Modeling the economic outcomes of immuno-oncology drugs: alternative model frameworks to capture clinical outcomes.

BACKGROUND: Economic models in oncology are commonly based on the three-state partitioned survival model (PSM) distinguishing between progression-free and progressive states. However, the heterogeneity of responses observed in immuno-oncology (I-O) suggests that new approaches may be appropriate to reflect disease dynamics meaningfully. MATERIALS AND METHODS: This study explored the impact of incorporating immune-specific health states into economic models of I-O therapy. Two variants of the PSM and a Markov model were populated with data from one clinical trial in metastatic melanoma patients. Short-term modeled outcomes were benchmarked to the clinical trial data and a lifetime model horizon provided estimates of life years and quality adjusted life years (QALYs). RESULTS: The PSM-based models produced short-term outcomes closely matching the trial outcomes. Adding health states generated increased QALYs while providing a more granular representation of outcomes for decision making. The Markov model gave the greatest level of detail on outcomes but gave short-term results which diverged from those of the trial (overstating year 1 progression-free survival by around 60%). CONCLUSION: Increased sophistication in the representation of disease dynamics in economic models is desirable when attempting to model treatment response in I-O. However, the assumptions underlying different model structures and the availability of data for health state mapping may be important limiting factors.

Crawling versus walking infants' perception of affordances for locomotion over sloping surfaces.

14-month-old toddlers vs. 8.5-month-old crawling infants were encouraged to ascend and descend a sloping walkway (10 degrees, 20 degrees, 30 degrees, and 40 degrees). Infants in both locomotor groups overestimated their ability to ascend slopes. However, on descending trials where falling was more aversive, most toddlers switched from walking to sliding positions for safe descent, but crawlers plunged down head first and many fell at each increment. Toddlers touched and hesitated most before descending 10 degrees and 20 degrees slopes, and they explored alternative means for descent by testing out different sliding positions before leaving the starting platform. In contrast, crawlers touched and hesitated most before descending 30 degrees and 40 degrees slopes, and they never explored alternative sliding positions. In addition, we analyzed measures of locomotor skill and experience in relation to children's ability to perceive affordances. Findings indicate that children must learn to perceive affordances for locomotion over slopes and that learning may begin by fine-tuning of exploratory activity.

What does infant perception tell us about theories of perception?

The article begins with a summary of eight well-substantiated conclusions drawn from research on perception in infants that have implications for theories of perception. The following section examines several traditional and modern theories of perception in the light of these conclusions. Finally, some "big issues" that have divided perceptual and cognitive theories are discussed, with the suggestion that research on infants can help reconcile the divided camps. Research on perception in young infants not only flourishes but also presents a challenge to all theories of perception.

Detection of the traversability of surfaces by crawling and walking infants.

In four studies we investigated the perception of the affordance for traversal of a supporting surface. The surface presented was either rigid or deformable, and this property was specified either optically, haptically, or both. In Experiment 1A, crawling and walking infants were presented with two surfaces in succession: a standard surface that both looked and felt rigid and a deforming surface that both looked and felt nonrigid. Latency to initiate locomotion, duration of visual and haptic exploration, and displacement activity were coded from videotapes. Compared with the standard, the deforming surface elicited longer latency, more exploratory behavior, and more displacement in walkers, but not in crawlers, suggesting that typical mode of locomotion influences perceived traversability. These findings were replicated in Experiment 1B, in which the infant was presented with a dual walkway, forcing a choice between the two surfaces. Experiments 2, 3A and B, and 4A and B investigated the use of optical and haptic information in detecting traversability of rigid and nonrigid surfaces. Patterns of exploration varied with the information presented and differed for crawlers and walkers in the case of a deformable surface, as an affordance theory would predict.

Use of central and peripheral optical flow in stance and locomotion in young walkers.

Young walkers (up to 5 years of age) were presented with optical flow in a moving room. Flow was global or was restricted to either the center or the periphery of the visible optic array. On standing trials the response rate was greatest when peripheral flow was available. The availability of central flow had a smaller effect on standing, and the younger children showed greater response rates to frontal flow than did the older ones. There was a strong negative correlation between age and response rate for all conditions. Flow also affected stability during locomotion. Response rate was again related to the location of the available flow. It is concluded that children show the same relative sensitivity for flow in the periphery of the dynamic structure of the optic array as has been observed in adults, but that this differentiation of different areas of optical structure is not yet fully developed when children learn to stand.

Topical therapy for oropharyngeal symptoms of myasthenia gravis.

Inhibitors of acetylcholinesterase are commonly used in the treatment of myasthenia gravis. We studied a patient with mainly bulbar myasthenia gravis who did not tolerate oral pyridostigmine despite a clear clinical response. Treatment with nebulized pyridostigmine reduced her symptoms without systemic side effects. This route of therapy may benefit other patients.

Development of knowledge of visual-tactual affordances of substance.

Infants of 12 months were familiarized in the dark with an object of either a hard or an elastic (spongy) substance. Following 60 sec of manipulation, a visual preference test was given with simultaneous presentation of 2 films of identical objects, 1 moving in a pattern characteristic of a rigid object and 1 moving in a pattern characteristic of an elastic object. Infants handled the 2 substances differently in an appropriate manner and looked preferentially with more and longer first looks to the type of substance familiarized. A replication of this experiment with familiarization in the light yielded comparable results. A third experiment with 1-month-old infants allowed them to mouth objects of either a hard or a soft substance for haptic familiarization and then tested looking preferences with real objects moving rigidly or deforming. These infants looked longer at the object moving in a manner characteristic of the novel substance. The results, together, suggest that quite young infants detect intermodal invariants specifying some substances and perceive the affordance of the substance.

Detection of elasticity as an invariant property of objects by young infants.

Three-month-old infants were habituated to two different motions of deformation, presented 'live' with an object of sponge rubber. After habituation, one-third of the subjects was presented with a third deforming motion; one-third was presented with a rigid motion of the same object; and the other third was presented with a continuation of the habituation sequence. The group presented with a rigid motion dishabituated, exhibiting a sharp increase in looking time. The other two groups showed little or no increase. These results suggest that infants perceive elasticity of substance, in contrast to rigidity, as an invariant property of an object over different deforming motions.

Development of the perception of invariants: substance and shape.

Three experiments investigated the perception of substance and shape as invariant properties of objects by three-month-old infants. In experiment 1, infants were habituated to two differently shaped objects undergoing a rigid motion. After habituation of the infants, the objects were presented undergoing a different rigid motion, or undergoing a deforming motion, or undergoing the same rigid motion. Habituation was maintained to the new rigid motion, indicating that the two rigid motions were perceived as sharing an invariant property. Dishabituation, on the other hand, occurred when a deforming motion followed a rigid one. In experiment 2, infants were habituated to one shape undergoing two different rigid motions. After habituation, the shape was changed but the same two motions continued. Dishabituation occurred, compared to a group with no shape change, indicating that shape is distinguished as an invariant property over two rigid motions. In experiment 3, habituation to a shape undergoing two rigid motions was followed by a new shape presented motionless, or the same shape presented motionless. Cessation of motion did not prevent recognition of shape as invariant. Two properties of an object, substance and shape, thus appear to be detectable as invariant in an event sequence, an instance of "phenomenal doubling" at an early age.