thing, though,is that older people are very different one from another.So if you take a group of younger peopleand you measure any biological measurement,then they're often quite close to each other.My blood pressure will be similar to your blood pressure.If you take a group of older peopleand you measure something like blood pressure,there'll be a huge range.So the highest blood pressure will be twice that

  • 03:49

    MILES WITHAM [continued]: of the lowest blood pressure.So this heterogeneity is a hallmark of aging.And that has important ramificationsfor how we design and deliver trials as well.We need to make sure that we bring in all of those extremesinto the trial so it's representative.But that means also that we have a lot of noise.We have wide standard deviations.

  • 04:10

    MILES WITHAM [continued]: So when we're designing a trial, weneed to account for that in making surethat the population size we're bringing into the trialis large enough.[What considerations are there when involving older peoplein trials?]The first step really is to talk with older people themselves.All good trial design starts with engaging

  • 04:33

    MILES WITHAM [continued]: potential participants.And public and patient involvement is absolutely key.So listening to older people and saying, well,what are your priorities?What older people tell us is that they don't necessarilywant to live longer.Some do but some don't.And for many older people, particularly manyolder people with a lot of illnesses,

  • 04:53

    MILES WITHAM [continued]: it's more about physical function and quality of life.Staying active, staying independent,avoiding being admitted to a care home,avoiding being dependent on other peopleto deliver care for them, and maintainingthat quality of life.So that has important knock on effects in termsof how we design trials.First of all, we need to make surethat the intervention that we're testing

  • 05:16

    MILES WITHAM [continued]: is designed to improve physical function and quality of life.It is no good having an intervention that justmakes older people live longer.But secondly, we need to measure the right outcomes.So involving older people in the selectionof outcomes for trials is equally as important.And so we need to be picking outcomes, not just simply deathor hospitalization, but outcomes that

  • 05:36

    MILES WITHAM [continued]: reflect the need to measure physical functionand quality of life.[What are the challenges of conducting trials with olderpeople?]We talked about one or two of those challenges already.And older people do get sick.And older people do die.And unpleasant as that sounds, if people are not

  • 05:60

    MILES WITHAM [continued]: dying in your trial, and you're somebody like me studying olderpeople, you're probably not lookingat the right population.So we can't avoid that.And we have to make sure that our studydesign and particularly the way we analyzethe data is able to account for that--is able to account for dropout and missing data.[dropout missing data]There are practical things as well abouthow we design and deliver trials for older people.

  • 06:22

    MILES WITHAM [continued]: If we're taking a group of peoplewho find it difficult to get out of the house, whofind it difficult to walk any distance,then we need to make life as easy as possible for them.We need to make sure that we're bringing themto appointments in taxis.We need to make sure that we're notasking them to walk for a quarter of a miledown a long hospital corridor to get to our research facility.

  • 06:44

    MILES WITHAM [continued]: We need to think about other waysof measuring those outcomes.For instance, going and measuring thingsin their own home, a home visit, using technology, wearable techto collect outcomes, or even collecting outcomes remotely.And this is where I think we have more workto do in terms of how we select those outcomesand how we collect them in practice

  • 07:06

    MILES WITHAM [continued]: but also how we use routinely collected clinical data.[using routinely collected clinical data]We've heard a lot over the last two daysat this ICTMC conference about routinely collectedclinical data.And we need to do more in terms of usingthat to collect outcomes for trialsthat involve older people.And if we can do that, we're much morelikely to be able to bring older people into trialssuccessfully, to retain older people in trials successfully,

  • 07:30

    MILES WITHAM [continued]: and get the answers that we need to actually influencethe care for older people.[What are the ethical considerations of trials witholder people?]There are some ethical considerationsthat we need to think about.But at the same time, it's importantnot to be overprotective of older people.

  • 07:50

    MILES WITHAM [continued]: Older people are adult human beings.They are independent.And they are capable of making their own decisions.In order to make those decisions though,we do have to make sure that we provide themwith the information in a way that they can understand.And often that means perhaps simple thingslike using a bigger font size on our information sheets.It means giving them enough time and space

  • 08:13

    MILES WITHAM [continued]: to think through whether they really want to participate.It means involving other people around themthat may be important to them in making that decision,such as husbands, wives, and carers.Much of that is good practice for consenting anybodyinto a trial, but they become particularly important issues,I think, when we're looking to bring older people into trials.There are some specific ethical issues

  • 08:35

    MILES WITHAM [continued]: around older people with dementiawho may or may not be able to give informed consent,depending on the severity of their dementia illness.But that brings us into the need to sometimes get consentor assent from other people.And that's where specialist knowledge is important.

  • 08:56

    MILES WITHAM [continued]: So my advice if you're thinking about doing studieswith people with dementia is to go and partner with peoplewho are used to doing it.The ethics framework for that is different.The regulatory landscape is more complex.Usually needs a specialist ethics committee to considersome of those applications.

  • 09:17

    MILES WITHAM [continued]: So I think the principles for ethics for older peopleare not dissimilar to other groups.But we do have to remember that some olderpeople are vulnerable.They are vulnerable to the abuse of power.They are vulnerable to coercion.And we need to keep that in the back of our mind whilstnot trying to wrap them in cotton wool,and protect them, and deny them the opportunities to take part

  • 09:39

    MILES WITHAM [continued]: in clinical research.[How did you overcome challenges in your own research with olderpeople?]So one of the examples I think that illustrates someof the points quite nicely is a trialcalled BICARB, which was funded by NIHR health technologyassessment board.

  • 09:60

    MILES WITHAM [continued]: We've recently completed it.I'm not going to tell you the resultstoday because they haven't been publicly published yet.But BICARB was a trial of older people with advanced kidneydisease.And one of the issues with people with advanced kidneydisease is that although it's an illness that disproportionatelyaffects older people, most of the trials

  • 10:21

    MILES WITHAM [continued]: are done in relatively young populations.And we wanted to change that.So our trial specifically targeted peopleover the age of 60, randomized them to sodium bicarbonateor to placebo, and had a two year follow up.And we were successful in finding and recruitingolder people, although it was very challenging.

  • 10:43

    MILES WITHAM [continued]: And we eventually randomized 300 people with a mean age of 75.So there were challenges in recruiting people.There were also challenges in retaining people.And BICARB is a really good exampleof a population with lots and lots of comorbid disease.Many of them became sick.Some of them started dialysis.

  • 11:04

    MILES WITHAM [continued]: And the burden of starting dialysismeant that they did not feel able to continue in the trial.So dropout rates were relatively high.[HIGH DROPOUT RATES]But we had factored that into the design of the trialand in the way that it got analyzed as well.The other thing that's noteworthy about BICARBthough is our choice of outcome measures.So most kidney disease trials look at the kidney function.

  • 11:28

    MILES WITHAM [continued]: And that's their primary outcome,or they'll we'll look at the numberof people who started kidney dialysis as a primary outcome.But we said there's more to life than your kidney functionif you're an older person with many other diseases.So we want to focus on physical function and quality of life.So this was an unusual trial in that we actually

  • 11:50

    MILES WITHAM [continued]: did make physical function measurementthe primary outcome.And quality of life was a key secondary outcome.And that's given us a very different typeof information to that which is available from other trialsin this domain.So it's not the only trial now that'sbeen completed looking at bicarbonate in kidney disease,but it is still the only trial that

  • 12:10

    MILES WITHAM [continued]: really focuses on physical function quality of life.And it's the only trial that's recruited a groupof older people in this way.So the evidence it brings to the tableis really unique and very much complementssome of the existing evidence.[Are there any tools or resources you would recommend?]

  • 12:31

    MILES WITHAM [continued]: What I would recommend is please come and talkto us at the NIHR Aging Clinical Research Network.[NIHR Aging Clinical Research Network]So I'm now the national specialty lead for the network.And we're really keen not just to supportthe delivery of trials for older people on that specialtynetwork but to help colleagues who are delivering trials

  • 12:54

    MILES WITHAM [continued]: in other specialties, say cardiology or respiratorymedicine.We've got a wealth of experience around the table thatcan help to bring older people into trials, to helpthe design of trials, select outcomes that areappropriate for older people.And I think, working together, we can pool that expertiseand make trials across a really wide range of specialties

  • 13:15

    MILES WITHAM [continued]: relevant for older people.[stock footage supplied by HelenFieldsHotelfoxtrot/shutterstock.com][JPWallet/shutterstock.com][SAGE video]nbsp;

Abstract

Miles Witham, Professor of Trials for Older People at the University of Newcastle, discusses designing and delivering clinical trials for older people, including challenges, ethical considerations, and tools or resources.

Looks like you do not have access to this content.

Introduction to Clinical Trials for Older People

Miles Witham, Professor of Trials for Older People at the University of Newcastle, discusses designing and delivering clinical trials for older people, including challenges, ethical considerations, and tools or resources.

Copy and paste the following HTML into your website