for treatment studies in what situation would you use an n-of-1 single case study

An N of 1 trial can be successfully implemented to determine optimal treatments for patients with diseases as diverse as osteoarthritis, chronic neuropathic pain and attention deficit hyperactivity disorder.

Full Answer

What is a single case study?

Single case studies involve repeated measures, and manipulation of and independent variable.

What is an n of 1 trial?

Experiment means that it can be demonstrated. An N of 1 trial can be successfully implemented to determine optimal treatments for patients with diseases as diverse as osteoarthritis, chronic neuropathic pain and attention deficit hyperactivity disorder.

What are some examples of individual and combined N of 1 studies?

Examples of individual and combined n-of-1 studies investigating the utility of an intervention in the treatment of a disease. Disease Trials (n) Intervention (Dx) Results Ref. COPD 26 Ambulatory oxygen Reported use of oxygen is biased [71] OCTD 1 L-arginine diet L-arginine improved health [72] Brain injury NR Methylphenidate

When are single-case studies appropriate for clinical practice?

Recommendations for clinical practice: When rigorously designed, single-case studies can be particularly useful experimental designs in a variety of situations, such as when research resources are limited, studied conditions have low incidences, or when examining effects of novel or expensive interventions.

What is N 1 case study?

An N of 1 trial is a clinical trial in which a single patient is the entire trial, a single case study. A trial in which random allocation can be used to determine the order in which an experimental and a control intervention are given to a patient is an N of 1 randomized controlled trial.

When do you use N 1 trial?

N-of-1 trials are indicated whenever there is substantial uncertainty regarding the comparative effectiveness of treatments being considered for an individual patient.

Is data from N of trials useful to make clinical decisions?

To raise awareness among clinicians and epidemiologists that single-patient (n-of-1) trials are potentially useful for informing personalized treatment decisions for patients with chronic conditions.

Which type of research will study the effect of a treatment in a group of individuals who are ill with a specific disease?

Cohort studies are one of the most robust forms of medical research. They are well-suited to identifying causes of disease because they look at groups of people before they develop an illness.

What is a 1 1 randomization?

Description: Most clinical trials are randomized 1:1, with equal allocation to the control and treatment arms. While 1:1 allocation typically minimizes the trial sample size, many trials use alternative ratios (often 2:1).

When is a non inferiority trial used?

Non-inferiority trials are sometimes done when a placebo (an inactive treatment) cannot be used. These trials may show that a new treatment (such as a drug) is not worse than the active treatment being compared, and it may be safer and easier to take or cause fewer side effects.

What is case series study?

A case series (also known as a clinical series) is a type of medical research study that tracks subjects with a known exposure, such as patients who have received a similar treatment, or examines their medical records for exposure and outcome.

How do you analyze clinical trial data?

Box: Key questions to ask when assessing clinical dataWhat are the study's limitations? ... Does this apply to my patient? ... Is my patient sufficiently similar to the patients in the studies examined? ... Does the treatment have a clinically relevant benefit that outweighs the harms? ... Is another treatment better?More items...•

Is a case study an RCT?

This is a similar level of evidence to an RCT. Case studies, however, are considered a lower level of evidence (level 4) given the potential for bias that influences the outcome. For reference, an RCT can be level 1 or 2 evidence and a nonrandomized observational study is a level 3.

Which type of study contains a treatment?

An experiment study is a type of research where the variables are controlled as much as possible by the researcher. Test subjects are given a specific explanatory variable or treatment and the specific response variable is measured.

What study has a goal to determine what effect a particular treatment has on the outcome?

Designed Experimental Study - Unlike an observational study, an experimental study has the researcher purposely attempting to influence the results. The goal is to determine what effect a particular treatment has on the outcome. Researchers take measurements or surveys of the sample population.

What is a Phase 1 clinical trial?

The first step in testing a new treatment in humans. A phase I clinical trial tests the safety, side effects, best dose, and timing of a new treatment. It may also test the best way to give a new treatment (for example, by mouth, infusion into a vein, or injection) and how the treatment affects the body.

What is an N of 1 trial?

An N of 1 trial is a clinical trial in which a single patient is the entire trial, a single case study. A trial in which random allocation can be used to determine the order in which an experimental and a control intervention are given to a patient is an N of 1 randomized controlled trial. The order of experimental and control interventions can ...

Is the number of N of 1 trials increasing?

While N-of-1 trials are increasing, results of a recent systematic review found that statistical analyses in these studies would improve with more methodological and statistical rigor across all periods of the studies.

Can experimental and control interventions be fixed?

The order of experimental and control interventions can also be fixed by the researcher . This type of study has enabled practitioners to achieve experimental progress without the overwhelming work of designing a group comparison study. It can be very effective in confirming causality.

Is there a proliferation of personal experiments akin to N=1?

Recently, a proliferation of personal experiments akin to N=1 is occurring, along with some detailed reports about them. This trend has been sparked in part by the growing ease of collecting data and analysing it, and also motivated by the ability of individuals to report such data easily.

Can causality be definitively demonstrated?

But the N=1 study can also be executed in an AB quasi experimental way; this means that causality cannot be definitively demonstrated.

What is an N of 1 study?

An N-of-1 study can also be used to evaluate the effects of your digital product by providing detailed data on how the effect varies for a single person. Because of this, it can be used to inform the design of a comparative study.

What is the N of 1 trial?

In an N-of-1 trial, individuals are assigned to different options in a randomly-determined order, so they are exposed to the intervention and control on different days of the trial period (called multiple crossovers).

What are the pros and cons of N of 1?

Benefits of N-of-1 studies include: they can provide more granular data on changes in an outcome than you would get from combining outcome data across participants. they can identify individuals a product works for and does not work for. they generally require fewer participants in comparison to more traditional group-based studies.

Why do experimental studies require fewer participants?

in an experimental evaluation, each participant acts as their own control, meaning the design is more sensitive to differences in the effects of the intervention.

How many people are in a N of 1 study?

An N-of-1 study can include just one person, but typically a series of N-of-1 studies are undertaken. These can either be analysed as separate datasets, or in some cases combined statistically to provide an average effect between participants.

What is an observational evaluation?

observational (you record what you see) experimental (you compare periods when a digital product or features are provided with periods when they are not provided) This means it can be used during development (formative or iterative evaluation) to find out how to improve your product.

Is N of 1 good for health?

health condition is progressing rapidly. This means N-of-1 trials are good for interventions that are reversible (where the effect wanes over a short time), but not appropriate for interventions which have a long-lasting effect.

Why are N-of-1 trials important?

As a result, findings from n-of-1 trials may be especially useful in informing key health care decisions by patients and providers, particularly when combined with other scientific evidence. Likewise, the expansion of electronic health information technology into all areas of clinical care and the increasing recognition ...

What is n of 1?

single-patient trials), a form of prospective research in which different treatments are evaluated in an individual patient over time. The apparent simplicity of this study design has caused it to be enthusiastically touted in some research fields and yet overlooked, underutilized, misunderstood, or erroneously implemented in other fields. With the advent of comparative effectiveness research and patient-centered outcomes research, there is a renewed interest in n-of-1 trials as an important research method for generating unique scientific evidence on patient health outcomes. A core aspect of this interest is that the n-of-1 approach may overcome some important limitations of other methodologies that involve larger samples of subjects. As a result, findings from n-of-1 trials may be especially useful in informing key health care decisions by patients and providers, particularly when combined with other scientific evidence. Likewise, the expansion of electronic health information technology into all areas of clinical care and the increasing recognition that new systems may also be deployed for research and quality improvement have further driven interest in conducting more n-of-1 trials as part of a learning health care system. 1

Is N of 1 trial copyrighted?

Design and Implementation of N-of-1 Trials: A User's Guide is copyrighted by the Agency for Healthcare Research and Quality (AHRQ). The product and its contents may be used and incorporated into other materials on the following three conditions: (1) the contents are not changed in any way (including covers and front matter), (2) no fee is charged by the reproducer of the product or its contents for its use, and (3) the user obtains permission from the copyright holders identified therein for materials noted as copyrighted by others.

What is a n-of-1 trial?

One of the appealing features for the n-of-1 trial lies in its allowing the patient and clinician to devise an individualized trial with idiosyncratic treatments and outcomes run in real-world settings. As a result, n-of-1 designs may vary substantially and reflect great creativity. On the other hand, they often involve clinicians who are unfamiliar with the principles and practice of clinical trials and who may not have access to the resources common in research settings. Because many n-of-1 trials will be carried out in nonresearch medical office or outpatient clinic environments, it is important to ensure that proper experimental standards are maintained while allowing designs to remain flexible and easy to implement. One way to ensure such standards is to establish a centralized service responsible for crucial study tasks such as providing properly randomized or balanced/counterbalanced treatment sequences to the patient-clinician pair when they are designing the trial. We next discuss common clinical crossover trial standards that continue to apply in n-of-1 studies.

What are the issues of n-of-1 trials?

The issues discussed include special features of experimental design, data collection strategies, and statistical analysis. For simplicity, we will focus on the two-treatment, block pair design in which patients receive each of two treatments in every consecutive pair of periods with separate treatment assignments within each block of two periods, either randomized or in a systematic, balanced design. Extensions are straightforward to other designs such as K treatments (K > 2) assigned in blocks of size K, randomization schemes with differently sized blocks (e.g., block sizes equal to a multiple of the number of treatments), or unblocked assignment schemes, requiring no changes in the fundamental principles we outline. The basic design principles include randomization and counterbalancing, replication and blocking, the number of crossovers needed to optimize statistical power, and the choice of outcomes of interest to the patient and clinician. Analyses must contend with the scale of the outcomes (continuous, categorical, or count data), changes over time independent of treatment, carryover of treatment effects from one period into the next, (auto)correlation of measurements, premature end-of-treatment periods, and modes of inference (Bayesian or frequentist). All of these complexities exist within an experimental environment that is not nearly as carefully regulated as the usual randomized clinical trials and so require an appreciation of the special difficulties of gathering data in an n-of-1 trial.

Why are adaptive trials important?

While a fixed trial design is the norm, adaptive trial designs offer the chance to modify the design of an ongoing trial in order to make it more efficient or to fix problems that may have arisen. 5 Some adaptations occur naturally, as when a patient and clinician decide to stop a trial because one treatment appears to be more effective or end a treatment period early because of an adverse event. It is important in such circumstances that blinding be maintained if it is already part of the study design. For instance, it would not be proper to unblind a treatment period in order to stop one treatment, but not the other. Other adaptations could include extending the length of the trial to more treatment periods if treatment differences appear to be small or instigating play-the-winner designs, 6,7 in which the treatment that appears to be more effective is given more frequently. Such designs are generally easier to implement when the data are analyzed using Bayesian methods without tests of hypothesis whose properties depend on prespecified design plans. If frequentist inference (i.e., p-values) is used, sequential design with explicit stopping rules is necessary to protect the overall type I error rate. In some cases, decisions to adapt a design may arise from experience with similar patients. For the implementation of adaptive and sequential designs, it is important that these procedures be built into the informatics system to allow for automation of these design features. In order to ensure high-quality performance of the automated procedure, we recommend that these procedures should be reviewed periodically and calibrated as needed.

What is carryover in clinical trials?

Carryover, the tendency for treatment effects to linger beyond the crossover (when one treatment is stopped and the next one started), threatens the validity of the comparison between treatments in crossover studies, including n-of-1 trials. While statistical models may attempt to accommodate carryover, they rely on assumptions about the nature of the carryover that may be difficult to test or even control. In the extreme, carryover may extend throughout all or most of the next treatment period, contaminating many of the outcome measurements.

Why is n of 1 data important?

N-of-1 data offer rich possibilities for statistical analysis of individual treatment effects. The more data that are available both within and across patients, the more flexibility models have. This richness does come at the price of the need for careful model exploration and checking. Many errors can be avoided with good study design that respects standard experimental principles and minimizes the risk of complexity caused by autocorrelation, as by including washout periods to minimize carryover. Such design and modeling expertise is probably not within the realm of the average clinician and patient undertaking an n-of-1 study. Thus, it is crucial that standard protocols and analyses be available, especially in an automated and computerized format that promotes ease of use and robust designs and models.

What are the characteristics of a n-of-1 trial?

The unique design features of n-of-1 trials, including a multiple-period crossover design, multiple patient-selected outcomes, and focus on individual treatment effects, motivate statistical models for these trials. Data resemble a time series in that they are autocorrelated measurements on a single experimental unit. Unlike classic time series, however, the measurements are structured by the randomized design, and so statistical models also have features like those for longitudinal data with a time-varying covariate (the treatment condition). The main goal is to compare the observations made under the two treatment conditions, adjusting for any carryover effects, while accommodating the randomized block structure.

How to examine sequence effect?

One can examine a sequence effect by adding a variable that codes for sequence, for example, a dummy variable that equals 1 in periods where A follows B and 0 otherwise. Of course, if treatment effects are wearing off, it would not be appropriate to code every measurement in the A period with the sequence effect.

What is a case study?

Case studies often involve cases that are somehow unique or incomparable to others. Intrinsic case studies limit you to consideration of the specific instance of interest. Convenience can also be a factor—you may choose a specific case “because it's there.”.

How labor intensive is participant observation?

Just as participant observation research is relatively inexpensive, it is also highly labor intensive. This form of research requires that the researcher be present in the observed social scene. One cannot simply fly in and out, but must spend sufficient time so that the fullrange of activities in which participants engage are noted. Much participant observation depends upon chance—what happens to occur at the moment of observation—and, as a result, a significant investment of time is needed. While there is no definitive rule for the proper length of time necessary for observation, most projects require months, if not years, to complete. This, coupled with a modest requirement for capital equipment support means that, as noted, this methodology is particularly appropriate for younger scholars. This reality can mean that participant observation studies often do not have the depth of theoretical understanding that more likely characterizes the work of senior scholars.

Why are findings sharply distinct?

Often because of different perspectives upon entering the field and different experiences within the field, findings are sharply distinct. While the observations and interpretations of those observations may be compelling, one can reasonably wonder whether any set of conclusions is definitive.

How long does it take to complete an observational project?

While there is no definitive rule for the proper length of time necessary for observation, most projects require months, if not years, to complete. This, coupled with a modest requirement for capital equipment support means that, as noted, this methodology is particularly appropriate for younger scholars.

What is the purpose of case study research?

In discussing the use of case study research to develop theory , Eisenhardt (1989) suggests that as only a limited number of cases can usually be studied, the selection of cases involving extreme situations and polar types is useful where theory is emergent and the goal of the research is further refinement of theory.

What is single case design?

Single-case designs are synonymous with ABA research but should also be integrated with routine clinical practice . Performing as a scientist–practitioner demands that we evaluate the effects of our practices with the most control and rigor as possible. Single-case designs meet this standard, are adaptable to many consultation projects, and provide a solid empirical base for the recommendations made to consultees.

How effective is assertion training?

Here, baseline levels of performance of an individual are compared with performance levels of that individual during intervention. Research suggests that assertion training can be effective with a number of different types of clients in pursuit of a number of different outcomes . Programs focused on altering cognitions believed to be related to ineffective social behavior have sometimes been found to be as effective as those focused on altering overt behavior, suggesting an equivalence of effect across cognitive methods and assertion training. There are some indications that a combination of methods is most effective. However, some studies that purport to show that cognitive methods are as effective as social skills training in enhancing social skills do not include individual assessment of specific entry level skills and do not design individually tailored programs based on this assessment. This lack may underestimate the potential value of assertion training. A number of studies show that instructions alone (without modeling) are not sufficient to develop appropriate social behaviors with some clients labeled “schizophrenic.”

What is SCD research?

SCD research is a robust experimental method, providing potential solutions to problems with recruitment, limited funding for research, ethical issues of withholding intervention, individualizing of interventions and understanding of individual intervention responses.

What are the advantages and disadvantages of single case design?

A striking advantage of single case designs is that they can be used to evaluate treatments for individuals with very specifically defined characteristics. These characteristics do not need to be shared with large numbers of other patients or clients for the experiments to be valid. The applicability of the specific interventions studied to broader populations of clients will, of course, depend on the similarity of such clients to the subjects studied. An important disadvantage of single case designs is that they are only applicable in conditions in which return of the target complaints can be reliably demonstrated once the treatment has been removed. If a treatment results (or is hypothesized to result) in a change in personality or in the orientation of an individual to himself or others, then the repeated administration and withdrawal of treatment that is the hallmark of single case designs will not provide useful information. A further disadvantage is that the comparisons are all internally generated and generalization is accomplished only through assessment of multiple cases with similar individual characteristics and treatment.

Can time series designs be causally interpreted?

1. In general, the results of single-case designs, in particular, of time-series designs, cannot be causally interpreted since potentially infinitely many alternative explanations exist due to the lack of randomization. This is obvious because single-case designs are special cases of repeated-measures designs. 2.

Is it a contraindicated to stop applying a seemingly effective intervention plan?

It is not easy asking consultees to stop applying a seemingly effective intervention plan in order to conduct a reversal evaluation. Further, such evaluation is contraindicated when the goal of intervention is to eliminate self-harming, aggressive, destructive, and similar high-risk behaviors.

What are the criticisms of single case studies?

Single case study analysis has, however, been subject to a number of criticisms, the most common of which concern the inter-related issues of methodological rigour, researcher subjectivity, and external validity. With regard to the first point, the prototypical view here is that of Zeev Maoz (2002: 164-165), who suggests that “the use of the case study absolves the author from any kind of methodological considerations. Case studies have become in many cases a synonym for freeform research where anything goes”. The absence of systematic procedures for case study research is something that Yin (2009: 14-15) sees as traditionally the greatest concern due to a relative absence of methodological guidelines. As the previous section suggests, this critique seems somewhat unfair; many contemporary case study practitioners – and representing various strands of IR theory – have increasingly sought to clarify and develop their methodological techniques and epistemological grounding (Bennett and Elman, 2010: 499-500).

What is the goal of case studies?

As Tim May (2011: 226) notes, “the goal for many proponents of case studies ] is to[& overcome dichotomies between generalizing and particularizing, quantitative and qualitative, deductive and inductive techniques”. Research aims should drive methodological choices, rather than narrow and dogmatic preconceived approaches. As demonstrated above, there are various advantages to both idiographic and nomothetic single case study analyses – notably the empirically-rich, context-specific, holistic accounts that they have to offer, and their contribution to theory-building and, to a lesser extent, that of theory-testing. Furthermore, while they do possess clear limitations, any research method involves necessary trade-offs; the inherent weaknesses of any one method, however, can potentially be offset by situating them within a broader, pluralistic mixed-method research strategy. Whether or not single case studies are used in this fashion, they clearly have a great deal to offer.

What is Eckstein's case study?

Eckstein’s four other types of case study, meanwhile, promote a more nomothetic ( and positivist) usage. As described, disciplined-configurative studies were essentially about the use of pre-existing general theories, with a case acting “passively, in the main, as a receptacle for putting theories to work” (Eckstein, 1975: 136).

What was Harry Eckstein's contribution to the case study approach?

It begins however, by discussing Harry Eckstein’s seminal (1975) contribution to the potential advantages of the case study approach within the wider social sciences. Eckstein proposed a taxonomy which usefully identified what he considered to be the five most relevant types of case study.

What is the difference between most likely cases and least likely cases?

Most-likely cases, as per Eckstein above, are those in which a theory is to be considered likely to provide a good explanation if it is to have any application at all, whereas least-likely cases are ‘tough test’ ones in which the posited theory is unlikely to provide good explanation (Bennett and Elman, 2010: 505).

What is case study research?

One of the most prominent advocates of case study research, Robert Yin (2009: 14) defines it as “an empirical enquiry that investigates a contemporary phenomenon in depth and within its real-life context, especially when the boundaries between phenomenon and context are not clearly evident”. What this definition usefully captures is ...

Is case study analysis qualitative or transparadigmatic?

It is perhaps better to think of case studies as transparadigmatic; it is mistaken to assume single case study analysis to adhere exclusively to a qualitative methodology (or an interpretivist epistemology) even if it – or rather, practitioners of it – may be so inclined.

What to Use It For

• Similar to group-based designs, an N-of-1 study can be: 1. observational (you record what you see) 2. experimental (you compare periods when a digital product or features are provided with periods when they are not provided) This means it can be used during development (formative or iterative evaluation) to find out how to improve your product. It ...

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Pros

Cons

How to Carry Out An N-Of-1 Study

More Information and Resources

Preface

• Design and Implementation of N-of-1 Trials: A User’s Guide provides information on the design and implementation of n-of-1 trials (a.k.a. single-patient trials), a form of prospective research in which different treatments are evaluated in an individual patient over time. The apparent simplicity of this study design has caused it to be enthusiastic...

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Chapters in The User's Guide

Acknowledgments

Disclosures

Copyright

Citation

The Decide Methods Center N-Of-1 Guidance Panel

References

Introduction

Experimental Design

Data Collection

Statistical Models and Analytics

Conclusion

• N-of-1 data offer rich possibilities for statistical analysis of individual treatment effects. The more data that are available both within and across patients, the more flexibility models have. This richness does come at the price of the need for careful model exploration and checking. Many errors can be avoided with good study design that respect...

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References

Citation